143 results on '"Russell,AP"'
Search Results
2. Striated muscle activator of Rho signalling (STARS) overexpression in the mdx mouse enhances muscle functional capacity and regulates the actin cytoskeleton and oxidative phosphorylation pathways
- Author
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Sadler, KJ, Gatta, PAD, Naim, T, Wallace, MA, Lee, A, Zaw, T, Lindsay, A, Chung, RS, Bello, L, Pegoraro, E, Lamon, S, Lynch, GS, Russell, AP, Sadler, KJ, Gatta, PAD, Naim, T, Wallace, MA, Lee, A, Zaw, T, Lindsay, A, Chung, RS, Bello, L, Pegoraro, E, Lamon, S, Lynch, GS, and Russell, AP more...
- Abstract
NEW FINDINGS: What is the central question of this study? Striated muscle activator of rho signalling (STARS) is an actin-binding protein that regulates transcriptional pathways controlling muscle function, growth and myogenesis, processes that are impaired in dystrophic muscle: what is the regulation of the STARS pathway in Duchenne muscular dystrophy (DMD)? What is the main finding and its importance? Members of the STARS signalling pathway are reduced in the quadriceps of patients with DMD and in mouse models of muscular dystrophy. Overexpression of STARS in the dystrophic deficient mdx mouse model increased maximal isometric specific force and upregulated members of the actin cytoskeleton and oxidative phosphorylation pathways. Regulating STARS may be a therapeutic approach to enhance muscle health. ABSTRACT: Duchenne muscular dystrophy (DMD) is characterised by impaired cytoskeleton organisation, cytosolic calcium handling, oxidative stress and mitochondrial dysfunction. This results in progressive muscle damage, wasting and weakness and premature death. The striated muscle activator of rho signalling (STARS) is an actin-binding protein that activates the myocardin-related transcription factor-A (MRTFA)/serum response factor (SRF) transcriptional pathway, a pathway regulating cytoskeletal structure and muscle function, growth and repair. We investigated the regulation of the STARS pathway in the quadriceps muscle from patients with DMD and in the tibialis anterior (TA) muscle from the dystrophin-deficient mdx and dko (utrophin and dystrophin null) mice. Protein levels of STARS, SRF and RHOA were reduced in patients with DMD. STARS, SRF and MRTFA mRNA levels were also decreased in DMD muscle, while Stars mRNA levels were decreased in the mdx mice and Srf and Mrtfa mRNAs decreased in the dko mice. Overexpressing human STARS (hSTARS) in the TA muscles of mdx mice increased maximal isometric specific force by 13% (P < 0.05). This was not associated with changes in more...
- Published
- 2021
Catalog
3. Sustained cardiac programming by short-term juvenile exercise training in male rats
- Author
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Asif, Y, Wlodek, ME, Black, MJ, Russell, AP, Soeding, PF, Wadley, GD, Asif, Y, Wlodek, ME, Black, MJ, Russell, AP, Soeding, PF, and Wadley, GD
- Abstract
KEY POINTS: Cardiac hypertrophy following endurance-training is thought to be due to hypertrophy of existing cardiomyocytes. The benefits of endurance exercise on cardiac hypertrophy are generally thought to be short-lived and regress to sedentary levels within a few weeks of stopping endurance training. We have now established that cardiomyocyte hyperplasia also plays a considerable role in cardiac growth in response to just 4 weeks of endurance exercise in juvenile (5-9 weeks of age) rats. The effect of endurance exercise on cardiomyocyte hyperplasia diminishes with age and is lost by adulthood. We have also established that the effect of juvenile exercise on heart mass is sustained into adulthood. ABSTRACT: The aim of this study was to investigate if endurance training during juvenile life 'reprogrammes' the heart and leads to sustained improvements in the structure, function, and morphology of the adult heart. Male Wistar Kyoto rats were exercise trained 5 days week-1 for 4 weeks in either juvenile (5-9 weeks of age), adolescent (11-15 weeks of age) or adult life (20-24 weeks of age). Juvenile exercise training, when compared to 24-week-old sedentary rats, led to sustained increases in left ventricle (LV) mass (+18%; P < 0.05), wall thickness (+11%; P < 0.05), the longitudinal area of binucleated cardiomyocytes (P < 0.05), cardiomyocyte number (+36%; P < 0.05), and doubled the proportion of mononucleated cardiomyocytes (P < 0.05), with a less pronounced effect of exercise during adolescent life. Adult exercise training also increased LV mass (+11%; P < 0.05), wall thickness (+6%; P < 0.05) and the longitudinal area of binucleated cardiomyocytes (P < 0.05), despite no change in cardiomyocyte number or the proportion of mono- and binucleated cardiomyocytes. Resting cardiac function, LV chamber dimensions and fibrosis levels were not altered by juvenile or adult exercise training. At 9 weeks of age, juvenile exercise significantly reduced the expression of microRNA more...
- Published
- 2018
4. Repeatless: innovating print and pattern design with generative systems
- Author
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Russell, AP
- Abstract
Pre-digital textile printing technologies used in mass production mechanically transfer the same design repeatedly down the entire length of a substrate. The patterns they reproduce have to loop identically and cannot be altered without stopping and reconfiguring the printer. Whilst acknowledging that digital technology might eliminate the need for repeat, existing research and practice (Carlisle, 2002; Richardson, 2009; Häberle, 2011 and 2013; Schofield, 2012; McDonald, 2013; Paramanik, 2013) require a design to be completed prior to printing. It is proposed that if a dynamic pattern could be created that changed in real time, it could be streamed section by section to a digital fabric printer to produce a repeatless design of potentially infinite length. It is suggested that a generative system be used to do this, specifically a cellular automaton, coded in the Processing environment (Reas and Fry, 2007). Within it, motifs or other visual elements interact via a series of algorithms, using a grammar developed from traditional, non-digital methods of designing repeat pattern for printed textiles. The outcome is a design of any length that never repeats; furthermore the algorithms offer criteria by which the quality of the outcomes might be tested via peer review. This project is an interdisciplinary, practice-led MPhil/PhD, covering design, generative systems, computer programming and complexity. It is the particular synthesis of elements from the different areas that make this work innovative, shifting the paradigms of what pattern is and the way it can be reproduced. more...
- Published
- 2015
5. Repeatless: transforming surface pattern with generative design
- Author
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Russell, AP, Joseph, F, Smith, M, Smitheram, M, and Hamon, J
- Abstract
Much of the initial use of digital technology within the printed textile industry has focused on the particular advantages that it has over previous fabric printing methods. Examples include simplifying workflow, producing relatively cheap short runs, or allowing designers to work with photographic imagery and unlimited colour palettes. This paper firstly identifies that digital fabric printing has a fundamentally different possibility in relation to its forerunners. Formerly, printing was essentially the ability to reproduce the same image (or text) over and over again. Digital printing, however, does not have to work from static information; it can print a design that changes as it is being printed. Secondly, the research demonstrates that digital technology can provide the content with which to do this, creating a design that not only changes as it is being printed, but that never repeats. This is achieved by a generative software application. The resulting code is based on cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other. In this case, the elements are the individual motifs or other visual components and the system is the overall design. The rules that govern how the motifs arrange themselves are based on methods used by printed textile designers to ensure the eye can roam freely over a design, balancing the arrangement and scale of the motifs, for example, or the negative space between them. The degree of complexity possible with cellular automata allows the qualitative design process to be modelled with a richness that maps the skills of creating pattern into code. The output is a non-repeating design of infinite length that can be saved section by section to be streamed to a digital printer, exploiting the technology in an entirely novel fashion. Seen individually, digital design and digital printing technology present a large number of new possibilities for the printed textile industry. This paper shows a way that interdisciplinary, practice-led research can integrate them and offer a method to shift the paradigms of what pattern is and the way in which it can be reproduced. more...
- Published
- 2015
6. G-CSF does not influence C2C12 myogenesis despite receptor expression in healthy and dystrophic skeletal muscle (vol 5, 170, 2014)
- Author
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Wright, CR, Brown, EL, Della-Gatta, PA, Ward, AC, Lynch, GS, Russell, AP, Wright, CR, Brown, EL, Della-Gatta, PA, Ward, AC, Lynch, GS, and Russell, AP
- Abstract
[This corrects the article on p. 170 in vol. 5, PMID: 24822049.].
- Published
- 2017
7. Repeatless: combining science, technology and design to re-think print and pattern for the future
- Author
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Russell, AP, Harris, J, Miles, J, and Sinha, P
- Abstract
Digital technology offers a method to fundamentally change the way printed textile designs and surface patterns are created and applied. Within industry, pre-digital textile printing processes mechanically transfer the same design again and again down the entire substrate's length. The patterns they reproduce have to repeat identically and cannot be altered without stopping and reconfiguring the printer. The practice-led research in this paper firstly proposes that digital technology could allow a design to change as it is being printed. The application of dyestuff or other colour by a digital printer is controlled by data corresponding to the design. This need not be static; the printer could be receiving constantly evolving information, producing pattern that need never do the same thing twice. The second proposal is that generative systems be used to create evolving pattern. The possibility that digital fabric printing could remove the need for repeating pattern has been identified (Briggs and Bunce, 1995) and others have considered its implications on pattern design (Ujiie, 2006; Tallon, 2011; Bowles and Isaac, 2012). Within a textiles context, interactive design (Paramanik, 2013), the use of randomness to create non-repeating design (Carlisle, 2002), animated pattern (Richardson, 2007 and 2009) and tapestry-based applications (Sutton, 1981; Moallemi and Wainer, 2008) have been considered. However, in comparison with other creative industries such as architecture (Fraser, 1995) and graphics (Maeda, 2000) that have established areas of practice where generative systems produce design outcomes, the field has been relatively unexplored in textiles. In this research, a software application uses cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other (Wolfram, 1994). Here, the elements are the motifs or other individual images and the system is the overall design. The final proposal concerns the rules by which the elements interact; it is here that the traditions of printed textiles can be exploited. When designing a repeat pattern, practitioners use a number of methods to ensure that the eye can roam freely over a design, balancing the arrangement and scale of the motifs, for example, or the negative space between them (Day, 1903; Bowles and Isaac, 2012). Whilst these are generally used to disguise the repetitive structure that underlies such designs, the methods have two distinctive points of interest in this context. Firstly, they determine the compositional quality of the design. Secondly, they can be quantified to a workable degree as design rules. These rules can be used to create algorithms, which can in turn be translated into the code (in this case Processing (Reas and Fry, 2007)) that forms the generative software application. The output is a repeatless design of any length that can be saved section by section to be streamed to a digital printer for application to fabric or other substrates, exploiting the technology in an entirely novel fashion. The outcomes demonstrate a method of re-thinking print and pattern for the future, providing a new way of exploiting digital technology that is workable on an industrial scale. more...
- Published
- 2014
8. Overexpression of Striated Muscle Activator of Rho Signaling (STARS) Increases C2C12 Skeletal Muscle Cell Differentiation
- Author
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Wallace, MA, Della Gatta, PA, Mir, BA, Kowalski, GM, Kloehn, J, McConville, MJ, Russell, AP, Lamon, S, Wallace, MA, Della Gatta, PA, Mir, BA, Kowalski, GM, Kloehn, J, McConville, MJ, Russell, AP, and Lamon, S more...
- Abstract
BACKGROUND: Skeletal muscle growth and regeneration depend on the activation of satellite cells, which leads to myocyte proliferation, differentiation and fusion with existing muscle fibers. Skeletal muscle cell proliferation and differentiation are tightly coordinated by a continuum of molecular signaling pathways. The striated muscle activator of Rho signaling (STARS) is an actin binding protein that regulates the transcription of genes involved in muscle cell growth, structure and function via the stimulation of actin polymerization and activation of serum-response factor (SRF) signaling. STARS mediates cell proliferation in smooth and cardiac muscle models; however, whether STARS overexpression enhances cell proliferation and differentiation has not been investigated in skeletal muscle cells. RESULTS: We demonstrate for the first time that STARS overexpression enhances differentiation but not proliferation in C2C12 mouse skeletal muscle cells. Increased differentiation was associated with an increase in the gene levels of the myogenic differentiation markers Ckm, Ckmt2 and Myh4, the differentiation factor Igf2 and the myogenic regulatory factors (MRFs) Myf5 and Myf6. Exposing C2C12 cells to CCG-1423, a pharmacological inhibitor of SRF preventing the nuclear translocation of its co-factor MRTF-A, had no effect on myotube differentiation rate, suggesting that STARS regulates differentiation via a MRTF-A independent mechanism. CONCLUSION: These findings position STARS as an important regulator of skeletal muscle growth and regeneration. more...
- Published
- 2016
9. Repeatless: the use of digital technology to extend the possibilities of printed textile design
- Author
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Russell, AP
- Abstract
This paper describes an original, interdisciplinary model by which repeatless patterns can be generated dynamically in real time and streamed to a digital printer. The model produces designs that have a negligible probability of repeating. Their underlying structure is based on cellular automata, modeling traditional pattern design methods of arranging motifs or other design elements. The motifs within the pattern respond in real-time to each other, creating a composition of indefinite length. This is sent to a digital fabric printer as it is being generated, exploiting the technology in an entirely novel fashion. more...
- Published
- 2013
10. Repeatless: transforming surface pattern with generative design
- Author
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Joseph, F, Smith, M, Smitheram, M, Hamon, J, Russell, AP, Joseph, F, Smith, M, Smitheram, M, Hamon, J, and Russell, AP
- Abstract
Much of the initial use of digital technology within the printed textile industry has focused on the particular advantages that it has over previous fabric printing methods. Examples include simplifying workflow, producing relatively cheap short runs, or allowing designers to work with photographic imagery and unlimited colour palettes. This paper firstly identifies that digital fabric printing has a fundamentally different possibility in relation to its forerunners. Formerly, printing was essentially the ability to reproduce the same image (or text) over and over again. Digital printing, however, does not have to work from static information; it can print a design that changes as it is being printed. Secondly, the research demonstrates that digital technology can provide the content with which to do this, creating a design that not only changes as it is being printed, but that never repeats. This is achieved by a generative software application. The resulting code is based on cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other. In this case, the elements are the individual motifs or other visual components and the system is the overall design. The rules that govern how the motifs arrange themselves are based on methods used by printed textile designers to ensure the eye can roam freely over a design, balancing the arrangement and scale of the motifs, for example, or the negative space between them. The degree of complexity possible with cellular automata allows the qualitative design process to be modelled with a richness that maps the skills of creating pattern into code. The output is a non-repeating design of infinite length that can be saved section by section to be streamed to a digital printer, exploiting the technology in an entirely novel fashion. Seen individually, digital design and digital printing technology present a large number of new possibilities for the printed textile more...
- Published
- 2015
11. The CDP-Ethanolamine Pathway Regulates Skeletal Muscle Diacylglycerol Content and Mitochondrial Biogenesis without Altering Insulin Sensitivity.
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Selathurai,A, Kowalski,GM, Burch,ML, Sepulveda,P, Risis,S, Lee-Young,RS, Lamon,S, Meikle,PJ, Genders,AJ, McGee,SL, Watt,MJ, Russell,AP, Frank,M, Jackowski,S, Febbraio,MA, Bruce,CR, Selathurai,A, Kowalski,GM, Burch,ML, Sepulveda,P, Risis,S, Lee-Young,RS, Lamon,S, Meikle,PJ, Genders,AJ, McGee,SL, Watt,MJ, Russell,AP, Frank,M, Jackowski,S, Febbraio,MA, and Bruce,CR more...
- Abstract
Accumulation of diacylglycerol (DG) in muscle is thought to cause insulin resistance. DG is a precursor for phospholipids, thus phospholipid synthesis could be involved in regulating muscle DG. Little is known about the interaction between phospholipid and DG in muscle; therefore, we examined whether disrupting muscle phospholipid synthesis, specifically phosphatidylethanolamine (PtdEtn), would influence muscle DG content and insulin sensitivity. Muscle PtdEtn synthesis was disrupted by deleting CTP:phosphoethanolamine cytidylyltransferase (ECT), the rate-limiting enzyme in the CDP-ethanolamine pathway, a major route for PtdEtn production. While PtdEtn was reduced in muscle-specific ECT knockout mice, intramyocellular and membrane-associated DG was markedly increased. Importantly, however, this was not associated with insulin resistance. Unexpectedly, mitochondrial biogenesis and muscle oxidative capacity were increased in muscle-specific ECT knockout mice and were accompanied by enhanced exercise performance. These findings highlight the importance of the CDP-ethanolamine pathway in regulating muscle DG content and challenge the DG-induced insulin resistance hypothesis. more...
- Published
- 2015
12. Predictors and risks of body fat profiles in young New Zealand European, Māori and Pacific women: study protocol for the women's EXPLORE study.
- Author
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Kruger,R, Shultz,SP, McNaughton,SA, Russell,AP, Firestone,RT, George,L, Beck,KL, Conlon,CA, von Hurst,PR, Breier,B, Jayasinghe,SN, O'Brien,WJ, Jones,B, Stonehouse,W, Kruger,R, Shultz,SP, McNaughton,SA, Russell,AP, Firestone,RT, George,L, Beck,KL, Conlon,CA, von Hurst,PR, Breier,B, Jayasinghe,SN, O'Brien,WJ, Jones,B, and Stonehouse,W more...
- Abstract
Body mass index (BMI) (kg/m(2)) is used internationally to assess body mass or adiposity. However, BMI does not discriminate body fat content or distribution and may vary among ethnicities. Many women with normal BMI are considered healthy, but may have an unidentified "hidden fat" profile associated with higher metabolic disease risk. If only BMI is used to indicate healthy body size, it may fail to predict underlying risks of diseases of lifestyle among population subgroups with normal BMI and different adiposity levels or distributions. Higher body fat levels are often attributed to excessive dietary intake and/or inadequate physical activity. These environmental influences regulate genes and proteins that alter energy expenditure/storage. Micro ribonucleic acid (miRNAs) can influence these genes and proteins, are sensitive to diet and exercise and may influence the varied metabolic responses observed between individuals. The study aims are to investigate associations between different body fat profiles and metabolic disease risk; dietary and physical activity patterns as predictors of body fat profiles; and whether these risk factors are associated with the expression of microRNAs related to energy expenditure or fat storage in young New Zealand women. Given the rising prevalence of obesity globally, this research will address a unique gap of knowledge in obesity research. more...
- Published
- 2015
13. Exercise in the fasted state facilitates fibre type-specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans
- Author
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De Bock, Katrien, Richter, EA, Russell, AP, Eijnde, BO, Derave, Wim, Ramaekers, M, Koninckx, Erwin, Léger, B, Verhaeghe, Johan, and Hespel, Peter
- Subjects
Adult ,Male ,Cross-Over Studies ,Muscle Fibers, Slow-Twitch ,Dietary Carbohydrates ,Humans ,Fasting ,Exercise ,Muscle Fibers ,Glycogen ,Triglycerides - Abstract
The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state. ispartof: Journal of Physiology-London vol:564 issue:2 pages:649-660 ispartof: location:England status: published more...
- Published
- 2005
14. Ibuprofen supplementation and its effects on NF-κB activation in skeletal muscle following resistance exercise
- Author
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Vella,L, Markworth,JF, Peake,JM, Snow,RJ, Cameron-Smith,D, Russell,AP, Vella,L, Markworth,JF, Peake,JM, Snow,RJ, Cameron-Smith,D, and Russell,AP
- Published
- 2014
15. Repeatless: combining science, technology and design to re-think print and pattern for the future
- Author
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Harris, J, Miles, J, Sinha, P, Russell, AP, Harris, J, Miles, J, Sinha, P, and Russell, AP
- Abstract
Digital technology offers a method to fundamentally change the way printed textile designs and surface patterns are created and applied. Within industry, pre-digital textile printing processes mechanically transfer the same design again and again down the entire substrate's length. The patterns they reproduce have to repeat identically and cannot be altered without stopping and reconfiguring the printer. The practice-led research in this paper firstly proposes that digital technology could allow a design to change as it is being printed. The application of dyestuff or other colour by a digital printer is controlled by data corresponding to the design. This need not be static; the printer could be receiving constantly evolving information, producing pattern that need never do the same thing twice. The second proposal is that generative systems be used to create evolving pattern. The possibility that digital fabric printing could remove the need for repeating pattern has been identified (Briggs and Bunce, 1995) and others have considered its implications on pattern design (Ujiie, 2006; Tallon, 2011; Bowles and Isaac, 2012). Within a textiles context, interactive design (Paramanik, 2013), the use of randomness to create non-repeating design (Carlisle, 2002), animated pattern (Richardson, 2007 and 2009) and tapestry-based applications (Sutton, 1981; Moallemi and Wainer, 2008) have been considered. However, in comparison with other creative industries such as architecture (Fraser, 1995) and graphics (Maeda, 2000) that have established areas of practice where generative systems produce design outcomes, the field has been relatively unexplored in textiles. In this research, a software application uses cellular automata, a method of mathematical modelling that allows the elements within a system to evolve in relation to each other (Wolfram, 1994). Here, the elements are the motifs or other individual images and the system is the overall design. The final proposal concerns t more...
- Published
- 2014
16. Ageing has no effect on the regulation of the ubiquitin proteasome-related genes and proteins following resistance exercise.
- Author
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Stefanetti,RJ, Zacharewicz,E, Della Gatta,P, Garnham,A, Russell,AP, Lamon,S, Stefanetti,RJ, Zacharewicz,E, Della Gatta,P, Garnham,A, Russell,AP, and Lamon,S
- Published
- 2014
17. EPO-receptor is present in mouse C2C12 and human primary skeletal muscle cells but EPO does not influence myogenesis.
- Author
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Lamon,S, Zacharewicz,E, Stephens,AN, Russell,AP, Lamon,S, Zacharewicz,E, Stephens,AN, and Russell,AP
- Abstract
The role and regulation of the pleiotropic cytokine erythropoietin (EPO) in skeletal muscle are controversial. EPO exerts its effects by binding its specific receptor (EPO-R), which activates intracellular signaling and gene transcription in response to internal and external stress signals. EPO is suggested to play a direct role in myogenesis via the EPO-R, but several studies have questioned the effect of EPO treatment in muscle in vitro and in vivo. The lack of certainty surrounding the use of nonspecific EPO-R antibodies contributes to the ambiguity of the field. Our study demonstrates that the EPO-R gene and protein are expressed at each stage of mouse C2C12 and human skeletal muscle cell proliferation and differentiation and validates a specific antibody for the detection of the EPO-R protein. However, in our experimental conditions, EPO treatment had no effect on mouse C2C12 and human muscle cell proliferation, differentiation, protein synthesis or EPO-R expression. While an increase in Akt and MAPK phosphorylation was observed, we demonstrate that this effect resulted from the stress caused by changing medium and not from EPO treatment. We therefore suggest that skeletal muscle EPO-R might be present in a nonfunctional form, or too lowly expressed to play a role in muscle cell function. more...
- Published
- 2014
18. Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle.
- Author
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Russell,AP, Ghobrial,L, Wright,CR, Lamon,S, Brown,EL, Kon,M, Skelton,MR, Snow,RJ, Russell,AP, Ghobrial,L, Wright,CR, Lamon,S, Brown,EL, Kon,M, Skelton,MR, and Snow,RJ
- Abstract
The present study aimed to investigate whether skeletal muscle from whole body creatine transporter (CrT; SLC6A8) knockout mice (CrT(-/y)) actually contained creatine (Cr) and if so, whether this Cr could result from an up regulation of muscle Cr biosynthesis. Gastrocnemius muscle from CrT(-/y) and wild type (CrT(+/y)) mice were analyzed for ATP, Cr, Cr phosphate (CrP), and total Cr (TCr) content. Muscle protein and gene expression of the enzymes responsible for Cr biosynthesis L-arginine:glycine amidotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) were also determined as were the rates of in vitro Cr biosynthesis. CrT(-/y) mice muscle contained measurable (22.3 ± 4.3 mmol.kg(-1) dry mass), but markedly reduced (P < 0.05) TCr levels compared with CrT(+/y) mice (125.0 ± 3.3 mmol.kg(-1) dry mass). AGAT gene and protein expression were higher (~3 fold; P < 0.05) in CrT(-/y) mice muscle, however GAMT gene and protein expression remained unchanged. The in vitro rate of Cr biosynthesis was elevated 1.5 fold (P < 0.05) in CrT(-/y) mice muscle. These data clearly demonstrate that in the absence of CrT protein, skeletal muscle has reduced, but not absent, levels of Cr. This presence of Cr may be at least partly due to an up regulation of muscle Cr biosynthesis as evidenced by an increased AGAT protein expression and in vitro Cr biosynthesis rates in CrT(-/y) mice. Of note, the up regulation of Cr biosynthesis in CrT(-/y) mice muscle was unable to fully restore Cr levels to that found in wild type muscle. more...
- Published
- 2014
19. Cellular localization and associations of the major lipolytic proteins in human skeletal muscle at rest and during exercise
- Author
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Mason,RR, Meex,RC, Russell,AP, Canny,BJ, Watt,MJ, Mason,RR, Meex,RC, Russell,AP, Canny,BJ, and Watt,MJ
- Abstract
Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis. more...
- Published
- 2014
20. Alterations in Notch signalling in skeletal muscles from mdx and dko dystrophic mice and patients with Duchenne muscular dystrophy
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Church, JE, Trieu, J, Chee, A, Naim, T, Gehrig, SM, Lamon, S, Angelini, C, Russell, AP, Lynch, GS, Church, JE, Trieu, J, Chee, A, Naim, T, Gehrig, SM, Lamon, S, Angelini, C, Russell, AP, and Lynch, GS more...
- Abstract
New Findings What is the central question of this study? The Notch signalling pathway plays an important role in muscle regeneration, and activation of the pathway has been shown to enhance muscle regeneration in aged mice. It is unknown whether Notch activation will have a similarly beneficial effect on muscle regeneration in the context of Duchenne muscular dystrophy (DMD). What is the main finding and its importance? Although expression of Notch signalling components is altered in both mouse models of DMD and in human DMD patients, activation of the Notch signalling pathway does not confer any functional benefit on muscles from dystrophic mice, suggesting that other signalling pathways may be more fruitful targets for manipulation in treating DMD. Abstract In Duchenne muscular dystrophy (DMD), muscle damage and impaired regeneration lead to progressive muscle wasting, weakness and premature death. The Notch signalling pathway represents a central regulator of gene expression and is critical for cellular proliferation, differentiation and apoptotic signalling during all stages of embryonic muscle development. Notch activation improves muscle regeneration in aged mice, but its potential to restore regeneration and function in muscular dystrophy is unknown. We performed a comprehensive examination of several genes involved in Notch signalling in muscles from dystrophin-deficient mdx and dko (utrophin- and dystrophin-null) mice and DMD patients. A reduction of Notch1 and Hes1 mRNA in tibialis anterior muscles of dko mice and quadriceps muscles of DMD patients and a reduction of Hes1 mRNA in the diaphragm of the mdx mice were observed, with other targets being inconsistent across species. Activation and inhibition of Notch signalling, followed by measures of muscle regeneration and function, were performed in the mouse models of DMD. Notch activation had no effect on functional regeneration in C57BL/10, mdx or dko mice. Notch inhibition significantly depressed the fre more...
- Published
- 2014
21. integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes
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Dominguez, E, Galmozzi, A, Chang, JW, Hsu, K-L, Pawlak, J, Li, W, Godio, C, Thomas, J, Partida, D, Niessen, S, O'Brien, PE, Russell, AP, Watt, MJ, Nomura, DK, Cravatt, BF, Saez, E, Dominguez, E, Galmozzi, A, Chang, JW, Hsu, K-L, Pawlak, J, Li, W, Godio, C, Thomas, J, Partida, D, Niessen, S, O'Brien, PE, Russell, AP, Watt, MJ, Nomura, DK, Cravatt, BF, and Saez, E more...
- Abstract
Phenotypic screening is making a comeback in drug discovery as the maturation of chemical proteomics methods has facilitated target identification for bioactive small molecules. A limitation of these approaches is that time-consuming genetic methods or other means are often required to determine the biologically relevant target (or targets) from among multiple protein-compound interactions that are typically detected. Here, we have combined phenotypic screening of a directed small-molecule library with competitive activity-based protein profiling to map and functionally characterize the targets of screening hits. Using this approach, we identify carboxylesterase 3 (Ces3, also known as Ces1d) as a primary molecular target of bioactive compounds that promote lipid storage in adipocytes. We further show that Ces3 activity is markedly elevated during adipocyte differentiation. Treatment of two mouse models of obesity-diabetes with a Ces3 inhibitor ameliorates multiple features of metabolic syndrome, illustrating the power of the described strategy to accelerate the identification and pharmacologic validation of new therapeutic targets. more...
- Published
- 2014
22. G-CSF does not influence C2C12 myogenesis despite receptor expression in healthy and dystrophic skeletal muscle
- Author
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Wright, CR, Brown, EL, Della-Gatta, PA, Ward, AC, Lynch, GS, Russell, AP, Wright, CR, Brown, EL, Della-Gatta, PA, Ward, AC, Lynch, GS, and Russell, AP
- Abstract
Granulocyte-colony stimulating factor (G-CSF) increases recovery of rodent skeletal muscles after injury, and increases muscle function in rodent models of neuromuscular disease. However, the mechanisms by which G-CSF mediates these effects are poorly understood. G-CSF acts by binding to the membrane spanning G-CSFR and activating multiple intracellular signaling pathways. Expression of the G-CSFR within the haematopoietic system is well known, but more recently it has been demonstrated to be expressed in other tissues. However, comprehensive characterization of G-CSFR expression in healthy and diseased skeletal muscle, imperative before implementing G-CSF as a therapeutic agent for skeletal muscle conditions, has been lacking. Here we show that the G-CSFR is expressed in proliferating C2C12 myoblasts, differentiated C2C12 myotubes, human primary skeletal muscle cell cultures and in mouse and human skeletal muscle. In mdx mice, a model of human Duchenne muscular dystrophy (DMD), G-CSF mRNA and protein was down-regulated in limb and diaphragm muscle, but circulating G-CSF ligand levels were elevated. G-CSFR mRNA in the muscles of mdx mice was up-regulated however steady-state levels of the protein were down-regulated. We show that G-CSF does not influence C2C12 myoblast proliferation, differentiation or phosphorylation of Akt, STAT3, and Erk1/2. Media change alone was sufficient to elicit increases in Akt, STAT3, and Erk1/2 phosphorylation in C2C12 muscle cells and suggest previous observations showing a G-CSF increase in phosphoprotein signaling be viewed with caution. These results suggest that the actions of G-CSF may require the interaction with other cytokines and growth factors in vivo, however these data provides preliminary evidence supporting the investigation of G-CSF for the management of muscular dystrophy. more...
- Published
- 2014
23. Cellular Localization and Associations of the Major Lipolytic Proteins in Human Skeletal Muscle at Rest and during Exercise
- Author
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Moro, C, Mason, RR, Meex, RCR, Russell, AP, Canny, BJ, Watt, MJ, Moro, C, Mason, RR, Meex, RCR, Russell, AP, Canny, BJ, and Watt, MJ
- Abstract
Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis. more...
- Published
- 2014
24. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy
- Author
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Gehrig, SM, van der Poel, C, Sayer, TA, Schertzer, JD, Henstridge, DC, Church, JE, Lamon, S, Russell, AP, Davies, KE, Febbraio, MA, Lynch, GS, Gehrig, SM, van der Poel, C, Sayer, TA, Schertzer, JD, Henstridge, DC, Church, JE, Lamon, S, Russell, AP, Davies, KE, Febbraio, MA, and Lynch, GS more...
- Abstract
Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies. more...
- Published
- 2012
25. Cultured muscle cells display defects of mitochondrial myopathy ameliorated by anti-oxidants.
- Author
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Vargani L, Malena A, Sabatelli P, Loro E, Cavallini L, Magalhaes P, Valente L, Bragantini F, Carrara F, Leger B, Poulton J, Russell AP, Holt IJ, Vergani, Lodovica, Malena, Adriana, Sabatelli, Patrizia, Loro, Emanuele, Cavallini, Lucia, Magalhaes, Paolo, and Valente, Lucia more...
- Abstract
The mitochondrial DNA A3243G mutation causes neuromuscular disease. To investigate the muscle-specific pathophysiology of mitochondrial disease, rhabdomyosarcoma transmitochondrial hybrid cells (cybrids) were generated that retain the capacity to differentiate to myotubes. In some cases, striated muscle-like fibres were formed after innervation with rat embryonic spinal cord. Myotubes carrying A3243G mtDNA produced more reactive oxygen species than controls, and had altered glutathione homeostasis. Moreover, A3243G mutant myotubes showed evidence of abnormal mitochondrial distribution, which was associated with down-regulation of three genes involved in mitochondrial morphology, Mfn1, Mfn2 and DRP1. Electron microscopy revealed mitochondria with ultrastructural abnormalities and paracrystalline inclusions. All these features were ameliorated by anti-oxidant treatment, with the exception of the paracrystalline inclusions. These data suggest that rhabdomyosarcoma cybrids are a valid cellular model for studying muscle-specific features of mitochondrial disease and that excess reactive oxygen species production is a significant contributor to mitochondrial dysfunction, which is amenable to anti-oxidant therapy. [ABSTRACT FROM AUTHOR] more...
- Published
- 2007
26. Geckos running with dynamic adhesion: towards integration of ecology, energetics and biomechanics.
- Author
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Higham TE and Russell AP
- Subjects
- Animals, Biomechanical Phenomena, Energy Metabolism, Adhesiveness, Ecosystem, Locomotion physiology, Lizards physiology, Running physiology
- Abstract
Morphological specializations often enable animals to deal with challenges in nature, a prime example being the adhesive system of geckos. With this, geckos can access smooth and vertical (and even inverted) areas of the habitat that most other animals cannot. However, what is known about how geckos cling stems primarily from laboratory studies of static adhesion, with an emphasis on the integumentary component of the adhesive apparatus. In reality, the system is hierarchical, with complex musculotendinous, vascular and sensory systems that are crucial for achieving attachment, modulation of attachment strength and ultimately, detachment. Experiments examining these additional components are virtually non-existent. Additionally, there is a paucity of information about the surfaces on which geckos move, how geckos move in their natural habitat and how the adhesive system is controlled during running over complex surfaces. It is unclear whether having an adhesive system reduces the energetic costs of running compared with lizards that lack the system. We propose a complimentary set of laboratory and field studies to fill major gaps in our understanding of gecko adhesion and locomotion. Key outstanding questions are: (1) How does surface structure influence locomotion? (2) How might geckos modulate adhesion through physiological mechanisms? (3) How do geckos locomote in complex natural habitats that vary in structural properties? (4) What are the underlying energetic costs of moving dynamically in nature with an adhesive system? We address these questions and generate a roadmap for future work, including the framing of testable hypotheses. The results of such studies will help us to understand the evolution of fast locomotion in small ectothermic vertebrates and the energetic costs of moving in complex habitats. In addition, they may inform the development of small adhesive robots., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2025. Published by The Company of Biologists.) more...
- Published
- 2025
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27. The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial.
- Author
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Allsopp GL, Addinsall AB, Stephenson G, Basheer F, Gatta PAD, Hoffmann SM, Russell AP, and Wright CR
- Abstract
Trial Design: Older adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest and in response to resistance training. Systemic hypoxia modulates leukocytes and cytokines, therefore this study characterized the effects of normobaric hypoxia on the leukocyte and cytokine responses of older adults to resistance training., Methods: 20 adults aged 60-70 years performed eight weeks of moderate-intensity resistance training in either normoxia or normobaric hypoxia (14.4% O
2 ), consisting of two lower body and two upper body exercises. Venous blood was drawn before and after the training intervention and flow cytometry was used to quantify resting neutrophils, lymphocytes, monocytes, eosinophils and basophils, in addition to the subsets of lymphocytes (T, B and natural killer (NK) cells). Inflammatory cytokines were also quantified; interleukin 1 beta (IL-1β), IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Acute changes in leukocytes and cytokines were also measured in the 24 h following the last training session., Results: After the intervention there was a greater concentration of resting white blood cells (p = 0.03; 20.3% higher) T cells (p = 0.008; 25.4% higher), B cells (p = 0.004; 32.6% higher), NK cells (p = 0.012; 43.9% higher) and eosinophils (p = 0.025; 30.8% higher) in hypoxia compared to normoxia, though the cytokines were unchanged. No acute effect of hypoxia was detected in the 24 h following the last training session for any leukocyte population or inflammatory cytokine (p < 0.05)., Conclusions: Hypoxic training caused higher concentrations of resting lymphocytes and eosinophils, when compared to normoxic training. Hypoxia may have an additional beneficial effect on the immunological status of older adults., Trial Registration: Australian New Zealand Clinical Trials Registry (ANZCTR)., Trial Number: ACTRN12623001046695. Registered 27/9/2023. Retrospectively registered. All protocols adhere to the COSORT guidelines., (© 2024. The Author(s).) more...- Published
- 2024
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28. The unconditioned fear response in dystrophin-deficient mice is associated with adrenal and vascular function.
- Author
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Lindsay A and Russell AP
- Subjects
- Animals, Female, Humans, Male, Mice, Aldosterone, Corticosterone, Estradiol, Estrogens, Mice, Inbred C57BL, Mice, Inbred mdx, Muscle, Skeletal metabolism, Dystrophin metabolism, Fear, Muscular Dystrophy, Duchenne genetics
- Abstract
Loss of function mutations in the gene encoding dystrophin elicits a hypersensitive fear response in mice and humans. In the dystrophin-deficient mdx mouse, this behaviour is partially protected by oestrogen, but the mechanistic basis for this protection is unknown. Here, we show that female mdx mice remain normotensive during restraint stress compared to a hypotensive and hypertensive response in male mdx and male/female wildtype mice, respectively. Partial dystrophin expression in female mdx mice (heterozygous) also elicited a hypertensive response. Ovariectomized (OVX) female mdx mice were used to explain the normotensive response to stress. OVX lowered skeletal muscle mass and lowered the adrenal mass and zona glomerulosa area (aldosterone synthesis) in female mdx mice. During a restraint stress, OVX dampened aldosterone synthesis and lowered the corticosterone:11-dehydrocorticosterone. All OVX-induced changes were restored with replacement of oestradiol, except that oestradiol lowered the zona fasciculata area of the adrenal gland, dampened corticosterone synthesis but increased cortisol synthesis. These data suggest that oestrogen partially attenuates the unconditioned fear response in mdx mice via adrenal and vascular function. It also suggests that partial dystrophin restoration in a dystrophin-deficient vertebrate is an effective approach to develop an appropriate hypertensive response to stress., (© 2023. The Author(s).) more...
- Published
- 2023
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29. The acute leukocyte and cytokine response of older adults to resistance exercise in normobaric hypoxia.
- Author
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Allsopp GL, Addinsall AB, Stephenson G, Basheer F, Gatta PAD, May Hoffmann S, Russell AP, and Wright CR
- Abstract
Ageing causes a decline in leukocyte function and blunted leukocyte responses to resistance exercise. Systemic hypoxia exposure augments the leukocyte response to resistance exercise in young adults, yet this response remains uncharacterised in older adults. This study characterised the effects of normobaric hypoxia on the acute leukocyte and inflammatory cytokine responses to resistance exercise in older adults. We recruited 20 adults aged 60-70 years to perform an acute bout of resistance exercise in normobaric hypoxia (FiO
2 14.4%; n = 10) or normoxia (FiO2 20.93%; n = 10). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% of their predicted 1-repetition maximum. Venous blood was sampled before and up to 24 hours post-exercise to quantify neutrophils, lymphocytes, monocytes, eosinophils, basophils and cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNFα). Flow cytometry was used to classify lymphocytes as T (CD4+ helper and CD8+ cytotoxic), B and NK cells, in addition to the expression of the senescence marker CD45RA on T cells. The hypoxic group showed a larger lymphocyte response over the 24 hours post-exercise compared to the normoxic group (p = 0.035). Specifically, there were greater concentrations of CD4+ T helper cells following hypoxic exercise compared to normoxia (p = 0.046). There was also a greater proportion of CD45RA+ CD4+ T helper cells, suggesting that the cells were more senescent (p = 0.044). Hypoxia did not impact any other leukocyte population or cytokine following exercise. Normobaric hypoxia increases the lymphocyte response to an acute bout of resistance exercise in older adults., Competing Interests: The authors declare no conflict of interest., (Copyright © Biology of Sport 2023.) more...- Published
- 2023
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30. Loss of skeletal muscle estrogen-related receptors leads to severe exercise intolerance.
- Author
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Wattez JS, Eury E, Hazen BC, Wade A, Chau S, Ou SC, Russell AP, Cho Y, and Kralli A
- Subjects
- Humans, Mice, Animals, Energy Metabolism, Protein Isoforms metabolism, Estrogens metabolism, Lipids, Muscle, Skeletal metabolism, Muscular Diseases
- Abstract
Objective: Skeletal muscle oxidative capacity is central to physical activity, exercise capacity and whole-body metabolism. The three estrogen-related receptors (ERRs) are regulators of oxidative metabolism in many cell types, yet their roles in skeletal muscle remain unclear. The main aim of this study was to compare the relative contributions of ERRs to oxidative capacity in glycolytic and oxidative muscle, and to determine defects associated with loss of skeletal muscle ERR function., Methods: We assessed ERR expression, generated mice lacking one or two ERRs specifically in skeletal muscle and compared the effects of ERR loss on the transcriptomes of EDL (predominantly glycolytic) and soleus (oxidative) muscles. We also determined the consequences of the loss of ERRs for exercise capacity and energy metabolism in mice with the most severe loss of ERR activity., Results: ERRs were induced in human skeletal muscle in response to an exercise bout. Mice lacking both ERRα and ERRγ (ERRα/γ dmKO) had the broadest and most dramatic disruption in skeletal muscle gene expression. The most affected pathway was "mitochondrial function", in particular Oxphos and TCA cycle genes, and transcriptional defects were more pronounced in the glycolytic EDL than the oxidative soleus. Mice lacking ERRβ and ERRγ, the two isoforms expressed highly in oxidative muscles, also exhibited defects in lipid and branch chain amino acid metabolism genes, specifically in the soleus. The pronounced disruption of oxidative metabolism in ERRα/γ dmKO mice led to pale muscles, decreased oxidative capacity, histochemical patterns reminiscent of minicore myopathies, and severe exercise intolerance, with the dmKO mice unable to switch to lipid utilization upon running. ERRα/γ dmKO mice showed no defects in whole-body glucose and energy homeostasis., Conclusions: Our findings define gene expression programs in skeletal muscle that depend on different combinations of ERRs, and establish a central role for ERRs in skeletal muscle oxidative metabolism and exercise capacity. Our data reveal a high degree of functional redundancy among muscle ERR isoforms for the protection of oxidative capacity, and show that ERR isoform-specific phenotypes are driven in part, but not exclusively, by their relative levels in different muscles., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.) more...
- Published
- 2023
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31. Ontogeny of the paraphalanges and derived phalanges of Hemidactylus turcicus (Squamata: Gekkonidae).
- Author
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Griffing AH, Gamble T, Bauer AM, and Russell AP
- Subjects
- Animals, Phylogeny, Lizards anatomy & histology
- Abstract
Gekkotan lizards of the genus Hemidactylus exhibit derived digital morphologies. These include heavily reduced antepenultimate phalanges of digits III and IV of the manus and digits III-V of the pes, as well as enigmatic cartilaginous structures called paraphalanges. Despite this well-known morphological derivation, no studies have investigated the development of these structures. We aimed to determine if heterochrony underlies the derived antepenultimate phalanges of Hemidactylus. Furthermore, we aimed to determine if convergently evolved paraphalanges exhibit similar or divergent developmental patterns. Herein we describe embryonic skeletal development in the hands and feet of four gekkonid species, exhibiting a range of digital morphologies. We determined that the derived antepenultimate phalanges of Hemidactylus are the products of paedomorphosis. Furthermore, we found divergent developmental patterns between convergently evolved paraphalanges., (© 2022 Anatomical Society.) more...
- Published
- 2022
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32. Muscle Adaptations to Heavy-Load and Blood Flow Restriction Resistance Training Methods.
- Author
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May AK, Russell AP, Della Gatta PA, and Warmington SA
- Abstract
Resistance-based blood flow restriction training (BFRT) improves skeletal muscle strength and size. Unlike heavy-load resistance training (HLRT), there is debate as to whether strength adaptations following BFRT interventions can be primarily attributed to concurrent muscle hypertrophy, as the magnitude of hypertrophy is often minor. The present study aimed to investigate the effect of 7 weeks of BFRT and HLRT on muscle strength and hypertrophy. The expression of protein growth markers from muscle biopsy samples was also measured. Male participants were allocated to moderately heavy-load training (HL; n = 9), low-load BFRT (LL + BFR; n = 8), or a control (CON; n = 9) group to control for the effect of time. HL and LL + BFR completed 21 training sessions (3 d.week
-1 ) comprising bilateral knee extension and knee flexion exercises (HL = 70% one-repetition maximum (1-RM), LL + BFR = 20% 1-RM + blood flow restriction). Bilateral knee extension and flexion 1-RM strength were assessed, and leg muscle CSA was measured via peripheral quantitative computed tomography. Protein growth markers were measured in vastus lateralis biopsy samples taken pre- and post the first and last training sessions. Biopsy samples were also taken from CON at the same time intervals as HL and LL + BFR. Knee extension 1-RM strength increased in HL (19%) and LL + BFR (19%) but not CON (2%; p < 0.05). Knee flexion 1-RM strength increased similarly between all groups, as did muscle CSA (50% femur length; HL = 2.2%, LL + BFR = 3.0%, CON = 2.1%; TIME main effects). 4E-BP1 (Thr37/46) phosphorylation was lower in HL and LL + BFR immediately post-exercise compared with CON in both sessions ( p < 0.05). Expression of other growth markers was similar between groups ( p > 0.05). Overall, BFRT and HLRT improved muscle strength and size similarly, with comparable changes in intramuscular protein growth marker expression, both acutely and chronically, suggesting the activation of similar anabolic pathways. However, the low magnitude of muscle hypertrophy was not significantly different to the non-training control suggesting that strength adaptation following 7 weeks of BFRT is not driven by hypertrophy, but rather neurological adaptation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 May, Russell, Della Gatta and Warmington.) more...- Published
- 2022
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33. miR-23a suppression accelerates functional decline in the rNLS8 mouse model of TDP-43 proteinopathy.
- Author
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Tsitkanou S, Della Gatta PA, Abbott G, Wallace MA, Lindsay A, Gerlinger-Romero F, Walker AK, Foletta VC, and Russell AP
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Amyotrophic Lateral Sclerosis metabolism, DNA-Binding Proteins genetics, MicroRNAs genetics, TDP-43 Proteinopathies genetics
- Abstract
Skeletal muscle dysfunction may contribute to the progression and severity of amyotrophic lateral sclerosis (ALS). In the present study, we characterized the skeletal muscle pathophysiology in an inducible transgenic mouse model (rNLS8) that develops a TAR-DNA binding protein (TDP-43) proteinopathy and ALS-like neuropathology and disease progression; representative of >90% of all familial and sporadic ALS cases. As we previously observed elevated levels of miR-23a in skeletal muscle of patients with familial and sporadic ALS, we also investigated the effect of miR-23a suppression on skeletal muscle pathophysiology and disease severity in rNLS8 mice. Five weeks after disease onset TDP-43 protein accumulation was observed in tibialis anterior (TA), quadriceps (QUAD) and diaphragm muscle lysates and associated with skeletal muscle atrophy. In the TA muscle TDP-43 was detected in muscle fibres that appeared atrophied and angular in appearance and that also contained β-amyloid aggregates. These fibres were also positive for neural cell adhesion molecule (NCAM), but not embryonic myosin heavy chain (eMHC), indicating TDP-43/ β-amyloid localization in denervated muscle fibres. There was an upregulation of genes associated with myogenesis and NMJ degeneration and a decrease in the MURF1 atrophy-related protein in skeletal muscle. Suppression of miR-23a impaired rotarod performance and grip strength and accelerated body weight loss during early stages of disease progression. This was associated with increased AchRα mRNA expression and decreased protein levels of PGC-1α. The TDP-43 proteinopathy-induced impairment of whole body and skeletal muscle functional performance is associated with muscle wasting and elevated myogenic and NMJ stress markers. Suppressing miR-23a in the rNLS8 mouse model of ALS contributes to an early acceleration of disease progression as measured by decline in motor function., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2022
- Full Text
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34. Ankle structure of the Tokay gecko (Gekko gecko) and its role in the deployment of the subdigital adhesive system.
- Author
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Higham TE, Zhuang M, and Russell AP
- Subjects
- Animals, Ankle, Extremities, Locomotion, Adhesives, Lizards anatomy & histology
- Abstract
The remarkable ability of geckos to adhere to smooth surfaces is often thought of in terms of external structures, including the branching setae that make contact with the surface producing van der Waals forces. Some geckos also exhibit unique movements of the distal segments of the limbs during locomotion and static clinging, including active digital hyperextension and considerable pedal rotation. During static clinging, geckos can exhibit considerable adduction/abduction of the pes while the crus and thigh remain firmly adpressed to the substratum. This decoupling of pedal adduction/abduction from ankle flexion/extension and pedal long-axis rotation is a significant departure from pedal displacements of a typical lizard lacking adhesive ability. The structure of the ankle is likely key to this decoupling, although no detailed comparison of this complex joint between pad-bearing geckos and other lizards is available. Here we compare the configuration of the mesotarsal joint of nongekkotan lizards (Iguana and Pristidactylus) with that of the Tokay gecko (Gekko gecko) using prepared skeletons, scanning electron microscopy, and micro-computed tomographic (µCT) scans. We focus on the structure of the astragalocalcaneum and the fourth distal tarsal. The mesotarsal joint exhibits a suite of modifications that are likely associated with the secondarily symmetrical pes of pad-bearing geckos. For example, the lateral process of the astragalocalcaneum is much more extensive in G. gecko compared with other lizards. The mesotarsal joint exhibits several other differences permitting dissociation of long-axis rotation of the pes from flexion-extension movement, including a reduced ventral peg on the fourth distal tarsal, an articulatory pattern dominated by a well-defined, expansive distomesial notch of the astragalocalcaneum, and an associated broad proximodorsal articulatory facet of the fourth distal tarsal. Pad-bearing geckos are capable of effectively deploying their intricate adhesive system across a broad array of body angles because of this highly modified ankle. Future research should determine whether the differences encountered in G. gecko (and their extent) apply to the Gekkota as a whole and should examine how the elements of the ankle move dynamically during locomotion across a range of taxa., (© 2021 Anatomical Society.) more...
- Published
- 2021
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35. Striated muscle activator of Rho signalling (STARS) overexpression in the mdx mouse enhances muscle functional capacity and regulates the actin cytoskeleton and oxidative phosphorylation pathways.
- Author
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Sadler KJ, Gatta PAD, Naim T, Wallace MA, Lee A, Zaw T, Lindsay A, Chung RS, Bello L, Pegoraro E, Lamon S, Lynch GS, and Russell AP
- Subjects
- Actin Cytoskeleton metabolism, Animals, Disease Models, Animal, Dystrophin genetics, Dystrophin metabolism, Humans, Mice, Mice, Inbred mdx, Microfilament Proteins, Muscle, Skeletal metabolism, Muscular Dystrophy, Duchenne genetics, Muscular Dystrophy, Duchenne metabolism, Oxidative Phosphorylation
- Abstract
New Findings: What is the central question of this study? Striated muscle activator of rho signalling (STARS) is an actin-binding protein that regulates transcriptional pathways controlling muscle function, growth and myogenesis, processes that are impaired in dystrophic muscle: what is the regulation of the STARS pathway in Duchenne muscular dystrophy (DMD)? What is the main finding and its importance? Members of the STARS signalling pathway are reduced in the quadriceps of patients with DMD and in mouse models of muscular dystrophy. Overexpression of STARS in the dystrophic deficient mdx mouse model increased maximal isometric specific force and upregulated members of the actin cytoskeleton and oxidative phosphorylation pathways. Regulating STARS may be a therapeutic approach to enhance muscle health., Abstract: Duchenne muscular dystrophy (DMD) is characterised by impaired cytoskeleton organisation, cytosolic calcium handling, oxidative stress and mitochondrial dysfunction. This results in progressive muscle damage, wasting and weakness and premature death. The striated muscle activator of rho signalling (STARS) is an actin-binding protein that activates the myocardin-related transcription factor-A (MRTFA)/serum response factor (SRF) transcriptional pathway, a pathway regulating cytoskeletal structure and muscle function, growth and repair. We investigated the regulation of the STARS pathway in the quadriceps muscle from patients with DMD and in the tibialis anterior (TA) muscle from the dystrophin-deficient mdx and dko (utrophin and dystrophin null) mice. Protein levels of STARS, SRF and RHOA were reduced in patients with DMD. STARS, SRF and MRTFA mRNA levels were also decreased in DMD muscle, while Stars mRNA levels were decreased in the mdx mice and Srf and Mrtfa mRNAs decreased in the dko mice. Overexpressing human STARS (hSTARS) in the TA muscles of mdx mice increased maximal isometric specific force by 13% (P < 0.05). This was not associated with changes in muscle mass, fibre cross-sectional area, fibre type, centralised nuclei or collagen deposition. Proteomics screening followed by pathway enrichment analysis identified that hSTARS overexpression resulted in 31 upregulated and 22 downregulated proteins belonging to the actin cytoskeleton and oxidative phosphorylation pathways. These pathways are impaired in dystrophic muscle and regulate processes that are vital for muscle function. Increasing the STARS protein in dystrophic muscle improves muscle force production, potentially via synergistic regulation of cytoskeletal structure and energy production., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.) more...
- Published
- 2021
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36. The same but different: setal arrays of anoles and geckos indicate alternative approaches to achieving similar adhesive effectiveness.
- Author
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Garner AM, Wilson MC, Wright C, Russell AP, Niewiarowski PH, and Dhinojwala A
- Subjects
- Animals, Biomechanical Phenomena, Lizards anatomy & histology, Models, Biological, Toes anatomy & histology
- Abstract
The functional morphology of squamate fibrillar adhesive systems has been extensively investigated and has indirectly and directly influenced the design of synthetic counterparts. Not surprisingly, the structure and geometry of exemplar fibrils (setae) have been the subject of the bulk of the attention in such research, although variation in setal morphology along the length of subdigital adhesive pads has been implicated to be important in the effective functioning of these systems. Adhesive setal field configuration has been described for several geckos, but that of the convergent Anolis lizards, comprised of morphologically simpler fibrils, remains largely unexplored. Here, we examine setal morphology along the proximodistal axis of the digits of Anolis equestris and compare our findings to those for a model gecko, Gekko gecko. Consistent with previous work, we found that the setae of A. equestris are generally thinner, shorter, and present at higher densities than those of G. gecko and terminate in a single spatulate tip. Contrastingly, the setae of G. gecko are hierarchically branched in structure and carry hundreds of spatulate tips. Although the splitting of contacts into multiple smaller tips is predicted to increase the adhesive performance of a fiber compared to an unbranched one, we posited that the adhesive performance of G. gecko and A. equestris would be relatively similar when the configuration of the setal fields of each was accounted for. We found that, as in geckos, setal morphology of A. equestris follows a predictable pattern along the proximodistal axis of the pad, although there are several critical differences in the configuration of the setal fields of these two groups. Most notably, the pattern of variation in setal length of A. equestris is effectively opposite to that exhibited by G. gecko. This difference in clinal variation mirrors the difference in the direction in which the setal fields of anoles and geckos are peeled from the substrate, consistent with the hypothesis that biomechanical factors are the chief determinants of these patterns of variation. Future empirical work, however, is needed to validate this. Our findings set the stage for future comparative studies investigating the functional morphology of these convergent adhesive apparatuses. Such investigations will lead to an enhanced understanding of the interactions between form, function, and environment of fibril-based biological adhesive systems., (© 2020 Anatomical Society.) more...
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- 2021
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37. Revisiting the classification of squamate adhesive setae: historical, morphological and functional perspectives.
- Author
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Garner AM and Russell AP
- Abstract
Research on gecko-based adhesion has become a truly interdisciplinary endeavour, encompassing many disciplines within the natural and physical sciences. Gecko adhesion occurs by the induction of van der Waals intermolecular (and possibly other) forces between substrata and integumentary filaments (setae) terminating in at least one spatulate tip. Gecko setae have increasingly been idealized as structures with uniform dimensions and a particular branching pattern. Approaches to developing synthetic simulacra have largely adopted such an idealized form as a foundational template. Observations of entire setal fields of geckos and anoles have, however, revealed extensive, predictable variation in setal form. Some filaments of these fields do not fulfil the morphological criteria that characterize setae and, problematically, recent authors have applied the term 'seta' to structurally simpler and likely non-adhesively competent fibrils. Herein we briefly review the history of the definition of squamate setae and propose a standardized classificatory scheme for epidermal outgrowths based on a combination of whole animal performance and morphology. Our review is by no means comprehensive of the literature regarding the form, function, and development of the adhesive setae of squamates and we do not address significant advances that have been made in many areas (e.g. cell biology of setae) that are largely tangential to their classification and identification. We contend that those who aspire to simulate the form and function of squamate setae will benefit from a fuller appreciation of the diversity of these structures, thereby assisting in the identification of features most relevant to their objectives., (© 2021 The Authors.) more...
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- 2021
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38. An obesogenic maternal environment impairs mouse growth patterns, satellite cell activation, and markers of postnatal myogenesis.
- Author
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Mikovic J, Brightwell C, Lindsay A, Wen Y, Kowalski G, Russell AP, Fry CS, and Lamon S
- Subjects
- Animals, Biomarkers analysis, Biomarkers metabolism, Female, Male, Maternal Nutritional Physiological Phenomena, Mice, Mice, Inbred C57BL, MicroRNAs genetics, MicroRNAs metabolism, Obesity etiology, Obesity physiopathology, Overnutrition complications, Overnutrition physiopathology, Pregnancy, Pregnancy Complications etiology, Pregnancy Complications physiopathology, Diet, High-Fat adverse effects, Growth and Development physiology, Muscle Development physiology, Prenatal Exposure Delayed Effects etiology, Prenatal Exposure Delayed Effects physiopathology, Satellite Cells, Skeletal Muscle physiology
- Abstract
Skeletal muscle is sensitive to environmental cues that are first present in utero. Maternal overnutrition is a model of impaired muscle development leading to structural and metabolic dysfunction in adult life. In this study, we investigated the effect of an obesogenic maternal environment on growth and postnatal myogenesis in the offspring. Male C57BL/6J mice born to chow- or high-fat-diet-fed mothers were allocated to four different groups at the end of weaning. For the following 10 wk, half of the pups were maintained on the same diet as their mother and half of the pups were switched to the other diet (chow or high-fat). At 12 wk of age, muscle injury was induced using an intramuscular injection of barium chloride. Seven days later, mice were humanely killed and muscle tissue was harvested. A high-fat maternal diet impaired offspring growth patterns and downregulated satellite cell activation and markers of postnatal myogenesis 7 days after injury without altering the number of newly synthetized fibers over the whole 7-day period. Importantly, a healthy postnatal diet could not reverse any of these effects. In addition, we demonstrated that postnatal myogenesis was associated with a diet-independent upregulation of three miRNAs, mmu-miR-31-5p, mmu-miR-136-5p, and mmu-miR-296-5p. Furthermore, in vitro analysis confirmed the role of these miRNAs in myocyte proliferation. Our findings are the first to demonstrate that maternal overnutrition impairs markers of postnatal myogenesis in the offspring and are particularly relevant to today's society where the incidence of overweight/obesity in women of childbearing age is increasing. more...
- Published
- 2020
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39. MicroRNA-99b-5p downregulates protein synthesis in human primary myotubes.
- Author
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Zacharewicz E, Kalanon M, Murphy RM, Russell AP, and Lamon S
- Subjects
- 3' Untranslated Regions genetics, Animals, Cell Proliferation genetics, Gene Expression Regulation genetics, Humans, Mechanistic Target of Rapamycin Complex 1 genetics, Mice, Myoblasts metabolism, Signal Transduction genetics, MicroRNAs genetics, Muscle Fibers, Skeletal metabolism, Protein Biosynthesis genetics, TOR Serine-Threonine Kinases genetics
- Abstract
microRNAs (miRNAs) are important regulators of cellular homeostasis and exert their effect by directly controlling protein expression. We have previously reported an age-dependent negative association between microRNA-99b (miR-99b-5p) expression and muscle protein synthesis in human muscle in vivo. Here we investigated the role of miR-99b-5p as a potential negative regulator of protein synthesis via inhibition of mammalian target for rapamycin (MTOR) signaling in human primary myocytes. Overexpressing miR-99b-5p in human primary myotubes from young and old subjects significantly decreased protein synthesis with no effect of donor age. A binding interaction between miR-99b-5p and its putative binding site within the MTOR 3'-untranslated region (UTR) was confirmed in C
2 C12 myoblasts. The observed decline in protein synthesis was, however, not associated with a suppression of the MTOR protein but of its regulatory associated protein of mTOR complex 1 (RPTOR). These results demonstrate that modulating the expression levels of a miRNA can regulate protein synthesis in human muscle cells and provide a potential mechanism for muscle wasting in vivo. more...- Published
- 2020
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40. Overexpression of NDRG2 in skeletal muscle does not ameliorate the effects of stress in vivo.
- Author
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Mir BA, Mason SA, May AK, Russell AP, and Foletta VC
- Subjects
- Animals, Chronic Disease, Disease Models, Animal, Endoplasmic Reticulum Stress, Fasting, Female, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Oxidative Stress, Signal Transduction, Superoxide Dismutase metabolism, Adaptor Proteins, Signal Transducing genetics, Muscle, Skeletal metabolism, Stress, Physiological
- Abstract
New Findings: What is the central question of this study? Do elevated levels of the stress-response protein NDRG2 protect against fasting and chronic disease in mouse skeletal muscle? What is the main finding and its importance? NDRG2 levels increased in the tibialis anterior muscle in response to fasting and the effects of motor neurone disease. No alleviation of the stress-related and proteasomal pathways, mitochondrial dysfunction or muscle mass loss was observed even with the addition of exogenous NDRG2 indicating that the increase in NDRG2 is a normal adaptive response., Abstract: Skeletal muscle mass loss and dysfunction can arise from stress, which leads to enhanced protein degradation and metabolic impairment. The expression of N-myc downstream-regulated gene 2 (NDRG2) is induced in response to different stressors and is protective against the effects of stress in some tissues and cell types. Here, we investigated the endogenous NDRG2 response to the stress of fasting and chronic disease in mice and whether exogenous NDRG2 overexpression through adeno-associated viral (AAV) treatment ameliorated the response of skeletal muscle to these conditions. Endogenous levels of NDRG2 increased in the tibialis anterior muscle in response to 24 h fasting and with the development of the motor neurone disease, amyotrophic lateral sclerosis, in SOD1
G93A transgenic mice. Despite AAV-induced overexpression and increased expression with fasting, NDRG2 was unable to protect against the activation of proteasomal and stress pathways in response to fasting. Furthermore, NDRG2 was unable to reduce muscle mass loss, mitochondrial dysfunction and elevated oxidative and endoplasmic reticulum stress levels in SOD1G93A mice. Conversely, elevated NDRG2 levels did not exacerbate these stress responses. Overall, increasing NDRG2 levels might not be a useful therapeutic strategy to alleviate stress-related disease pathologies in skeletal muscle., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.) more...- Published
- 2020
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41. Intramuscular inflammatory and resolving lipid profile responses to an acute bout of resistance exercise in men.
- Author
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Vella L, Markworth JF, Farnfield MM, Maddipati KR, Russell AP, and Cameron-Smith D
- Subjects
- Arachidonic Acids metabolism, Eicosapentaenoic Acid metabolism, Humans, Lipoxygenase metabolism, Male, Muscle, Skeletal physiology, Prostaglandins metabolism, Thromboxanes metabolism, Young Adult, Lipid Metabolism, Muscle, Skeletal metabolism, Resistance Training methods
- Abstract
Lipid mediators including classical arachidonic acid-derived eicosanoids (e.g. prostaglandins and leukotrienes) and more recently identified specialized pro-resolving-mediator metabolites of the omega-3 fatty acids play essential roles in initiation, self-limitation, and active resolution of acute inflammatory responses. In this study, we examined the bioactive lipid mediator profile of human skeletal muscle at rest and following acute resistance exercise. Twelve male subjects completed a single bout of maximal isokinetic unilateral knee extension exercise and muscle biopsies were taken from the m.vastus lateralis before and at 2, 4, and 24 h of recovery. Muscle tissue lipid mediator profile was analyzed via liquid chromatography-mass spectrometry (LC-MS)-based targeted lipidomics. At 2 h postexercise, there was an increased intramuscular abundance of cyclooxygenase (COX)-derived thromboxanes (TXB
2 : 3.33 fold) and prostaglandins (PGE2 : 2.52 fold and PGF2α : 1.77 fold). Resistance exercise also transiently increased muscle concentrations of lipoxygenase (LOX) pathway-derived leukotrienes (12-Oxo LTB4 : 1.49 fold and 20-COOH LTB4 : 2.91 fold), monohydroxy-eicosatetraenoic acids (5-HETE: 2.66 fold, 12-HETE: 2.83 fold, and 15-HETE: 1.69 fold) and monohydroxy-docosahexaenoic acids (4-HDoHE: 1.69 fold, 7-HDoHE: 1.58 fold and 14-HDoHE: 2.35 fold). Furthermore, the abundance of CYP pathway-derived epoxy- and dihydroxy-eicosatrienoic acids was increased in 2 h postexercise biopsies (5,6-EpETrE: 2.48 fold, 11,12-DiHETrE: 1.66 fold and 14,15-DiHETrE: 2.23 fold). These data reveal a range of bioactive lipid mediators as present within human skeletal muscle tissue and demonstrate that acute resistance exercise transiently stimulates the local production of both proinflammatory eicosanoids and pathway markers in specialized proresolving mediator biosynthesis circuits., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.) more...- Published
- 2019
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42. Dietary Patterns in New Zealand Women: Evaluating Differences in Body Composition and Metabolic Biomarkers.
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Jayasinghe SN, Breier BH, McNaughton SA, Russell AP, Della Gatta PA, Mason S, Stonehouse W, Walsh DCI, and Kruger R
- Subjects
- Adult, Biomarkers blood, Diet standards, Energy Intake, Female, Humans, New Zealand, Nutrients, Body Composition physiology, Diet Surveys, Food Preferences
- Abstract
The combinations of food consumed together (dietary patterns) may have a greater influence on health than nutrients or food groups consumed independently. This study investigated the relationship between dietary patterns, body composition and metabolic biomarkers of premenopausal New Zealand women from three ethnic groups. In total, 408 New Zealand European, Māori and Pacific women aged 16-45 years participated in the Women's EXPLORE (EXamining Predictors Linking Obesity Related Elements) study. Participants completed a 220-item food frequency questionnaire. Several body composition parameters and metabolic biomarkers were measured. Dietary patterns were extracted by principal component analysis and dietary pattern scores were categorised into tertiles to assess links with other measured parameters. Women with higher scores for the 'refined and processed' pattern were younger, had higher body mass index, total body fat, plasma leptin and plasma insulin ( p < 0.001), and lower plasma ghrelin levels ( p < 0.05) than women with lower scores. In addition, more Māori (51%) and Pacific (68%) women followed the 'refined and processed' pattern, while more New Zealand European women (40%) followed the 'sweet and savoury snacking' pattern. These data show that dietary pattern analysis is a useful tool to assess links between diet and metabolic health. It further reveals interesting ethnic group-specific differences in dietary pattern use. more...
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- 2019
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43. Evolution of the Gekkotan Adhesive System: Does Digit Anatomy Point to One or More Origins?
- Author
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Russell AP and Gamble T
- Subjects
- Adhesiveness, Animals, Lizards anatomy & histology, Locomotion, Phylogeny, Toes anatomy & histology, Biological Evolution, Lizards physiology, Toes physiology
- Abstract
Recently-developed, molecularly-based phylogenies of geckos have provided the basis for reassessing the number of times adhesive toe-pads have arisen within the Gekkota. At present both a single origin and multiple origin hypotheses prevail, each of which has consequences that relate to explanations about digit form and evolutionary transitions underlying the enormous variation in adhesive toe pad structure among extant, limbed geckos (pygopods lack pertinent features). These competing hypotheses result from mapping the distribution of toe pads onto a phylogenetic framework employing the simple binary expedient of whether such toe pads are present or absent. It is evident, however, that adhesive toe pads are functional complexes that consist of a suite of integrated structural components that interact to bring about adhesive contact with the substratum and release from it. We evaluated the competing hypotheses about toe pad origins using 34 features associated with digit structure (drawn from the overall form of the digits; the presence and form of adhesive scansors; the proportions and structure of the phalanges; aspects of digital muscular and tendon morphology; presence and form of paraphalangeal elements; and the presence and form of substrate compliance-enhancing structures). We mapped these onto a well-supported phylogeny to reconstruct their evolution. Nineteen of these characters proved to be informative for all extant, limbed geckos, allowing us to assess which of them exhibit co-occurrence and/or clade-specificity. We found the absence of adhesive toe pads to be the ancestral state for the extant Gekkota as a whole, and our data to be consistent with independent origins of adhesive toe pads in the Diplodactylidae, Sphaerodactylidae, Phyllodactylidae, and Gekkonidae, with a strong likelihood of multiple origins in the latter three families. These findings are consistent with recently-published evidence of the presence of adhesively-competent digits in geckos generally regarded as lacking toe pads. Based upon morphology we identify other taxa at various locations within the gekkotan tree that are promising candidates for the expression of the early phases of adhesively-assisted locomotion. Investigation of functionally transitional forms will be valuable for enhancing our understanding of what is necessary and sufficient for the transition to adhesively-assisted locomotion, and for those whose objectives are to develop simulacra of the gekkotan adhesive system for biotechnological applications., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.) more...
- Published
- 2019
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44. The Integrative Biology of Gecko Adhesion: Historical Review, Current Understanding, and Grand Challenges.
- Author
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Russell AP, Stark AY, and Higham TE
- Subjects
- Adhesiveness, Animals, Adhesives chemistry, Biomimetic Materials analysis, Extremities physiology, Lizards physiology
- Abstract
Geckos are remarkable in their ability to reversibly adhere to smooth vertical, and even inverted surfaces. However, unraveling the precise mechanisms by which geckos do this has been a long process, involving various approaches over the last two centuries. Our understanding of the principles by which gecko adhesion operates has advanced rapidly over the past 20 years and, with this knowledge, material scientists have attempted to mimic the system to create artificial adhesives. From a biological perspective, recent studies have examined the diversity in morphology, performance, and real-world use of the adhesive apparatus. However, the lack of multidisciplinarity is likely a key roadblock to gaining new insights. Our goals in this paper are to 1) present a historical review of gecko adhesion research, 2) discuss the mechanisms and morphology of the adhesive apparatus, 3) discuss the origin and performance of the system in real-world contexts, 4) discuss advancement in bio-inspired design, and 5) present grand challenges in gecko adhesion research. To continue to improve our understanding, and to more effectively employ the principles of gecko adhesion for human applications, greater intensity and scope of interdisciplinary research are necessary., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.) more...
- Published
- 2019
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45. Going Out on a Limb: How Investigation of the Anoline Adhesive System Can Enhance Our Understanding of Fibrillar Adhesion.
- Author
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Garner AM, Wilson MC, Russell AP, Dhinojwala A, and Niewiarowski PH
- Subjects
- Adhesiveness, Animals, Surface Properties, Adhesives chemistry, Extremities physiology, Lizards physiology
- Abstract
The remarkable ability of geckos to adhere to a wide-variety of surfaces has served as an inspiration for hundreds of studies spanning the disciplines of biomechanics, functional morphology, ecology, evolution, materials science, chemistry, and physics. The multifunctional properties (e.g., self-cleaning, controlled releasability, reversibility) and adhesive performance of the gekkotan adhesive system have motivated researchers to design and fabricate gecko-inspired synthetic adhesives of various materials and properties. However, many challenges remain in our attempts to replicate the properties and performance of this complex, hierarchical fibrillar adhesive system, stemming from fundamental, but unanswered, questions about how fibrillar adhesion operates. Such questions involve the role of fibril morphology in adhesive performance and how the gekkotan adhesive apparatus is utilized in nature. Similar fibrillar adhesive systems have, however, evolved independently in two other lineages of lizards (anoles and skinks) and potentially provide alternate avenues for addressing these fundamental questions. Anoles are the most promising group because they have been the subject of intensive ecological and evolutionary study for several decades, are highly speciose, and indeed are advocated as squamate model organisms. Surprisingly, however, comparatively little is known about the morphology, performance, and properties of their convergently-evolved adhesive arrays. Although many researchers consider the performance of the adhesive system of Anolis lizards to be less accomplished than its gekkotan counterpart, we argue here that Anolis lizards are prime candidates for exploring the fundamentals of fibrillar adhesion. Studying the less complex morphology of the anoline adhesive system has the potential to enhance our understanding of fibril morphology and its relationship to the multifunctional performance of fibrillar adhesive systems. Furthermore, the abundance of existing data on the ecology and evolution of anoles provides an excellent framework for testing hypotheses about the influence of habitat microstructure on the performance, behavior, and evolution of lizards with subdigital adhesive pads., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.) more...
- Published
- 2019
- Full Text
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46. The Ecomechanics of Gecko Adhesion: Natural Surface Topography, Evolution, and Biomimetics.
- Author
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Higham TE, Russell AP, Niewiarowski PH, Wright A, and Speck T
- Subjects
- Adhesiveness, Animals, Biomechanical Phenomena, Lizards anatomy & histology, Surface Properties, Biological Evolution, Biomimetic Materials analysis, Lizards physiology, Locomotion
- Abstract
The study of gecko adhesion is necessarily interdisciplinary due to the hierarchical nature of the adhesive system and the complexity of interactions between the animals and their habitats. In nature, geckos move on a wide range of surfaces including soft sand dunes, trees, and rocks, but much of the research over the past two decades has focused on their adhesive performance on artificial surfaces. Exploring the complex interactions between geckos and their natural habitats will reveal aspects of the adhesive system that can be applied to biomimetic research, such as the factors that facilitate movement on dirty and rough surfaces with varying microtopography. Additionally, contrasting suites of constraints and topographies are found on rocks and plants, likely driving differences in locomotion and morphology. Our overarching goals are to bring to light several aspects of ecology that are important for gecko-habitat interactions, and to propose a framework for how they can inspire material scientists and functional ecologists. We also present new data on surface roughness and topography of a variety of surfaces, and adhesive performance of Phelsuma geckos on surfaces of varying roughness. We address the following key questions: (1) why and how should ecology be incorporated into the study of gecko adhesion? (2) What topographical features of rocks and plants likely drive adhesive performance? (3) How can ecological studies inform material science research? Recent advances in surface replication techniques that eliminate confounding factors among surface types facilitate the ability to address some of these questions. We pinpoint gaps in our understanding and identify key initiatives that should be adopted as we move forward. Most importantly, fine details of locomotor microhabitat use of both diurnal and nocturnal geckos are needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.) more...
- Published
- 2019
- Full Text
- View/download PDF
47. MicroRNA suppression of stress-responsive NDRG2 during dexamethasone treatment in skeletal muscle cells.
- Author
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Mir BA, Islam R, Kalanon M, Russell AP, and Foletta VC
- Subjects
- 3' Untranslated Regions genetics, Animals, Binding Sites, Cell Line, Computer Simulation, Dexamethasone pharmacology, Gene Expression, Gene Expression Regulation, HEK293 Cells, Humans, Mice, Muscle Fibers, Skeletal drug effects, Protein Biosynthesis, Stress, Physiological drug effects, Transfection, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, MicroRNAs metabolism, Muscle Fibers, Skeletal metabolism, Stress, Physiological genetics
- Abstract
Background: MicroRNAs (miRNAs) are increasingly being identified as modulatory molecules for physiological and pathological processes in muscle. Here, we investigated whether miRNAs influenced the expression of the stress-responsive gene N-myc downstream-regulated gene 2 (Ndrg2) in skeletal muscle cells through the targeted degradation or translation inhibition of NDRG2 mRNA transcripts during basal or catabolic stress conditions., Results: Three miRNAs, mmu-miR-23a-3p (miR-23a), mmu-miR-23b-3p (miR-23b) and mmu-miR-28-5p (miR-28), were identified using an in silico approach and confirmed to target the 3' untranslated region of the mouse Ndrg2 gene through luciferase reporter assays. However, miR-23a, -23b or -28 overexpression had no influence on NDRG2 mRNA or protein levels up to 48 h post treatment in mouse C2C12 myotubes under basal conditions. Interestingly, a compensatory decrease in the endogenous levels of the miRNAs in response to each other's overexpression was measured. Furthermore, dexamethasone, a catabolic stress agent that induces NDRG2 expression, decreased miR-23a and miR-23b endogenous levels at 24 h post treatment suggesting an interplay between these miRNAs and NDRG2 regulation under similar stress conditions. Accordingly, when overexpressed simultaneously, miR-23a, -23b and -28 attenuated the dexamethasone-induced increase of NDRG2 protein translation but did not affect Ndrg2 gene expression., Conclusion: These findings highlight modulatory and co-regulatory roles for miR-23a, -23b and -28 and their novel regulation of NDRG2 during stress conditions in muscle. more...
- Published
- 2019
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48. Perm1 regulates CaMKII activation and shapes skeletal muscle responses to endurance exercise training.
- Author
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Cho Y, Tachibana S, Hazen BC, Moresco JJ, Yates JR 3rd, Kok B, Saez E, Ross RS, Russell AP, and Kralli A
- Subjects
- Adolescent, Adult, Animals, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Cell Line, Tumor, Child, Child, Preschool, Exercise Test, Female, Gene Knockdown Techniques, HEK293 Cells, Humans, Infant, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Muscle Proteins genetics, Muscular Dystrophies metabolism, Muscular Dystrophies pathology, Transfection, Young Adult, Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism, Endurance Training, Muscle Proteins metabolism, Muscle, Skeletal metabolism, Physical Conditioning, Animal
- Abstract
Objective: Endurance exercise training remodels skeletal muscle, leading to increased mitochondrial content and oxidative capacity. How exercise entrains skeletal muscle signaling pathways to induce adaptive responses remains unclear. In past studies, we identified Perm1 (PGC-1 and ERR induced regulator, muscle 1) as an exercise-induced gene and showed that Perm1 overexpression elicits similar muscle adaptations as endurance exercise training. The mechanism of action and the role of Perm1 in exercise-induced responses are not known. In this study, we aimed to determine the pathway by which Perm1 acts as well as the importance of Perm1 for acute and long-term responses to exercise., Methods: We performed immunoprecipitation and mass spectrometry to identify Perm1 associated proteins, and validated Perm1 interactions with the Ca
2+ /calmodulin-dependent protein kinase II (CaMKII). We also knocked down Perm1 expression in gastrocnemius muscles of mice via AAV-mediated delivery of shRNA and assessed the impact of reduced Perm1 expression on both acute molecular responses to a single treadmill exercise bout and long-term adaptive responses to four weeks of voluntary wheel running training. Finally, we asked whether Perm1 levels are modulated by diet or diseases affecting skeletal muscle function., Results: We show that Perm1 associates with skeletal muscle CaMKII and promotes CaMKII activation. In response to an acute exercise bout, muscles with a knock down of Perm1 showed defects in the activation of CaMKII and p38 MAPK and blunted induction of regulators of oxidative metabolism. Following four weeks of voluntary training, Perm1 knockdown muscles had attenuated mitochondrial biogenesis. Finally, we found that Perm1 expression is reduced in diet-induced obese mice and in muscular dystrophy patients and mouse models., Conclusions: Our findings identify Perm1 as a muscle-specific regulator of exercise-induced signaling and Perm1 levels as tuners of the skeletal muscle response to exercise. The decreased Perm1 levels in states of obesity or muscle disease suggest that Perm1 may link pathological states to inefficient exercise responses., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.) more...- Published
- 2019
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49. Lower rotational inertia and larger leg muscles indicate more rapid turns in tyrannosaurids than in other large theropods.
- Author
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Snively E, O'Brien H, Henderson DM, Mallison H, Surring LA, Burns ME, Holtz TR Jr, Russell AP, Witmer LM, Currie PJ, Hartman SA, and Cotton JR
- Abstract
Synopsis: Tyrannosaurid dinosaurs had large preserved leg muscle attachments and low rotational inertia relative to their body mass, indicating that they could turn more quickly than other large theropods., Methods: To compare turning capability in theropods, we regressed agility estimates against body mass, incorporating superellipse-based modeled mass, centers of mass, and rotational inertia (mass moment of inertia). Muscle force relative to body mass is a direct correlate of agility in humans, and torque gives potential angular acceleration. Agility scores therefore include rotational inertia values divided by proxies for (1) muscle force (ilium area and estimates of m. caudofemoralis longus cross-section), and (2) musculoskeletal torque. Phylogenetic ANCOVA (phylANCOVA) allow assessment of differences in agility between tyrannosaurids and non-tyrannosaurid theropods (accounting for both ontogeny and phylogeny). We applied conditional error probabilities a ( p ) to stringently test the null hypothesis of equal agility., Results: Tyrannosaurids consistently have agility index magnitudes twice those of allosauroids and some other theropods of equivalent mass, turning the body with both legs planted or pivoting over a stance leg. PhylANCOVA demonstrates definitively greater agilities in tyrannosaurids, and phylogeny explains nearly all covariance. Mass property results are consistent with those of other studies based on skeletal mounts, and between different figure-based methods (our main mathematical slicing procedures, lofted 3D computer models, and simplified graphical double integration)., Implications: The capacity for relatively rapid turns in tyrannosaurids is ecologically intriguing in light of their monopolization of large (>400 kg), toothed dinosaurian predator niches in their habitats., Competing Interests: The authors declare that they have no competing interests. more...
- Published
- 2019
- Full Text
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50. PGC-1α and PGC-1β Increase Protein Synthesis via ERRα in C2C12 Myotubes.
- Author
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Brown EL, Foletta VC, Wright CR, Sepulveda PV, Konstantopoulos N, Sanigorski A, Della Gatta P, Cameron-Smith D, Kralli A, and Russell AP
- Abstract
The transcriptional coactivators peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PGC-1β are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1α or PGC-1β overexpression in C2C12 myotubes increased protein synthesis and myotube diameter under basal conditions and attenuated the loss in protein synthesis following the treatment with the catabolic agent, dexamethasone. To investigate whether PGC-1α or PGC-1β signal through the Akt/mTOR pathway to increase protein synthesis, treatment with the PI3K and mTOR inhibitors, LY294002 and rapamycin, respectively, was undertaken but found unable to block PGC-1α or PGC-1β's promotion of protein synthesis. Furthermore, PGC-1α and PGC-1β decreased phosphorylation of Akt and the Akt/mTOR substrate, p70S6K. In contrast to Akt/mTOR inhibition, the suppression of ERRα, a major effector of PGC-1α and PGC-1β activity, attenuated the increase in protein synthesis and myotube diameter in the presence of PGC-1α or PGC-1β overexpression. To characterize further the biological processes occurring, gene set enrichment analysis of genes commonly regulated by both PGC-1α and PGC-1β was performed following a microarray screen. Genes were found enriched in metabolic and mitochondrial oxidative processes, in addition to protein translation and muscle development categories. This suggests concurrent responses involving both increased metabolism and myotube protein synthesis. Finally, based on their known function or unbiased identification through statistical selection, two sets of genes were investigated in a human exercise model of stimulated protein synthesis to characterize further the genes influenced by PGC-1α and PGC-1β during physiological adaptive changes in skeletal muscle. more...
- Published
- 2018
- Full Text
- View/download PDF
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