162 results on '"Changhan Lee"'
Search Results
2. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
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Byung Soo Kong, Changhan Lee, and Young Min Cho
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aging ,diabetes mellitus, type 2 ,intracellular signaling peptides and proteins ,mitochondria ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.
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- 2023
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3. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
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Joseph C. Reynolds, Rochelle W. Lai, Jonathan S. T. Woodhead, James H. Joly, Cameron J. Mitchell, David Cameron-Smith, Ryan Lu, Pinchas Cohen, Nicholas A. Graham, Bérénice A. Benayoun, Troy L. Merry, and Changhan Lee
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Science - Abstract
Exercise has beneficial effects on metabolism and overall physiologic fitness in aged organisms. Here the authors show that MOTS-c is a mitochondrial-encoded exercise-induced peptide that regulates skeletal muscle metabolism and improves healthspan of older mice.
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- 2021
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4. Optimization of Transposon Mutagenesis Methods in Pseudomonas antarctica
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Sangha Kim and Changhan Lee
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Pseudomonas ,Pseudomonas antarctica ,transposon ,transposon insertion mutant library ,Biology (General) ,QH301-705.5 - Abstract
Pseudomonas is a widespread genus in various host and environmental niches. Pseudomonas exists even in extremely cold environments such as Antarctica. Pseudomonas antarctica is a psychrophilic bacterium isolated from Antarctica. P. antarctica is also known to produce antimicrobial substances. Although P. antarctica can provide insight into how bacteria have adapted to low temperatures and has significant potential for developing novel antimicrobial substances, progress in genetic and molecular studies has not been achieved. Transposon mutagenesis is a useful tool to screen genes of interest in bacteria. Therefore, we attempted for the first time in P. antarctica to generate transposon insertion mutants using the transfer of a conjugational plasmid encoding a transposon. To increase the yield of transposon insertion mutants, we optimized the methods, in terms of temperature for conjugation, the ratio of donor and recipient during conjugation, and the concentration of antibiotics. Here, we describe the optimized methods to successfully generate transposon insertion mutants in P. antarctica.
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- 2023
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5. Protocol for the assessment of human T cell activation by real-time metabolic flux analysis
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Byung Soo Kong, Changhan Lee, and Young Min Cho
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Classification Description: Cell Biology ,Cell isolation ,Cell-based Assays ,Immunology ,Metabolism ,Science (General) ,Q1-390 - Abstract
Summary: The elevation of glycolysis in autoreactive T cells is a key target for the prevention and treatment of T cell-related autoimmune diseases, such as type 1 diabetes (T1D). Here, we describe a simple and efficient protocol for isolating human peripheral blood mononuclear cells (PBMCs) and T cells, and the subsequent assessment of T cell glycolysis using Seahorse analyzer. This protocol is useful to analyze different subsets of T cells and applicable to different autoimmune disease models (i.e., T1D, multiple sclerosis).For complete details on the use and execution of this profile, please refer to Kong et al. (2021).
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- 2022
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6. Remodeling of the H3 nucleosomal landscape during mouse aging
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Yilin Chen, Juan I. Bravo, Jyung Mean Son, Changhan Lee, and Bérénice A. Benayoun
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Aging ,Nucleosome ,Epigenome ,H3 ,Medicine - Abstract
In multi-cellular organisms, the control of gene expression is key not only for development, but also for adult cellular homeostasis, and deregulation of gene expression correlates with aging. A key layer in the study of gene regulation mechanisms lies at the level of chromatin: cellular chromatin states (i.e. the ‘epigenome’) can tune transcriptional profiles, and, in line with the prevalence of transcriptional alterations with aging, accumulating evidence suggests that the chromatin landscape is altered with aging across cell types and species. However, although alterations in the chromatin make-up of cells are considered to be a hallmark of aging, little is known of the genomic loci that are specifically affected by age-related chromatin state remodeling and of their biological significance. Here, we report the analysis of genome-wide profiles of core histone H3 occupancy in aging male mouse tissues (i.e. heart, liver, cerebellum and olfactory bulb) and primary cultures of neural stem cells. We find that, although no drastic changes in H3 levels are observed, local changes in H3 occupancy occur with aging across tissues and cells with both regions of increased or decreased occupancy. These changes are compatible with a general increase in chromatin accessibility at pro-inflammatory genes and may thus mechanistically underlie known shift in gene expression programs during aging.
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- 2020
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7. Protein folding while chaperone bound is dependent on weak interactions
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Kevin Wu, Frederick Stull, Changhan Lee, and James C. A. Bardwell
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Science - Abstract
Spy is an ATP independent chaperone that allows folding of its client protein Im7 while continuously bound to Spy. Here the authors employ kinetics measurements to study the folding of another Spy client protein SH3 and find that Spy’s ability to allow a client to fold while bound is inversely related to how strongly it interacts with that client.
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- 2019
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8. Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
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Byung Soo Kong, Se Hee Min, Changhan Lee, and Young Min Cho
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Biology (General) ,QH301-705.5 - Published
- 2021
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9. Stress-Responsive Periplasmic Chaperones in Bacteria
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Hyunhee Kim, Kevin Wu, and Changhan Lee
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periplasmic chaperone ,Spy ,DegP ,HdeA ,HdeB ,UgpB ,Biology (General) ,QH301-705.5 - Abstract
Periplasmic proteins are involved in a wide range of bacterial functions, including motility, biofilm formation, sensing environmental cues, and small-molecule transport. In addition, a wide range of outer membrane proteins and proteins that are secreted into the media must travel through the periplasm to reach their final destinations. Since the porous outer membrane allows for the free diffusion of small molecules, periplasmic proteins and those that travel through this compartment are more vulnerable to external environmental changes, including those that result in protein unfolding, than cytoplasmic proteins are. To enable bacterial survival under various stress conditions, a robust protein quality control system is required in the periplasm. In this review, we focus on several periplasmic chaperones that are stress responsive, including Spy, which responds to envelope-stress, DegP, which responds to temperature to modulate chaperone/protease activity, HdeA and HdeB, which respond to acid stress, and UgpB, which functions as a bile-responsive chaperone.
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- 2021
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10. Investigation on the Printed CNT-Film-Based Electrochemical Sensor for Detection of Liquid Chemicals
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Jaeha Noh, Sangsu An, Changhan Lee, Jiho Chang, Snagtae Lee, Moonjin Lee, and Dongmin Seo
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carbon nanotubes (CNT) ,printed CNT film (PCF) ,electrochemical sensor ,hazardous ,noxious substances (HNS) ,Chemical technology ,TP1-1185 - Abstract
We studied electrochemical sensors using printed carbon nanotubes (CNT) film on a polyethylene telephtalate (PET) substrate. The mechanical stability of the printed CNT film (PCF) was confirmed by using bending and Scotch tape tests. In order to determine the optimum sensor structure, a resistance-type PCF sensor (R-type PCF sensor) and a comb-type PCF sensor (C-type PCF sensor) were fabricated and compared using a diluted NH3 droplet with various concentrations. The magnitude of response, response time, sensitivity, linearity, and limit of detection (LOD) were compared, and it was concluded that C-type PCF sensor has superior performance. In addition, the feasibility of PCF electrochemical sensor was investigated using 12 kinds of hazardous and noxious substances (HNS). The detection mechanism and selectivity of the PCF sensor are discussed.
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- 2021
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11. Two FtsH Proteases Contribute to Fitness and Adaptation of Pseudomonas aeruginosa Clone C Strains
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Shady Mansour Kamal, Morten Levin Rybtke, Manfred Nimtz, Stefanie Sperlein, Christian Giske, Janja Trček, Julien Deschamps, Romain Briandet, Luciana Dini, Lothar Jänsch, Tim Tolker-Nielsen, Changhan Lee, and Ute Römling
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Pseudomonas aeruginosa ,clone C strains ,FtsH protease ,heat shock factor RpoH ,phenazine ,secondary metabolite ,Microbiology ,QR1-502 - Abstract
Pseudomonas aeruginosa is an environmental bacterium and a nosocomial pathogen with clone C one of the most prevalent clonal groups. The P. aeruginosa clone C specific genomic island PACGI-1 harbors a xenolog of ftsH encoding a functionally diverse membrane-spanning ATP-dependent metalloprotease on the core genome. In the aquatic isolate P. aeruginosa SG17M, the core genome copy ftsH1 significantly affects growth and dominantly mediates a broad range of phenotypes, such as secretion of secondary metabolites, swimming and twitching motility and resistance to aminoglycosides, while the PACGI-1 xenolog ftsH2 backs up the phenotypes in the ftsH1 mutant background. The two proteins, with conserved motifs for disaggregase and protease activity present in FtsH1 and FtsH2, have the ability to form homo- and hetero-oligomers with ftsH2 distinctively expressed in the late stationary phase of growth. However, mainly FtsH1 degrades a major substrate, the heat shock transcription factor RpoH. Pull-down experiments with substrate trap-variants inactive in proteolytic activity indicate both FtsH1 and FtsH2 to interact with the inhibitory protein HflC, while the phenazine biosynthesis protein PhzC was identified as a substrate of FtsH1. In summary, as an exception in P. aeruginosa, clone C harbors two copies of the ftsH metallo-protease, which cumulatively are required for the expression of a diversity of phenotypes.
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- 2019
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12. Nuclear transcriptional regulation by mitochondrial-encoded MOTS-c
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Changhan Lee
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mitochondria ,mitonuclear communication ,mitochondrial-derived peptides ,mdps ,mots-c ,nuclear translocation ,adaptive gene expression ,stress response ,stress resistance ,homeostasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cellular stress response is coordinated through the communication between mitochondria and the nucleus. However, whereas mitochondria are regulated by nuclear-encoded proteins, the nucleus was considered ungoverned by mitochondrial-encoded factors. We recently reported that a mitochondrial-encoded peptide directly regulates the nuclear genome upon cellular stress, indicating an integrated bi-genomic cross-communication mechanism.
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- 2019
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13. Correction: Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
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Stefano Di Biase, Hong Seok Shim, Kyung Hwa Kim, Manlio Vinciguerra, Francesca Rappa, Min Wei, Sebastian Brandhorst, Francesco Cappello, Hamed Mirzaei, Changhan Lee, and Valter D Longo
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Biology (General) ,QH301-705.5 - Abstract
[This corrects the article DOI: 10.1371/journal.pbio.2001951.].
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- 2017
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14. Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
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Stefano Di Biase, Hong Seok Shim, Kyung Hwa Kim, Manlio Vinciguerra, Francesca Rappa, Min Wei, Sebastian Brandhorst, Francesco Cappello, Hamed Mirzaei, Changhan Lee, and Valter D Longo
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Biology (General) ,QH301-705.5 - Abstract
Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (PKA) to accelerate aging by inhibiting transcription factors Msn2/4. Here, we show that fasting or glucose restriction (GR) regulate PKA and AMP-activated protein kinase (AMPK) to protect against DXR in part by activating the mammalian Msn2/4 ortholog early growth response protein 1 (EGR1). Increased expression of the EGR1-regulated cardioprotective peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart tissue may also contribute to DXR resistance. Our findings suggest the existence of a glucose-PKA pathway that inactivates conserved zinc finger stress-resistance transcription factors to sensitize cells to toxins conserved from yeast to mammals. Our findings also describe a toxic role for drugs widely used in cancer treatment that promote hyperglycemia and identify dietary interventions that reverse these effects.
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- 2017
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15. Dietary restriction with and without caloric restriction for healthy aging [version 1; referees: 3 approved]
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Changhan Lee and Valter Longo
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Aging ,Animal Genetics ,Control of Gene Expression ,Developmental Molecular Mechanisms ,Endocrinology ,Integrative Physiology ,Medical Genetics ,Neurobiology of Disease & Regeneration ,Medicine ,Science - Abstract
Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction.
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- 2016
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16. Bacterial Responses to Glyoxal and Methylglyoxal: Reactive Electrophilic Species
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Changhan Lee and Chankyu Park
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glyoxal ,reactive electrophilic species (RES) ,glyoxalase ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Glyoxal (GO) and methylglyoxal (MG), belonging to α-oxoaldehydes, are produced by organisms from bacteria to humans by glucose oxidation, lipid peroxidation, and DNA oxidation. Since glyoxals contain two adjacent reactive carbonyl groups, they are referred to as reactive electrophilic species (RES), and are damaging to proteins and nucleotides. Therefore, glyoxals cause various diseases in humans, such as diabetes and neurodegenerative diseases, from which all living organisms need to be protected. Although the glyoxalase system has been known for some time, details on how glyoxals are sensed and detoxified in the cell have not been fully elucidated, and are only beginning to be uncovered. In this review, we will summarize the current knowledge on bacterial responses to glyoxal, and specifically focus on the glyoxal-associated regulators YqhC and NemR, as well as their detoxification mediated by glutathione (GSH)-dependent/independent glyoxalases and NAD(P)H-dependent reductases. Furthermore, we will address questions and future directions.
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- 2017
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17. Fasting enhances the response of glioma to chemo- and radiotherapy.
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Fernando Safdie, Sebastian Brandhorst, Min Wei, Weijun Wang, Changhan Lee, Saewon Hwang, Peter S Conti, Thomas C Chen, and Valter D Longo
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Medicine ,Science - Abstract
Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.To test the effect of starvation on glioma cells in vitro, we treated primary mouse glia, murine GL26, rat C6 and human U251, LN229 and A172 glioma cells with Temozolomide in ad lib and STS mimicking conditions. In vivo, mice with subcutaneous or intracranial models of GL26 glioma were starved for 48 hours prior to radio- or chemotherapy and the effects on tumor progression and survival were measured. Starvation-mimicking conditions sensitized murine, rat and human glioma cells, but not primary mixed glia, to chemotherapy. In vivo, starvation for 48 hours, which causes a significant reduction in blood glucose and circulating insulin-like growth factor 1 (IGF-1) levels, sensitized both subcutaneous and intracranial glioma models to radio-and chemotherapy.Starvation-induced cancer sensitization to radio- or chemotherapy leads to extended survival in the in vivo glioma models tested. These results indicate that fasting and fasting-mimicking interventions could enhance the efficacy of existing cancer treatments against aggressive glioma in patients.
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- 2012
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18. Performance Improvement of Indium Tin Oxide Electrochemical Sensor by Mixing Carbon Black.
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Changhan Lee, Sangsu An, Youngji Cho, Jiho Chang, Jaejin Park, and Moonjin Lee
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INDIUM tin oxide ,ELECTROCHEMICAL sensors ,CARBON-black ,SURFACE resistance ,OXIDE coating ,CUCURBITURIL ,MANUFACTURING processes ,METALLIC oxides - Abstract
We studied a method of implementing an electrochemical sensor with high response speed using a film made of metal oxide nanoparticles. The optimal conditions for sensor production were estimated by calculating the sensor's response when the bulk and surface resistances of the film changed. We also implemented a new manufacturing process to fabricate the sensor. To achieve high response speed, an ITO:CB film was produced by mixing ITO nanoparticles and carbon black (CB) powder. Depending on the CB content of the ITO:CB film, the response time of the sensor continued to decrease from 337 s (CB = 0 wt%) to 2 s (CB = 50 wt%). However, even in this case, a continuous decrease in response intensity was observed as well. Therefore, to ensure high response speed and appropriate response intensity, a new process of oxygen ashing the film surface was introduced. As a result, it was possible to secure high response intensity and high response speed at CB contents up to 30 wt%. On the basis of these results, we confirmed that CB mixing and surface oxygen ashing can improve both the response intensity and speed of sensors using metal oxide nanoparticle films. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
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Young Min Cho, Changhan Lee, and ByungSoo Kong
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Endocrinology, Diabetes and Metabolism - Abstract
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.
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- 2023
20. Temperature Matters: Bacterial Response to Temperature Change
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Seongjoon Moon, Soojeong Ham, Juwon Jeong, Heechan Ku, Hyunhee Kim, and Changhan Lee
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General Medicine ,Applied Microbiology and Biotechnology ,Microbiology - Published
- 2023
21. Temperature-Dependent Characteristics of Carbon Nanotubes-Film-Based Electrochemical Sensor
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Jaeha Noh, Hyung Soo Ahn, Sangsu An, Changhan Lee, Sangtae Lee, Moonjin Lee, Dongmin Seo, and Jiho Chang
- Published
- 2022
22. ATP-Independent Chaperones
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Rishav Mitra, Kevin Wu, Changhan Lee, and James C.A. Bardwell
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Protein Folding ,Adenosine Triphosphate ,Protein Conformation ,Structural Biology ,Biophysics ,Humans ,Bioengineering ,Cell Biology ,Biochemistry ,Molecular Chaperones - Abstract
The folding of proteins into their native structure is crucial for the functioning of all biological processes. Molecular chaperones are guardians of the proteome that assist in protein folding and prevent the accumulation of aberrant protein conformations that can lead to proteotoxicity. ATP-independent chaperones do not require ATP to regulate their functional cycle. Although these chaperones have been traditionally regarded as passive holdases that merely prevent aggregation, recent work has shown that they can directly affect the folding energy landscape by tuning their affinity to various folding states of the client. This review focuses on emerging paradigms in the mechanism of action of ATP-independent chaperones and on the various modes of regulating client binding and release.
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- 2022
23. Supplementary Methods, Figures 1-8 from Reduced Levels of IGF-I Mediate Differential Protection of Normal and Cancer Cells in Response to Fasting and Improve Chemotherapeutic Index
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Valter D. Longo, Giovanna Bianchi, Pinchas Cohen, David Hwang, Edoardo Parrella, Federica Madia, Min Wei, Lizzia Raffaghello, Fernando M. Safdie, and Changhan Lee
- Abstract
Supplementary Methods, Figures 1-8 from Reduced Levels of IGF-I Mediate Differential Protection of Normal and Cancer Cells in Response to Fasting and Improve Chemotherapeutic Index
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- 2023
24. Data from Reduced Levels of IGF-I Mediate Differential Protection of Normal and Cancer Cells in Response to Fasting and Improve Chemotherapeutic Index
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Valter D. Longo, Giovanna Bianchi, Pinchas Cohen, David Hwang, Edoardo Parrella, Federica Madia, Min Wei, Lizzia Raffaghello, Fernando M. Safdie, and Changhan Lee
- Abstract
Inhibitors of the insulin-like growth factor-I (IGF-I) receptor have been widely studied for their ability to enhance the killing of a variety of malignant cells, but whether IGF-I signaling differentially protects the host and cancer cells against chemotherapy is unknown. Starvation can protect mice, but not cancer cells, against high-dose chemotherapy [differential stress resistance (DSR)]. Here, we offer evidence that IGF-I reduction mediates part of the starvation-dependent DSR. A 72-hour fast in mice reduced circulating IGF-I by 70% and increased the level of the IGF-I inhibitor IGFBP-1 by 11-fold. LID mice, with a 70% to 80% reduction in circulating IGF-I levels, were protected against three of four chemotherapy drugs tested. Restoration of IGF-I was sufficient to reverse the protective effect of fasting. Sixty percent of melanoma-bearing LID mice treated with doxorubicin achieved long-term survival whereas all control mice died of either metastases or chemotherapy toxicity. Reducing IGF-I/IGF-I signaling protected primary glia, but not glioma cells, against cyclophosphamide and protected mouse embryonic fibroblasts against doxorubicin. Further, S. cerevisiae lacking homologs of IGF-I signaling proteins were protected against chemotherapy-dependent DNA damage in a manner that could be reversed by expressing a constitutively active form of Ras. We conclude that normal cells and mice can be protected against chemotherapy-dependent damage by reducing circulating IGF-I levels and by a mechanism that involves downregulation of proto-oncogene signals. Cancer Res; 70(4); 1564–72
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- 2023
25. Study on the Effect of the Electrode Structure of an ITO Nanoparticle Film Sensor On Operating Performance
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Sangsu An, Jaeha Noh, Changhan Lee, Sangtae Lee, Dongmin Seo, Moonjin Lee, and Jiho Chang
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- 2022
26. pH Sensor Application of Printed Indium-Tin-Oxide Nanoparticle Films
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Changhan Lee, Jaeha Noh, Sangsu An, Sangtae Lee, Dongmin Seo, Moonjin Lee, and Jiho Chang
- Published
- 2022
27. ITO Nanoparticle Chemiresistive Sensor for Detecting Liquid Chemicals Diluted in Brine
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Sangsu An, Dongwan Ko, Jaeha Noh, Changhan Lee, Dongmin Seo, Moonjin Lee, and Jiho Chang
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Electrical and Electronic Engineering ,Electronic, Optical and Magnetic Materials - Published
- 2022
28. A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
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Hyunhee, Kim, Juwon, Jeong, and Changhan, Lee
- Abstract
Parkinson's disease is the second most common neurodegenerative disorder and is characterized by progressive cell death caused by the formation of Lewy bodies containing misfolded and aggregated α-synuclein. α-synuclein is an abundant presynaptic protein that regulates synaptic vesicle trafficking, but the accumulation of its proteinaceous inclusions results in neurotoxicity. Recent studies have revealed that various genetic factors, including bacterial chaperones, could reduce the formation of α-synuclein aggregates in vitro. However, it is also important to monitor the anti-aggregation effect in the cell to apply this as a potential treatment for the patients. It would be ideal to use neuronal cells, but these cells are difficult to handle and take a long time to exhibit the anti-aggregation phenotype. Therefore, a quick and effective in vivo tool is required for the further evaluation of in vivo anti-aggregation activity. The method described here was used to monitor and analyze the anti-aggregation phenotype in the humanized yeast Saccharomyces cerevisiae, which expressed human α-synuclein. This protocol demonstrates in vivo tools that could be used for monitoring α-synuclein-induced cellular toxicity, as well as the formation of α-synuclein aggregates in cells.
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- 2022
29. A Method to Study α-Synuclein Toxicity and Aggregation Using a Humanized Yeast Model
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Changhan Lee, Juwon Jeong, and Hyunhee Kim
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General Immunology and Microbiology ,General Chemical Engineering ,General Neuroscience ,General Biochemistry, Genetics and Molecular Biology - Published
- 2022
30. Study on the International Standardization for the Semantic Metadata Mapping Procedure.
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Sungjoon Lim, Taesul Seo, Changhan Lee, and Soungsoo Shin
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- 2012
- Full Text
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31. Aging: All roads lead to mitochondria
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Jyung Mean Son and Changhan Lee
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0301 basic medicine ,Genome instability ,Aging ,Mitochondrial DNA ,Bioenergetics ,Context (language use) ,Cell Biology ,Mitochondrion ,Biology ,Genome ,Article ,Mitochondria ,Rats ,Mice ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Animals ,Humans ,Neuroscience ,030217 neurology & neurosurgery ,Function (biology) ,Developmental Biology ,Free-radical theory of aging - Abstract
Mitochondria were described as early as 1890 as ubiquitous intracellular structures by Ernster and Schatz (1981) [1]. Since then, the accretion of knowledge in the past century has revealed much of the molecular details of mitochondria, ranging from mitochondrial origin, structure, metabolism, genetics, and signaling, and their implications in health and disease. We now know that mitochondria are remarkably multifunctional and deeply intertwined with many vital cellular processes. They are quasi-self organelles that still possess remnants of its bacterial ancestry, including an independent genome. The mitochondrial free radical theory of aging (MFRTA), which postulated that aging is a product of oxidative damage to mitochondrial DNA, provided a conceptual framework that put mitochondria on the map of aging research. However, several studies have more recently challenged the general validity of the theory, favoring novel ideas based on emerging evidence to understand how mitochondria contribute to aging and age-related diseases. One prominent topic of investigation lies on the fact that mitochondria are not only production sites for bioenergetics and macromolecules, but also regulatory hubs that communicate and coordinate many vital physiological processes at the cellular and organismal level. The bi-directional communication and coordination between the co-evolved mitochondrial and nuclear genomes is especially interesting in terms of cellular regulation. Mitochondria are dynamic and adaptive, rendering their function sensitive to cellular context. Tissues with high energy demands, such as the brain, seem to be uniquely affected by age-dependent mitochondrial dysfunction, providing a foundation for the development of novel mitochondrial-based therapeutics and diagnostics.
- Published
- 2021
32. Liquid electrochemical sensors using carbon nanotube film
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Sangsu An, Changhan Lee, Moonjin Lee, Jiho Chang, Jaeha Noh, Sangtae Lee, and Dongmin Seo
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Materials science ,Chemical engineering ,law ,Carbon nanotube ,Electrochemistry ,law.invention - Published
- 2021
33. Profiling of RNA-binding Proteins Interacting With Glucagon and Adipokinetic Hormone mRNAs
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Seungbeom Ko, Eunbyul Yeom, Yoo Lim Chun, Hyejin Mun, Marina Howard-McGuire, Nathan T. Millison, Junyang Jung, Kwang-Pyo Lee, Changhan Lee, Kyu-Sun Lee, Joe R. Delaney, and Je-Hyun Yoon
- Subjects
Mass spectrometry ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Original Article ,RNA-binding proteins ,Cardiology and Cardiovascular Medicine ,Glucagon - Abstract
Objective Glucagon in mammals and its homolog (adipokinetic hormone [AKH] in Drosophila melanogaster) are peptide hormones which regulate lipid metabolism by breaking down triglycerides. Although regulatory mechanisms of glucagon and AKH expression have been widely studied, post-transcriptional gene expression of glucagon has not been investigated thoroughly. In this study, we aimed to profile proteins binding with Gcg messenger RNA (mRNA) in mouse and Akh mRNA in Drosophila. Methods Drosophila Schneider 2 (S2) and mouse 3T3-L1 cell lysates were utilized for affinity pull down of Akh and Gcg mRNA respectively using biotinylated anti-sense DNA oligoes against target mRNAs. Mass spectrometry and computational network analysis revealed mRNA-interacting proteins residing in functional proximity. Results We observed that 1) 91 proteins interact with Akh mRNA from S2 cell lysates, 2) 34 proteins interact with Gcg mRNA from 3T3-L1 cell lysates. 3) Akh mRNA interactome revealed clusters of ribosomes and known RNA-binding proteins (RBPs). 4) Gcg mRNA interactome revealed mRNA-binding proteins including Plekha7, zinc finger protein, carboxylase, lipase, histone proteins and a cytochrome, Cyp2c44. 5) Levels of Gcg mRNA and its interacting proteins are elevated in skeletal muscles isolated from old mice compared to ones from young mice. Conclusion Akh mRNA in S2 cells are under active translation in a complex of RBPs and ribosomes. Gcg mRNA in mouse precursor adipocyte is in a condition distinct from Akh mRNA due to biochemical interactions with a subset of RBPs and histones. We anticipate that our study contributes to investigating regulatory mechanisms of Gcg and Akh mRNA decay, translation, and localization.
- Published
- 2021
34. Cytoplasmic molecular chaperones in Pseudomonas species
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Hyunhee Kim, Seongjoon Moon, Soojeong Ham, Kihyun Lee, Ute Römling, and Changhan Lee
- Subjects
Biodegradation, Environmental ,Pseudomonas aeruginosa ,Humans ,Pseudomonas syringae ,General Medicine ,Plants ,Applied Microbiology and Biotechnology ,Microbiology ,Molecular Chaperones - Abstract
Pseudomonas is widespread in various environmental and host niches. To promote rejuvenation, cellular protein homeostasis must be finely tuned in response to diverse stresses, such as extremely high and low temperatures, oxidative stress, and desiccation, which can result in protein homeostasis imbalance. Molecular chaperones function as key components that aid protein folding and prevent protein denaturation. Pseudomonas, an ecologically important bacterial genus, includes human and plant pathogens as well as growth-promoting symbionts and species useful for bioremediation. In this review, we focus on protein quality control systems, particularly molecular chaperones, in ecologically diverse species of Pseudomonas, including the opportunistic human pathogen Pseudomonas aeruginosa, the plant pathogen Pseudomonas syringae, the soil species Pseudomonas putida, and the psychrophilic Pseudomonas antarctica.
- Published
- 2022
35. Enhanced delivery of low-dose of aducanumab via FUS in 5xFAD mice, an AD model
- Author
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Chanho Kong, Eun-Jeong Yang, Jaewoo Shin, Junwon Park, Si-Hyun Kim, Won Seok Chang, Changhan Lee, Hyunju Kim, Hye-Sun Kim, and Jin Woo Chang
- Abstract
BackgroundAducanumab (Adu), which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid (Aβ), has been reported to reduce amyloid pathology and improve impaired cognition after the administration of a high dose (10 mg/kg) of the drug in Alzheimer’s disease (AD) clinical trials. The purpose of this study is to investigate the effects of a lower dose of Adu (3mg/kg) with enhanced delivery via focused ultrasound (FUS) in an AD mouse model.MethodsThe FUS with microbubbles opened the blood-brain barrier of the hippocampus for the delivery of Aducanumab. Combined therapy of FUS and Aducanumab was performed three times in total and each treatment was performed biweekly. Y-maze test, Brdu labeling, immunohistochemical experimental methods were employed in this study. In addition, RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental animals.ResultsThe combined treatment with FUS markedly increased the delivery of Adu into the brain by approximately 8.1 times in the brains. The combined treatment significantly restored cognitive impairment and decreased the level of amyloid plaques in the hippocampi of 5xFAD mice compared with Adu or FUS alone. The combined treatment with FUS and Adu increased reactive microglia and astrocytes associated with amyloid plaques in the hippocampi of 5xFAD mice. Furthermore, RNA sequencing identified 4 enriched canonical pathways such as phagosome formation, neuroinflammation signaling, CREB signaling and reelin signaling was altered in the hippocami of 5xFAD given the combined treatment. ConclusionIn conclusion, the enhanced delivery of a low dose of Aducanumab via FUS decreased amyloid deposits and restored cognitive function. This study provides better insight into establishing a solid therapeutic strategy for the treatment of AD as well as other neurodegenerative diseases.
- Published
- 2022
36. MITOCHONDRIAL COMMUNICATION AND AGING
- Author
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Changhan Lee
- Subjects
Health (social science) ,Life-span and Life-course Studies ,Health Professions (miscellaneous) - Abstract
Mitochondria evidently originate from endosymbiotic bacteria that presumably provided several advantages for eukaryotic life. For the past 1–2 billion years, mitochondria co-evolved with the ancestral cell to coordinate various cellular functions. Coordination requires communication and mitochondrial signaling has been shown to be vital to cellular fitness and aging. In this symposium, the speakers will discuss the role of mitochondria as a signaling organelle and their impact on key cellular functions in the context of aging. Consistent with emerging evidence of the complexity and sophistication of mitochondrial communication mechanisms, some of the mitochondrial-to-nuclear communication modes, including nuclear transcriptional programs and cellular signaling networks, that regulate molecular and cellular processes to promote fitness will be discussed. Dr. Chen will discuss how a mitochondrial metabolic checkpoint can regulate stem cell quiescence and maintenance that is important to stem cell aging. Dr. Picard will discuss the impact of mitochondrial stress on increased energetic cost of living (i.e. hypermetabolism) and cellular lifespan. Finally, Dr. Lee will discuss how signaling peptides that are encoded withing the mitochondrial genome regulate cellular homeostasis, increase physiological resilience, and promote healthy aging.
- Published
- 2022
37. A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c
- Author
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Roberto Vicinanza, Kaname Kojima, Su-Jeong Kim, Keitaro Tanaka, Pinchas Cohen, Changhan Lee, Yasumichi Arai, Timothy M. Moore, Seiji Maeda, Yesha M. Pate, Yoichi Sutoh, Kengo Kinoshita, Yuichiro Nishida, Jialin Xiao, Brendan Miller, Hemal H. Mehta, Hisashi Naito, Noriyuki Fuku, Andrea L. Hevener, Nobuyoshi Hirose, Eri Miyamoto-Mikami, Megumi Hara, Veronica Wendy Setiawan, Hiroshi Kumagai, Kelvin Yen, Hirofumi Zempo, Junxiang Wan, Yasuki Higaki, and Atsushi Shimizu
- Subjects
Adult ,Male ,Aging ,medicine.medical_specialty ,Mitochondrial DNA ,Mitochondrial-Derived Peptide MOTS-c ,endocrine system diseases ,medicine.medical_treatment ,mitochondrial DNA ,Type 2 diabetes ,Biology ,DNA, Mitochondrial ,Polymorphism, Single Nucleotide ,polymorphism ,Mitochondrial Proteins ,Mice ,Insulin resistance ,Polymorphism (computer science) ,3T3-L1 Cells ,insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Insulin ,Genetic Predisposition to Disease ,Aged ,Aged, 80 and over ,diabetes ,Cell Biology ,Middle Aged ,medicine.disease ,In vitro ,Glucose ,Endocrinology ,Diabetes Mellitus, Type 2 ,Female ,Proto-Oncogene Proteins c-akt ,MOTS-c ,Research Paper - Abstract
Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.
- Published
- 2021
38. A Study on the Influence of Stress and Depression on Suicidal Ideation of Police Officers –Focusing on Social Support
- Author
-
HEUNGKI MIN and CHANGHAN LEE
- Subjects
Rehabilitation ,Physical Therapy, Sports Therapy and Rehabilitation ,General Medicine - Published
- 2020
39. Mitochondrial-derived peptides in energy metabolism
- Author
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Alex Chan, Changhan Lee, Joseph C. Reynolds, Jonathan S. T. Woodhead, Troy L. Merry, Hiroshi Kumagai, and Su-Jeong Kim
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Mitochondrial DNA ,Physiology ,Endocrinology, Diabetes and Metabolism ,Cell ,Biology ,Mitochondrion ,MT-RNR1 ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Gene ,Humanin ,Mini-Review ,Mitochondria ,Cell biology ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Retrograde signaling ,Energy Metabolism ,Peptides ,030217 neurology & neurosurgery - Abstract
Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metaboloprotective properties. The 12S ribosomal RNA ( MT-RNR1) gene harbors the sequence for MOTS-c, whereas the other seven MDPs [humanin and small humanin-like peptides (SHLP) 1–6] are encoded by the 16S ribosomal RNA gene. Here, we review the evidence that endogenous MDPs are sensitive to changes in metabolism, showing that metabolic conditions like obesity, diabetes, and aging are associated with lower circulating MDPs, whereas in humans muscle MDP expression is upregulated in response to stress that perturbs the mitochondria like exercise, some mtDNA mutation-associated diseases, and healthy aging, which potentially suggests a tissue-specific response aimed at restoring cellular or mitochondrial homeostasis. Consistent with this, treatment of rodents with humanin, MOTS-c, and SHLP2 can enhance insulin sensitivity and offer protection against a range of age-associated metabolic disorders. Furthermore, assessing how mtDNA variants alter the functions of MDPs is beginning to provide evidence that MDPs are metabolic signal transducers in humans. Taken together, MDPs appear to form an important aspect of a retrograde signaling network that communicates mitochondrial status with the wider cell and to distal tissues to modulate adaptative responses to metabolic stress. It remains to be fully determined whether the metaboloprotective properties of MDPs can be harnessed into therapies for metabolic disease.
- Published
- 2020
40. Why? – Successful Pseudomonas aeruginosa clones with a focus on clone C
- Author
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Janja Trček, Sebastian Fischer, Ute Römling, Burkhard Tümmler, Changhan Lee, and Jens Klockgether
- Subjects
Thermotolerance ,Genomic Islands ,Locus (genetics) ,Review Article ,pulsed field gel electrophoresis ,Biology ,medicine.disease_cause ,ENCODE ,Microbiology ,Genome ,genomic island ,Plasmid ,Genomic island ,medicine ,Gene ,FtsH ,protein homeostasis ,Whole genome sequencing ,Genetics ,AcademicSubjects/SCI01150 ,whole genome sequencing ,Pseudomonas aeruginosa ,disaggregase ,Genetic Variation ,Clone Cells ,Infectious Diseases ,Genome, Bacterial ,Plasmids - Abstract
The environmental species Pseudomonas aeruginosa thrives in a variety of habitats. Within the epidemic population structure of P. aeruginosa, occassionally highly successful clones that are equally capable to succeed in the environment and the human host arise. Framed by a highly conserved core genome, individual members of successful clones are characterized by a high variability in their accessory genome. The abundance of successful clones might be funded in specific features of the core genome or, although not mutually exclusive, in the variability of the accessory genome. In clone C, one of the most predominant clones, the plasmid pKLC102 and the PACGI-1 genomic island are two ubiquitous accessory genetic elements. The conserved transmissible locus of protein quality control (TLPQC) at the border of PACGI-1 is a unique horizontally transferred compository element, which codes predominantly for stress-related cargo gene products such as involved in protein homeostasis. As a hallmark, most TLPQC xenologues possess a core genome equivalent. With elevated temperature tolerance as a characteristic of clone C strains, the unique P. aeruginosa and clone C specific disaggregase ClpG is a major contributor to tolerance. As other successful clones, such as PA14, do not encode the TLPQC locus, ubiquitous denominators of success, if existing, need to be identified., Molecular epidemiology of Pseudomonas aeruginosa unraveled the occurence of few predominant clones that can thrive in various habitats with clone C one of the most abundant group of closely related strains that harbor common and strain specific entities which provide unique features such as xenologues of core genome genes involved in protein homeostasis to clone C strains.
- Published
- 2020
41. A Cyclic di-GMP Network Is Present in Gram-Positive Streptococcus and Gram-Negative Proteus Species
- Author
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Rey-Ting Guo, Janja Trček, Heike Bähre, Changhan Lee, Alexey Chernobrovkin, Fengyang Li, Ying Liu, Ute Römling, Chun-Chi Chen, and Roman A. Zubarev
- Subjects
Riboswitch ,0301 basic medicine ,Cyclic di-GMP ,biology ,030106 microbiology ,Biofilm ,Heterologous ,Streptococcus suis ,GGDEF domain ,biology.organism_classification ,Proteus mirabilis ,Proteus ,Open reading frame ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,Infectious Diseases ,chemistry ,Biochemistry ,Second messenger system ,EAL domain ,Glycosyltransferase ,biology.protein ,Diguanylate cyclase ,Bacteria - Abstract
The ubiquitous cyclic di-GMP (c-di-GMP) network is highly redundant with numerous GGDEF domain proteins as diguanylate cyclases and EAL domain proteins as c-di-GMP specific phosphodiesterases comprising those domains as two of the most abundant bacterial domain superfamilies. One hallmark of the c-di-GMP network is its exalted plasticity as c-di-GMP turnover proteins can rapidly vanish from species within a genus and possess an above average transmissibility. To address the evolutionary forces of c-di-GMP turnover protein maintenance, conservation, and diversity, we investigated a Gram-positive and a Gram-negative species, which preserved only one single clearly identifiable GGDEF domain protein. Species of the family Morganellaceae of the order Enterobacterales exceptionally show disappearance of the c-di-GMP signaling network, but Proteus spp. still retained one diguanylate cyclase. As another example, in species of the bovis, pyogenes, and salivarius subgroups as well as Streptococcus suis and Streptococcus henryi of the genus Streptococcus, one candidate diguanylate cyclase was frequently identified. We demonstrate that both proteins encompass PAS (Per-ARNT-Sim)-GGDEF domains, possess diguanylate cyclase catalytic activity, and are suggested to signal via a PilZ receptor domain at the C-terminus of type 2 glycosyltransferase constituting BcsA cellulose synthases and a cellulose synthase-like protein CelA, respectively. Preservation of the ancient link between production of cellulose(-like) exopolysaccharides and c-di-GMP signaling indicates that this functionality is even of high ecological importance upon maintenance of the last remnants of a c-di-GMP signaling network in some of today's free-living bacteria.
- Published
- 2020
42. Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition
- Author
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Cameron J. Mitchell, Randall F. D'Souza, Troy L. Merry, Changhan Lee, Nina Zeng, Pinchas Cohen, Hiroshi Kumagai, David Cameron-Smith, Junxiang Wan, Jonathan S. T. Woodhead, and Christopher P. Hedges
- Subjects
Male ,Aging ,medicine.medical_specialty ,Mitochondrial DNA ,Mitochondrial-Derived Peptide MOTS-c ,muscle ,Mitochondrion ,Biology ,Healthy Aging ,Mitochondrial Proteins ,mitochondrial derived peptides ,Internal medicine ,medicine ,Humans ,Myocyte ,Muscle, Skeletal ,Gene ,Aged ,Aged, 80 and over ,Messenger RNA ,Skeletal muscle ,Cell Biology ,Middle Aged ,Mitochondria ,Open reading frame ,Endocrinology ,medicine.anatomical_structure ,RNA, Ribosomal ,Peptides ,MOTS-c ,Transcription Factors ,Research Paper - Abstract
Mitochondria putatively regulate the aging process, in part, through the small regulatory peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) that is encoded by the mitochondrial genome. Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men. Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y). Plasma MOTS-c levels only correlated with plasma in young men, was associated with markers of slow-type muscle, and associated with improved muscle quality in the older group (maximal leg-press load relative to thigh cross-sectional area). Using small mRNA assays we provide evidence that MOTS-c transcription may be regulated independently of the full length 12S rRNA gene in which it is encoded, and expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture. Our results suggest that plasma and muscle MOTS-c are differentially regulated with aging, and the increase in muscle MOTS-c expression with age is consistent with fast-to-slow type muscle fiber transition. Further research is required to determine the molecular targets of endogenous MOTS-c in human muscle but they may relate to factors that maintain muscle quality.
- Published
- 2020
43. Mitonuclear genomics and aging
- Author
-
Changhan Lee, Joseph C. Reynolds, and Conscience P. Bwiza
- Subjects
Aging ,Mitochondrial DNA ,Nuclear gene ,Longevity ,Genomics ,Bacterial genome size ,Mitochondrion ,Biology ,DNA, Mitochondrial ,Genome ,Article ,03 medical and health sciences ,Genetics ,Animals ,Humans ,Gene ,Genetics (clinical) ,030304 developmental biology ,Cell Nucleus ,0303 health sciences ,030305 genetics & heredity ,Human genetics ,Mitochondria ,Evolutionary biology ,Genome, Mitochondrial - Abstract
Our cells operate based on two distinct genomes that are enclosed in the nucleus and mitochondria. The mitochondrial genome presumably originates from endosymbiotic bacteria. With time, a large portion of the original genes in the bacterial genome is considered to have been lost or transferred to the nuclear genome, leaving a reduced 16.5 Kb circular mitochondrial DNA (mtDNA). Traditionally only 37 genes, including 13 proteins, were thought to be encoded within mtDNA, its genetic repertoire is expanding with the identification of mitochondrial-derived peptides (MDPs). The biology of aging has been largely unveiled to be regulated by genes that are encoded in the nuclear genome, whereas the mitochondrial genome remained more cryptic. However, recent studies position mitochondria and mtDNA as an important counterpart to the nuclear genome, whereby the two organelles constantly regulate each other. Thus, the genomic network that regulates lifespan and/ or healthspan is likely constituted by two unique, yet co-evolved, genomes. Here, we will discuss aspects of mitochondrial biology, especially mitochondrial communication that may add substantial momentum to aging research by accounting for both mitonuclear genomes to more comprehensively and inclusively map the genetic and molecular networks that govern aging and age-related diseases.
- Published
- 2020
44. The Effect of Public Perception of Crime formed in the Media on Fear of Crime
- Author
-
Changhan Lee, Lee Seung Hyun, and Do-Hoon Kim
- Subjects
Perception ,media_common.quotation_subject ,Vulnerability ,Cultivation theory ,Fear of crime ,Criminology ,Psychology ,media_common - Published
- 2019
45. MITOCHONDRIA: POWERHOUSE, SLAUGHTERHOUSE, AND SPEAKER OF THE HOUSE
- Author
-
Changhan Lee
- Subjects
Health (social science) ,Life-span and Life-course Studies ,Health Professions (miscellaneous) - Abstract
The nuclear and mitochondrial genomes have co-evolved since the union forged 1-2 billion years ago between our ancestral cell and free-living bacteria. The bi-genomic system is coordinated by close communication between the two genome-possessing organelles. More recently, peptides that are encoded in the mitochondrial genome have been identified and shown to communicate mitochondrial messages. In this symposium, I will discuss MOTS-c as a mitochondrial-encoded communication factor in the context of aging. MOTS-c can translocate to the nucleus under metabolic stress to directly regulate adaptive nuclear gene expression. In humans, MOTS-c levels increase in skeletal muscle and in circulation upon exercise. In mice, MOTS-c treatment significantly reversed physical decline in aged mice (22 mo.), including doubling in treadmill running time. Studies from our lab and others point to a novel class of mitochondrial-encoded longevity genes that coordinate cellular homeostasis.
- Published
- 2022
46. Investigation on the Printed CNT-Film-Based Electrochemical Sensor for Detection of Liquid Chemicals
- Author
-
Snagtae Lee, Sangsu An, Dongmin Seo, Changhan Lee, Jaeha Noh, Moonjin Lee, and Jiho Chang
- Subjects
Materials science ,electrochemical sensor ,02 engineering and technology ,Carbon nanotube ,Substrate (electronics) ,TP1-1185 ,010402 general chemistry ,Electrochemistry ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,law.invention ,printed CNT film (PCF) ,chemistry.chemical_compound ,law ,hazardous ,Limit of Detection ,carbon nanotubes (CNT) ,Electrical and Electronic Engineering ,Instrumentation ,Detection limit ,business.industry ,Nanotubes, Carbon ,Chemical technology ,Communication ,Linearity ,Response time ,noxious substances (HNS) ,Polyethylene ,021001 nanoscience & nanotechnology ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Electrochemical gas sensor ,chemistry ,Optoelectronics ,0210 nano-technology ,business - Abstract
We studied electrochemical sensors using printed carbon nanotubes (CNT) film on a polyethylene telephtalate (PET) substrate. The mechanical stability of the printed CNT film (PCF) was confirmed by using bending and Scotch tape tests. In order to determine the optimum sensor structure, a resistance-type PCF sensor (R-type PCF sensor) and a comb-type PCF sensor (C-type PCF sensor) were fabricated and compared using a diluted NH3 droplet with various concentrations. The magnitude of response, response time, sensitivity, linearity, and limit of detection (LOD) were compared, and it was concluded that C-type PCF sensor has superior performance. In addition, the feasibility of PCF electrochemical sensor was investigated using 12 kinds of hazardous and noxious substances (HNS). The detection mechanism and selectivity of the PCF sensor are discussed.
- Published
- 2021
47. GRSF1 is an age-related regulator of senescence
- Author
-
Su-Jeong Kim, Junxiang Wan, Pinchas Cohen, Changhan Lee, Kelvin Yen, and Maria Chun
- Subjects
Male ,0301 basic medicine ,Senescence ,Aging ,lcsh:Medicine ,Biology ,Mitochondrion ,Poly(A)-Binding Proteins ,Article ,03 medical and health sciences ,0302 clinical medicine ,Animals ,Humans ,Muscle, Skeletal ,Promoter Regions, Genetic ,lcsh:Science ,Gene ,Cells, Cultured ,Cellular Senescence ,Regulation of gene expression ,Gene knockdown ,Multidisciplinary ,lcsh:R ,Methylation ,DNA Methylation ,Phenotype ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Gene Expression Regulation ,Gene Knockdown Techniques ,DNA methylation ,Female ,lcsh:Q ,030217 neurology & neurosurgery - Abstract
Senescent cells that accumulate in multiple tissues with age are thought to increase pathological phenotypes. The removal of senescent cells can improve lifespan and/or healthspan in mouse models. Global hypomethylation and local hypermethylation in DNA are hallmarks of aging but it is unclear if such age-dependent methylation changes affect specific genes that regulate cellular senescence. Because mitochondria play important roles in aging and senescence, we tested if age-associated methylation changes in nuclear-encoded mitochondrial proteins were involved in regulating cellular senescence. Here, we examined the role of hypermethylation of the G-rich sequence factor 1 (GRSF1) promoter region, a mitochondrial RNA binding protein, in replication- and doxorubicin-induced cellular senescence. GRSF1 expression was lower in senescent fibroblasts, and GRSF1 knockdown induced senescence in human primary fibroblasts. These results suggest that the age-dependent hypermethylation of GRSF1 reduces its expression, which can potentially contribute to cellular senescence during aging.
- Published
- 2019
48. A metabolite binding protein moonlights as a bile-responsive chaperone
- Author
-
Kevin Wu, Changhan Lee, James C.A. Bardwell, Dawid S. Żyła, Rudi Glockshuber, and Patrick Betschinger
- Subjects
Protein Folding ,Proteome ,Protein Conformation ,Mutant ,Molecular Conformation ,Biology ,Protein aggregation ,chaperone ,protein folding ,medicine.disease_cause ,Crystallography, X-Ray ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Escherichia coli ,Bile ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,General Immunology and Microbiology ,General Neuroscience ,Binding protein ,Circular Dichroism ,Escherichia coli Proteins ,High-Throughput Nucleotide Sequencing ,Transporter ,Periplasmic space ,Articles ,Hydrogen-Ion Concentration ,Molecular Docking Simulation ,Biochemistry ,Chaperone (protein) ,Glycerophosphates ,Mutation ,biology.protein ,DNA Transposable Elements ,Protein folding ,Ampicillin ,Carrier Proteins ,030217 neurology & neurosurgery ,Gene Deletion ,Molecular Chaperones ,Protein Binding - Abstract
Bile salts are secreted into the gastrointestinal tract to aid in the absorption of lipids. In addition, bile salts show potent antimicrobial activity in part by mediating bacterial protein unfolding and aggregation. Here, using a protein folding sensor, we made the surprising discovery that the Escherichia coli periplasmic glycerol‐3‐phosphate (G3P)‐binding protein UgpB can serve, in the absence of its substrate, as a potent molecular chaperone that exhibits anti‐aggregation activity against bile salt‐induced protein aggregation. The substrate G3P, which is known to accumulate in the later compartments of the digestive system, triggers a functional switch between UgpB's activity as a molecular chaperone and its activity as a G3P transporter. A UgpB mutant unable to bind G3P is constitutively active as a chaperone, and its crystal structure shows that it contains a deep surface groove absent in the G3P‐bound wild‐type UgpB. Our work illustrates how evolution may be able to convert threats into signals that first activate and then inactivate a chaperone at the protein level in a manner that bypasses the need for ATP. ISSN:0261-4189 ISSN:1460-2075
- Published
- 2020
49. A recently isolated human commensal Escherichia coli ST10 clone member mediates enhanced thermotolerance and tetrathionate respiration on a P1 phage derived IncY plasmid
- Author
-
Haleluya Wami, Ulrich Dobrindt, Zaira Seferbekova, Heinrich Lünsdorf, Panagiotis Katikaridis, Shady Mansour Kamal, Axel Mogk, Changhan Lee, Robert Afasizhev, Annika Cimdins‐Ahne, Fengyang Li, Ute Römling, Lena Meins, Alberto J. Martín-Rodríguez, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
- Subjects
Thermotolerance ,Genomic Islands ,Locus (genetics) ,medicine.disease_cause ,Microbiology ,Genome ,thermotolerance ,03 medical and health sciences ,Oxygen Consumption ,Plasmid ,medicine ,Escherichia coli ,Humans ,Bacteriophages ,Bacteriophage P1 ,Symbiosis ,Molecular Biology ,Gene ,Research Articles ,030304 developmental biology ,0303 health sciences ,biology ,030306 microbiology ,Pseudomonas aeruginosa ,phylogenetic analysis ,biology.organism_classification ,P1 phage ,IncY plasmid ,tetrathionate respiration ,disaggregase ClpG ,Genome, Bacterial ,Bacteria ,Research Article ,Plasmids - Abstract
The ubiquitous human commensal Escherichia coli has been well investigated through its model representative E. coli K‐12. In this work, we initially characterized E. coli Fec10, a recently isolated human commensal strain of phylogroup A/sequence type ST10. Compared to E. coli K‐12, the 4.88 Mbp Fec10 genome is characterized by distinct single‐nucleotide polymorphisms and acquisition of genomic islands. In addition, E. coli Fec10 possesses a 155.86 kbp IncY plasmid, a composite element based on phage P1. pFec10 harbours multiple cargo genes such as coding for a tetrathionate reductase and its corresponding regulatory two‐component system. Among the cargo genes is also the Transmissible Locus of Protein Quality Control (TLPQC), which mediates tolerance to lethal temperatures in bacteria. The disaggregase ClpGGI of TLPQC constitutes a major determinant of the thermotolerance of E. coli Fec10. We confirmed stand‐alone disaggregation activity, but observed distinct biochemical characteristics of ClpGGI‐Fec10 compared to the nearly identical Pseudomonas aeruginosa ClpGGI‐SG17M. Furthermore, we noted a unique contribution of ClpGGI‐Fec10 to the exquisite thermotolerance of E. coli Fec10, suggesting functional differences between both disaggregases in vivo. Detection of thermotolerance in 10% of human commensal E. coli isolates hints to the successful establishment of food‐borne heat‐resistant strains in the human gut., The ubiquitousness of commensal Escherichia coli in post‐industrial humans calls for the investigation of their physiological characteristics. Thermotolerance, unconventional anaerobic respiration, and detoxification cargo genes are encoded on an IncY derived plasmid harbored by a typical member of the common ST10 clone. Thermotolerance is well represented in commensal isolates with the key disaggregase ClpGGI to be exquisitely thermostable. Fire symbol by ya‐webdesign.com.
- Published
- 2020
50. The mitochondrial-derived peptide MOTS-c promotes homeostasis in aged human placenta-derived mesenchymal stem cells in vitro
- Author
-
Jin Kyung Seok, Min Jeong Cho, Gi Jin Kim, Changhan Lee, You Shin Kim, Yu Jin Kim, Jae Ho Lee, Won Dong Yu, and Jung Jae Ko
- Subjects
0301 basic medicine ,Mitochondrial-Derived Peptide MOTS-c ,Placenta ,mTORC1 ,Mitochondrion ,Biology ,In Vitro Techniques ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Homeostasis ,Humans ,Protein kinase A ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Regeneration (biology) ,Mesenchymal stem cell ,Mesenchymal Stem Cells ,Cell Biology ,Cell biology ,Mitochondria ,030104 developmental biology ,chemistry ,Molecular Medicine ,Female ,030217 neurology & neurosurgery - Abstract
Mesenchymal stem cells (MSCs) are multipotent cells with critical roles in homeostasis and regeneration. MSCs undergo aging in response to various stresses, and this causes many diseases including degenerative disorders. Thus, regulation of aging factors is crucial for healthy aging. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) was recently reported to regulate metabolic homeostasis. Here, we investigated the restorative effects of MOTS-c on aged human placenta-derived MSCs (hPD-MSCs). MOTS-c promoted the morphology of old hPD-MSCs. MOTS-c significantly activated AMP-activated protein kinase, which is the main target pathway of MOTS-c, and inhibited its antagonistic effector mTORC1. MOTS-c considerably enhanced mitochondrial homeostasis by decreasing oxygen consumption and reactive oxygen species production. The mitochondrial state of MOTS-c-treated old hPD-MSCs was more similar to that of young hPD-MSCs than the mitochondrial state of non-treated old hPD-MSCs. MOTS-c also decreased lipid synthesis. In conclusion, we demonstrated that MOTS-c promotes homeostasis in aged hPD-MSCs.
- Published
- 2020
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