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1. Superior liver protection in mice fed total parenteral nutrition containing the novel lipid emulsion Vegaven as compared to a mixed-oil lipid emulsion containing fish oil

Author

Eliana Lucchinetti, Phing-How Lou, Alessandro Quaranta, Craig E. Wheelock, Akash Chakravarty, Martin Hersberger, Stefanie D. Krämer, and Michael Zaugg

Subjects
Total parenteral nutrition, Liver protection, Interleukin-10, Insulin, 18-Carbon n-3 fatty acids, α-linolenic acid, Nutrition. Foods and food supply, TX341-641
Abstract

Summary: Background: Mixed-oil lipid emulsion with plant-based 18-carbon n-3 fatty acids (Vegaven) elicits superior liver protection in total parenteral nutrition (TPN) compared with soybean oil-based or fish oil-based lipid emulsions. Objective: However, it is not known whether Vegaven is also superior to mixed-oil lipid emulsions containing longer-chain 20/22-carbon n-3 fatty acids derived from fish oil (SMOFlipid). Methods: Instrumented male C57BL/6NCrl mice (N=5) were subjected to a 7-day TPN with Vegaven (VEGA) or SMOFlipid (SMOF). Mice infused with 0.9% saline and free access to water and rodent diet served as controls. Tissue concentration of cytokines, indices of whole-body and hepatic glucose metabolism, markers of liver injury, and hepatic lipid mediators were measured. Results: Whole-body insulin resistance as measured by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) values was lower in VEGA compared with SMOF and accompanied by higher glucagon and lower insulin plasma levels. The abundances of hepatic insulin receptor (IR), insulin receptor substrate 2 (IRS2) as well as the tyrosine phosphorylated IRS2 were higher in VEGA when compared with SMOF, fostering higher hepatic glycogen content. Tumor necrosis factor alpha and interleukin-6 (IL6) tissue concentrations were increased in livers of mice in the SMOF group and interleukin-6 (IL6) to interleukin-10 (IL10) ratios were lower in livers and epididymal white adipose tissue of mice in the VEGA group. Direct bilirubin plasma levels were elevated in SMOF, while ALT plasma levels were similar in all groups. Profiling of hepatic lipid mediators revealed the presence of α-linolenic acid-derived hydroxy-octadecatrienoic acid species exclusively in VEGA. Conclusions: TPN with Vegaven provides superior liver protection and whole-body blood glucose control than TPN with mixed-oil lipid emulsion containing fish oil in mice.

Published
2025
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6. Novel lipid emulsion for total parenteral nutrition based on 18-carbon n–3 fatty acids elicits a superior immunometabolic phenotype in a murine model compared with standard lipid emulsions

Author

Lucchinetti, Eliana, Lou, Phing-How, Holtzhauer, Gregory, Noureddine, Nazek, Wawrzyniak, Paulina, Hartling, Ivan, Lee, Megan, Strachan, Erin, Clemente-Casares, Xavier, Tsai, Sue, Rogler, Gerhard, Krämer, Stefanie D, Hersberger, Martin, and Zaugg, Michael

Published
2022
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9. The Novel Lipid Emulsion Vegaven Is Well Tolerated and Elicits Distinct Biological Actions Compared With a Mixed-Oil Lipid Emulsion Containing Fish Oil: A Parenteral Nutrition Trial in Piglets

Author

Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Lou, Phing-How; https://orcid.org/0000-0003-2090-1132, Chakravarty, Akash; https://orcid.org/0000-0002-3022-1539, Marcolla, Camila Schultz; https://orcid.org/0000-0002-0010-4841, Pauline, Mirielle L; https://orcid.org/0000-0001-8700-0035, Wizzard, Pamela R; https://orcid.org/0000-0002-3567-1846, Field, Catherine J; https://orcid.org/0000-0001-7285-4767, Wine, Eytan; https://orcid.org/0000-0002-3458-4142, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Wales, Paul W; https://orcid.org/0000-0001-7206-735X, Turner, Justine M; https://orcid.org/0000-0002-5540-6660, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Lou, Phing-How; https://orcid.org/0000-0003-2090-1132, Chakravarty, Akash; https://orcid.org/0000-0002-3022-1539, Marcolla, Camila Schultz; https://orcid.org/0000-0002-0010-4841, Pauline, Mirielle L; https://orcid.org/0000-0001-8700-0035, Wizzard, Pamela R; https://orcid.org/0000-0002-3567-1846, Field, Catherine J; https://orcid.org/0000-0001-7285-4767, Wine, Eytan; https://orcid.org/0000-0002-3458-4142, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Wales, Paul W; https://orcid.org/0000-0001-7206-735X, Turner, Justine M; https://orcid.org/0000-0002-5540-6660, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, and Zaugg, Michael; https://orcid.org/0000-0002-2016-8973

Published
2024

10. Size of lipid emulsion droplets influences metabolism in human CD4+ T cells

Author

Noureddine, Nazek; https://orcid.org/0000-0003-0308-5807, Holtzhauer, Gregory; https://orcid.org/0000-0002-5560-2354, Wawrzyniak, Paulina; https://orcid.org/0000-0001-9641-2103, Srikanthan, Pakeerathan, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Noureddine, Nazek; https://orcid.org/0000-0003-0308-5807, Holtzhauer, Gregory; https://orcid.org/0000-0002-5560-2354, Wawrzyniak, Paulina; https://orcid.org/0000-0001-9641-2103, Srikanthan, Pakeerathan, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, and Hersberger, Martin; https://orcid.org/0000-0002-4472-329X

Published
2024

13. Endothelial Barrier Disruption by Lipid Emulsions Containing a High Amount of N3 Fatty Acids (Omegaven) but Not N6 Fatty Acids (Intralipid)

Author

Emilie Gueguen, Yasser Morsy, Michael Scharl, Stefanie D. Krämer, Michael Zaugg, Martin Hersberger, Gerhard Rogler, and Marcin Wawrzyniak

Subjects
parenteral nutrition, endothelial cells, endothelial barrier, lipid emulsions, Cytology, QH573-671
Abstract

Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven®) emulsion vs. a high amount of ω6 fatty acids (Intralipid®) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven® prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven® addition. Interestingly, the study’s findings contradict previous studies and revealed that Omegaven® at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells’ barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium.

Published
2022
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21. Crosstalk within peripheral blood mononuclear cells mediates anti-inflammatory effects of n-3 PUFA-rich lipid emulsions in parenteral nutrition

Author

Wawrzyniak, Paulina; https://orcid.org/0000-0001-9641-2103, Hubeli, Barbara, Wawrzyniak, Marcin; https://orcid.org/0000-0002-6911-8010, Noureddine, Nazek; https://orcid.org/0000-0003-0308-5807, Walberg, Asa; https://orcid.org/0000-0002-6922-8375, Scharl, Sylvie, Turina, Matthias; https://orcid.org/0000-0002-1040-3511, Scharl, Michael; https://orcid.org/0000-0002-6729-1469, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Wawrzyniak, Paulina; https://orcid.org/0000-0001-9641-2103, Hubeli, Barbara, Wawrzyniak, Marcin; https://orcid.org/0000-0002-6911-8010, Noureddine, Nazek; https://orcid.org/0000-0003-0308-5807, Walberg, Asa; https://orcid.org/0000-0002-6922-8375, Scharl, Sylvie, Turina, Matthias; https://orcid.org/0000-0002-1040-3511, Scharl, Michael; https://orcid.org/0000-0002-6729-1469, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, and Hersberger, Martin; https://orcid.org/0000-0002-4472-329X

Abstract

Background and aims: Parenteral nutrition (PN) rich in n-6 and n-3 long-chain fatty acids is used in clinical practice for nourishing patients who are unable to receive adequate nutrition through their digestive systems. In this study, we compare the effect on inflammation of the commonly used lipid emulsions Omegaven (n-3-rich) and Intralipid (n-6-rich) in human peripheral blood mononuclear cells (PBMCs).

Published
2023

25. Quantitative profiling of inflammatory and pro-resolving lipid mediators in human adolescents and mouse plasma using UHPLC-MS/MS

Author

Hartling, Ivan, Cremonesi, Alessio, Osuna, Ester, Lou, Phing-How, Lucchinetti, Eliana, Zaugg, Michael, Hersberger, Martin, and University of Zurich

Subjects
0301 basic medicine, Adolescent, Linoleic acid, Clinical Biochemistry, 610 Medicine & health, eicosanoids, LC-MS/MS, lipid mediators, oxylipins, reference value, total parenteral nutrition, 030204 cardiovascular system & hematology, Protectin D1, Pharmacology, Biochemistry, medical, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tandem Mass Spectrometry, Fatty Acids, Omega-3, Animals, Humans, Maresin, Chromatography, High Pressure Liquid, Inflammation, Chemistry, Biochemistry (medical), General Medicine, Eicosapentaenoic acid, 030104 developmental biology, 10036 Medical Clinic, Docosahexaenoic acid, Eicosanoids, lipids (amino acids, peptides, and proteins), Arachidonic acid, Docosapentaenoic acid, Resolvin
Abstract

Objectives Lipid mediators are bioactive lipids which help regulate inflammation. We aimed to develop an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify 58 pro-inflammatory and pro-resolving lipid mediators in plasma, determine preliminary reference ranges for adolescents, and investigate how total parenteral nutrition (TPN) containing omega-3 polyunsaturated fatty acid (n-3 PUFA) or n-6 PUFA based lipid emulsions influence lipid mediator concentrations in plasma. Methods Lipid mediators were extracted from plasma using SPE and measured using UHPLC-MS/MS. EDTA plasma was collected from healthy adolescents between 13 and 17 years of age to determine preliminary reference ranges and from mice given intravenous TPN for seven days containing either an n-3 PUFA or n-6 PUFA based lipid emulsion. Results We successfully quantified 43 lipid mediators in human plasma with good precision and recovery including several leukotrienes, prostaglandins, resolvins, protectins, maresins, and lipoxins. We found that the addition of methanol to human plasma after blood separation reduces post blood draw increases in 12-hydroxyeicosatetraenoic acid (12-HETE), 12-hydroxyeicosapentaenoic acid (12-HEPE), 12S-hydroxyeicosatrienoic acid (12S-HETrE), 14-hydroxydocosahexaenoic acid (14-HDHA) and thromboxane B2 (TXB2). Compared to the n-6 PUFA based TPN, the n-3 PUFA based TPN increased specialized pro-resolving mediators such as maresin 1 (MaR1), MaR2, protectin D1 (PD1), PDX, and resolvin D5 (RvD5), and decreased inflammatory lipid mediators such as leukotriene B4 (LTB4) and prostaglandin D2 (PGD2). Conclusions Our method provides an accurate and sensitive quantification of 58 lipid mediators from plasma samples, which we used to establish a preliminary reference range for lipid mediators in plasma samples of adolescents; and to show that n-3 PUFA, compared to n-6 PUFA rich TPN, leads to a less inflammatory lipid mediator profile in mice.

Published
2021
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27. Endothelial Barrier Disruption by Lipid Emulsions Containing a High Amount of N3 Fatty Acids (Omegaven) but Not N6 Fatty Acids (Intralipid)

Author

Gueguen, Emilie; https://orcid.org/0000-0002-8187-8792, Morsy, Yasser; https://orcid.org/0000-0001-8234-1877, Scharl, Michael; https://orcid.org/0000-0002-6729-1469, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, Wawrzyniak, Marcin; https://orcid.org/0000-0002-6911-8010, Gueguen, Emilie; https://orcid.org/0000-0002-8187-8792, Morsy, Yasser; https://orcid.org/0000-0001-8234-1877, Scharl, Michael; https://orcid.org/0000-0002-6729-1469, Krämer, Stefanie D; https://orcid.org/0000-0002-0426-4340, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Rogler, Gerhard; https://orcid.org/0000-0002-1733-9188, and Wawrzyniak, Marcin; https://orcid.org/0000-0002-6911-8010

Published
2022

29. Choice of Lipid Emulsion Determines Inflammation of the Gut-Liver Axis, Incretin Profile, and Insulin Signaling in a Murine Model of Total Parenteral Nutrition

Author

Stefanie D. Krämer, Paulina Wawrzyniak, Gerhard Rogler, Michael Scharl, Eliana Lucchinetti, Marcin Wawrzyniak, Phing-How Lou, Michael Zaugg, Yasser Morsy, Martin Hersberger, University of Zurich, and Zaugg, Michael

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, Hepatitis, Hyperinsulinemia, Insulin, Phospholipids, biology, Lipids, 10219 Clinic for Gastroenterology and Hepatology, Gastritis, 1305 Biotechnology, Emulsions, Parenteral Nutrition, Total, Biotechnology, medicine.medical_specialty, Incretin, 610 Medicine & health, Incretins, Glucagon, Omegaven, Interferon-gamma, 03 medical and health sciences, Fish Oils, Insulin resistance, Malabsorption Syndromes, Fatty Acids, Omega-6, Internal medicine, medicine, Animals, Muscle, Skeletal, Triglycerides, 1106 Food Science, 030109 nutrition & dietetics, Interleukin-6, business.industry, Liver, n-3 fatty acids, n-6 fatty acids, Total parenteral nutrition, medicine.disease, Soybean Oil, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, Endocrinology, Parenteral nutrition, 10036 Medical Clinic, biology.protein, Insulin Resistance, business, Food Science
Abstract

Scope The aim of this study is to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), that is, n‐3 fatty acid‐based Omegaven versus n‐6 fatty acid‐based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. Methods and results Jugular vein catheters (JVC) are placed in C57BL/6 mice and used for TPN for 7 days. Mice are randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL‐TPN, no chow), an Omegaven group (OV‐TPN, no chow), or a chow only group (without JVC). Both TPN elicite higher abundance of lipopolysaccharide binding protein in the liver, but only IL‐TPN increases interleukin‐6 and interferon‐γ, while OV‐TPN reduces interleukin‐4, monocyte chemoattractant protein‐1, and interleukin‐1α. Insulin plasma concentrations are higher in both TPN, while glucagon and glucagon‐like peptide‐1 (GLP‐1) were higher in IL‐TPN. Gluconeogenesis is increased in IL‐TPN and the nuclear profile of key metabolic transcription factors shows a liver‐protective phenotype in OV‐TPN. OV‐TPN increases insulin sensitivity in the liver and skeletal muscle. Conclusion OV‐TPN as opposed to IL‐TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by “re‐sensitizing” the liver and skeletal muscle to insulin. © 2020 Wiley-VCH GmbH. ISSN:1613-4125 ISSN:1613-4133

Published
2021

30. RNA Sequencing

Author

Eliana Lucchinetti and Michael Zaugg

Subjects
medicine.medical_specialty, Stethoscope, business.industry, General surgery, Twenty-First Century, RNA, law.invention, Anesthesiology and Pain Medicine, Pulmonology, law, Internal medicine, Pulmonary medicine, medicine, business
Published
2020
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32. The mechanism of Intralipid®-mediated cardioprotection complex IV inhibition by the active metabolite, palmitoylcarnitine, generates reactive oxygen species and activates reperfusion injury salvage kinases.

Author

Phing-How Lou, Eliana Lucchinetti, Liyan Zhang, Andreas Affolter, Marcus C Schaub, Manoj Gandhi, Martin Hersberger, Blair E Warren, Hélène Lemieux, Hany F Sobhi, Alexander S Clanachan, and Michael Zaugg

Subjects
Medicine, Science
Abstract

Intralipid® administration at reperfusion elicits protection against myocardial ischemia-reperfusion injury. However, the underlying mechanisms are not fully understood.Sprague-Dawley rat hearts were exposed to 15 min of ischemia and 30 min of reperfusion in the absence or presence of Intralipid® 1% administered at the onset of reperfusion. In separate experiments, the reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine was added either alone or with Intralipid®. Left ventricular work and activation of Akt, STAT3, and ERK1/2 were used to evaluate cardioprotection. ROS production was assessed by measuring the loss of aconitase activity and the release of hydrogen peroxide using Amplex Red. Electron transport chain complex activities and proton leak were measured by high-resolution respirometry in permeabilized cardiac fibers. Titration experiments using the fatty acid intermediates of Intralipid® palmitoyl-, oleoyl- and linoleoylcarnitine served to determine concentration-dependent inhibition of complex IV activity and mitochondrial ROS release.Intralipid® enhanced postischemic recovery and activated Akt and Erk1/2, effects that were abolished by the ROS scavenger N-(2-mercaptopropionyl)glycine. Palmitoylcarnitine and linoleoylcarnitine, but not oleoylcarnitine concentration-dependently inhibited complex IV. Only palmitoylcarnitine reached high tissue concentrations during early reperfusion and generated significant ROS by complex IV inhibition. Palmitoylcarnitine (1 µM), administered at reperfusion, also fully mimicked Intralipid®-mediated protection in an N-(2-mercaptopropionyl)-glycine -dependent manner.Our data describe a new mechanism of postconditioning cardioprotection by the clinically available fat emulsion, Intralipid®. Protection is elicited by the fatty acid intermediate palmitoylcarnitine, and involves inhibition of complex IV, an increase in ROS production and activation of the RISK pathway.

Published
2014
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33. Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.

Author

Phing-How Lou, Eliana Lucchinetti, Liyan Zhang, Andreas Affolter, Manoj Gandhi, Martin Hersberger, Blair E Warren, Hélène Lemieux, Hany F Sobhi, Alexander S Clanachan, and Michael Zaugg

Subjects
Medicine, Science
Abstract

Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1%) was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-%) served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

Published
2014
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34. Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes

Author

Tokarska-Schlattner, Malgorzata, Lucchinetti, Eliana, Zaugg, Michael, Kay, Laurence, Gratia, Severine, Guzun, Rita, Saks, Valdur, and Schlattner, Uwe

Subjects
Gene expression -- Research, Doxorubicin -- Usage, Doxorubicin -- Health aspects, Heart diseases -- Risk factors, Heart diseases -- Genetic aspects, Heart diseases -- Research, Mitochondrial DNA -- Physiological aspects, Mitochondrial DNA -- Research, Biological sciences
Abstract

Tokarska-Schlattner M, Lucchinetti E, Zaugg M, Kay L, Gratia S, Guzun R, Saks V, Schlattner U. Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes. Am J Physiol Regul Integr Comp Physiol 298: R1075-R1088, 2010. First published January 6, 2010; doi:10.1152/ajpregu.00360.2009.--Doxorubicin (DXR) belongs to the most efficient anticancer drugs. However, its clinical application is limited by the risk of severe cardiac-specific toxicity, for which an efficient treatment is missing. Underlying molecular mechanisms are not sufficiently understood so far, but nonbiased, systemic approaches can yield new clues to develop targeted therapies. Here, we applied a genome-wide transcriptome analysis to determine the early cardiac response to DXR in a model characterized earlier, that is, rat heart perfusion with 2 [micro]M DXR, leading to only mild cardiac dysfunction. Single-gene and gene set enrichment analysis of DNA microarrays yielded robust data on cardiac transcriptional reprogramming, including novel DXR-responsive pathways. Main characteristics of transcriptional reprogramming were 1) selective upregulation of individual genes or gene sets together with widespread downregulation of gene expression; 2) repression of numerous transcripts involved in cardiac stress response and stress signaling; 3) modulation of genes with cardiac remodeling capacity; 4) upregulation of 'energy-related' pathways; and 5) similarities to the transcriptional response of cancer cells. Some early responses like the induction of glycolytic and Krebs cycle genes may have compensatory function. Only minor changes in the cardiac energy status or the respiratory activity of permeabilized cardiac fibers have been observed. Other responses potentially contribute to acute and also chronic toxicity, in particular, those in stress-responsive and cardiac remodeling transcripts. We propose that a blunted response to stress and reduced 'danger signaling' is a prime component of toxic DXR action and can drive cardiac cells into pathology. anthracyclines; cardiotoxicity; gene expression; microarrays; mitochondrial function; skinned fibers doi: 10.1152/ajpregu.00360.2009.

Published
2010

35. Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria

Author

Feng, Jianhua, Lucchinetti, Eliana, Enkavi, Giray, Wang, Yi, Gehrig, Peter, Roschitzki, Bernd, Schaub, Marcus C., Tajkhorshid, Emad, Zaugg, Kathrin, and Zaugg, Michael

Subjects
Adenylic acid -- Physiological aspects, Adenylic acid -- Research, Phosphorylation -- Physiological aspects, Phosphorylation -- Genetic aspects, Phosphorylation -- Research, Protein tyrosine kinase -- Physiological aspects, Protein tyrosine kinase -- Genetic aspects, Protein tyrosine kinase -- Research, Biological sciences
Abstract

Phosphorylation of adenine nucleotide translocator 1 (ANT1) at residue Y194, which is part of the aromatic ladder located within the lumen of the carrier, critically regulates mitochondrial metabolism. Recent data support the concept that members of the Src family of nonreceptor tyrosine kinases are constitutively present in mitochondria and key to regulation of mitochondrial function. Herein, we demonstrate that site mutations of ANT1 (Y190[right arrow]F190, Y194[right arrow]F194) mimicking dephosphorylation of the aromatic ladder resulted in loss of oxidative growth and ADP/ATP exchange activity in respiration-incompetent yeast expressing mutant chimeric yN-hANT1. ANT1 is phosphorylated at Y194 by the Src family kinase members Src and Lck, and increased phosphorylation is tightly linked to reduced cell injury in preconditioned protected vs. unprotected cardiac mitochondria. Molecular dynamics simulations find the overall structure of the phosphorylated ANT1 stable, but with an increased steric flexibility in the region of the aromatic ladder, matrix loop m2, and four helix-linking regions. Combined with an analysis of the putative cytosolic salt bridge network, we reason that the effect of phosphorylation on transport is likely due to an accelerated transition between the main two conformational states (c[left right arrow]m) of the carrier during the transport cycle. Since 'aromatic signatures' are typical for other mitochondrial carrier proteins with important biological functions, our results may be more general and applicable to these carriers. mitochondrial adenosine 5'-diphosphate/adenosine 5'-triphosphate translocases; Src family tyrosine kinase; mitochondria; molecular dynamics simulations; preconditioning doi:10.1152/ajpcell.00310.2009.

Published
2010

36. Mitochondrial physiology: Gnaiger Erich et al ― MitoEAGLE Task Group

Author

Gnaiger, Erich, Aasander Frostner, Eleonor, Abdul Karim, Norwahidah, Abdel-Rahman, Engy Ali, Abumrad, Nada A, Acuna-Castroviejo, Dario, Adiele, Reginald C, Ahn, Bumsoo, Alencar, MB, Ali, Sameh S, Almeida, Angeles, Alton, Lesley, Alves, Marco G, Amati, Francesca, Amoedo, Nivea Dias, Amorim, Ricardo, Anderson, Ethan J, Andreadou, Ioanna, Antunes, Diana, Arago, Marc, Aral, Cenk, Arandarcikaite, Odeta, Arias-Reyes, Christian, Armand, Anne-Sophie, Arnould, Thierry, Avram, Vlad Florian, Axelrod, Christopher L, Bairam, Aida, Bailey, Damian M, Bajpeyi, Sudip, Bajzikova, Martina, Bakker, Barbara M, Barlow, Jonathan, Bardal, Tora, Banni, A, Bastos Sant'Anna Silva, Ana Carolina, Batterson, Philip, Battino, Maurizio, Bazil, Jason, Beard, Daniel A, Beleza, Jorge, Bednarczyk, Piotr, Bello, Fiona, Ben-Shachar, Dorit, Bento Guida, Jose Freitas, Bergdahl, Andreas, Berge, Rolf K, Bergmeister, Lisa, Bernardi, Paolo, Berridge, Michael V, Bettinazzi, Stefano, Bishop, David, Blier, Pierre U, Blindheim, Dan Filip, Boardman, Neoma T, Boetker, Hans Erik, Borchard, Sabine, Boros, Mihaly, Borsheim, Elisabet, Borras, Consuelo, Borutaite, Vilma, Botella, Javier, Bouillaud, Frederic, Bouitbir, Jamal, Boushel, Robert C, Bovard, Josh, Bravo-Sagua, Roberto, Breton, Sophie, Brown, David A, Brown, Guy C, Brown, Robert A, Brozinick, Joseph T, Buettner, Garry R, Burtscher, Johannes, Bustos, Matilde, Calabria, Elisa, Calbet, Jose A, Calzia, Enrico, Cannon, Daniel T, Cano Sanchez, Maria, Canto Alvarez, Carles, Cardinale, D, Cardoso, Luiza Helena Daltro, Carvalho, Eugenia, Casado Pinna, Marta, Cassar, Samantha, Castelo, Maria P, Castilho, Roger F, Cavalcanti-de-Albuquerque, Joao Paulo, Cecatto, Cristiane, Celen, Murat C, Cervinkova, Zuzana, Chabi, Beatrice, Chakrabarti, Lisa, Chakrabarti, Sasanka, Chaurasia, Bhagirath, Chen, Quan, Chicco, Adam J, Chinopoulos, Christos, Chowdhury, Subir K, Cizmarova, Beata, Clementi, Emilio, Coen, Paul M, Cohen, Bruce H, Coker, Robert H, Collin-Chenot, Anne, Coughlan, Melinda T, Coxito, Petro, Crisostomo, Luis, Crispim, Marcell, Crossland, Hannah, Dahdah, Norma, Dalgaard, Louise T, Dambrova, Maija, Danhelovska, Tereza, Darveau, Charles A, Darwin, Paula M, Das, Anibh M, Dash, Ranjan K, Davidova, Eliska, Davis, Michael S, Dayanidhi, Sudarshan, De Bem, Andreza Fabro, De Goede, Paul, De Palma, Clara, De Pinto, Vito, Dela, F, Dembinska-Kiec, Aldona, Detraux, Damien, Devaux, Yvan, Di Marcello, Marco, Di Paola, Floriana Jessica, Dias, Candida, Dias, Tania R, Diederich, Marc, Distefano, Giovanna, Djafarzadeh, Siamak, Doermann, Niklas, Doerrier, Carolina, Dong, Lan-Feng, Donnelly, Chris, Drahota, Zdenek, Duarte, Filipe Valente, Dubouchaud, Herve, Duchen, Michael R, Dumas, Jean-Francois, Durham, William J, Dymkowska, Dorota, Dyrstad, Sissel E, Dyson, Alex, Dzialowski, Edward M, Eaton, Simon, Ehinger, Johannes, Elmer, Eskil, Endlicher, Rene, Engin, Ayse B, Escames, Germaine, Evinova, Andrea, Ezrova, Zuzana, Falk, Marni Joy, Fell, David A, Ferdinandy, Peter, Ferko, Miroslav, Fernandez-Ortiz, Marisol, Erika, Fernandez-Vizarra, Ferreira, Julio Cesar Batista, Ferreira, Rita, Ferri, Alessandra, Festuccia, WT, Fessel, Joshua P, Filipovska, Aleksandra, Fisar, Zdenek, Fischer, Christine, Fischer, Michael, Fisher, Gordon, Fisher, Joshua J, Fontanesi, Flavia, Forbes-Hernandez, Tamara Y, Ford, Ellen, Fornaro, Mara, Fuertes Agudo, Marina, Fulton, Montana, Galina, Antonio, Galkin, Alexander, Gallee, Leon, Galli, Gina L, Gama Perez, Pau, Gan, Zhenji, Ganetzky, Rebecca, Gao, Yun, Garcia, Geovana S, Garcia-Rivas, Gerardo, Garcia-Roves, Pablo Miguel, Garcia-Souza, Luiz Felipe, Garlid, Keith D, Garrabou, Gloria, Garten, Antje, Gastaldelli, Amalia, Gayen, Jiaur, Genders, Amanda J, Genova, Maria Luisa, Giampieri, Francesca, Glatz, Jan FC, Giovarelli, Matteo, Goikoetxea Usandizaga, Naroa, Goncalo Teixeira da Silva, Rui, Goncalves, Debora Farina, Gonzalez-Armenta, Jenny L, Gonzalez-Francesqua, A, Gonzalez-Freire, Marta, Gonzalo, Hugo, Goodpaster, Bret H, Gorr, Thomas A, Gourlay, Campbell W, Grams, Bente, Granata, Cesare, Grefte, Sander, Grilo, Luis, Guarch, Meritxell Espino, Gueguen, Naig, Gumeni, Sentiljana, Haas, Clarissa B, Haavik, Jan, Hachmo, Yafit, Haendeler, Judith, Haider, Markus, Hajrulahovic, Anesa, Hamann, Andrea, Han, Jin, Han, Woo Hyun, Hancock, Chad R, Hand, Steven C, Handl, Jiri, Hansikova, Hana, Hardee, Justin P, Hargreaves, Ian P, Harper, Mary Ellen, Harrison, David K, Hassan, Hazirah, Hatakova, Zuzana, Hausenloy, Derek J, Heales, Simon JR, Heiestad, Christina, Hellgren, Kim T, Henrique, Alexandrino, Hepple, Russell T, Hernansanz-Agustin, Pablo, Hewakapuge, Sudinna, Hickey, Anthony J, Ho, Dieu Hien, Hoehn, Kyle L, Hoel, Frederik, Holland, Olivia J, Holloway, Graham P, Holzner, Lorenz, Hoppel, Charles L, Hoppeler, H, Hoppel, Florian, Houstek, Josef, Huete-Ortega, Maria, Hyrossova, Petra, Iglesias-Gonzalez, Javier, Indiveri, Cesare, Irving, Brian A, Isola, Raffaella, Iyer, Shilpa, Jackson, Christophe B, Jadiya, Pooja, Jana, Prado Fabian, Jandeleit-Dahm, K, Jang, David H, Jang, Young C, Janowska, Joanna, Jansen, Kirsten, Jansen-Duerr, Pidder, Jansone, Baiba, Jarmuszkiewicz, Wieslawa, Jaskiewicz, Anna, Jaspers, Richard T, Jedlicka, Jan, Jerome, Estaquier, Jespersen, Nichlas R, Jha, Rajan K, Joseph, Vincent, Juhasz, Laszlo, Jurczak, Michael J, Jurk, Diana, Kaambre, Tuuli, Kaczor, Jan J, Kainulainen, Heikki, Kampa, Rafal Pawel, Kandel, Sunil M, Kane, Daniel A, Kapferer, Werner, Kapnick, Senta, Kappler, Lisa, Karabatsiakis, Alexander, Karavaeva, Iuliia, Karkucinska-Wieckowska, Agnieszka, Kaur, Sarbjot, Keijer, Jaap, Keller, Markus A, Keppner, Gloria, Khamoui, Andy V, Kidere, Dita, Kilbaugh, Todd, Kim, Hyoung Kyu, Kim, Julian KS, Kimoloi, Sammy, Klepinin, Aleksandr, Klepinina, Lyudmila, Klingenspor, Martin, Klocker, Helmut, Komlódi, Timea, Kolasa, Iris, Koopman, Werner JH, Kopitar-Jerala, Natasa, Kowaltowski, Alicia J, Kozlov, Andrey V, Krajcova, Adela, Krako Jakovljevic, Nina, Kristal, Bruce S, Krycer, Jamer R, Kuang, Jujiao, Kucera, Otto, Kuka, Janis, Kwak, Hyo Bum, Kwast, Kurt, Kwon, Oh Sung, Laasmaa, Martin, Labieniec-Watala, Magdalena, Lai, Nicola, Lalic, Nebojsa M, Land, John M, Lane, Nick, Laner, Verena, Lanza, Ian R, Laouafa, Sofien, Larsen, Steen, Larsen, Terje S, Lavery, Gareth G, Lazou, Antigone, Ledo, Ana Margarida, Lee, Hong Kyu, Leeuwenburgh, Christiaan, Lehti, Maarit, Lemieux, Helene, Lenaz, Giorgio, Lerfall, Jorgen, Li, Pingan A, Li Puma, Lance, Liang, Liping, Liepins, Edgars, Lin, Chien-Te, Liu, Jiankang, Lopez, Luis C, Lucchinetti, Eliana, Ma, Tao, Macedo, Maria P, Machado, Ivo F, Maciej, Sarah, MacMillan-Crow, Lee Ann, Magalhaes, Jose, Magri, Andrea, Majtnerova, Pavlina, Makarova, Elina, Makrecka-Kuka, Marina, Malik, Afshan N, Marcouiller, Francois, Marechal, Amandine, Markova, Michaela, Markovic, Ivanka, Martin, Daniel S, Martins, Ana Dias, Martins, Joao D, Maseko, Tumisang Edward, Maull, Felicia, Mazat, Jean Pierre, McKenna, Helen T, McKenzie, Matthew, McMillan, Duncan GG, McStay, Gavin P, Menze, Michael A, Mendham, Amy, Mercer, John R, Merz, Tamara, Messina, Angela, Meszaros, Andras T, Methner, Axel, Michalak, Slawomir, Mila Guasch, Maria, Minuzzi, Luciele M, Misirkic Marjanovic, Maja, Moellering, Douglas R, Moisoi, Nicoleta, Molina, Anthony JA, Montaigne, David, Moore, Anthony L, Moore, Christy, Moreau, Kerrie, Moreira, Bruno P, Moreno-Sanchez, Rafael, Mracek, Tomas, Muccini, Anna Maria, Muntane, Jordi, Muntean, Danina M, Murray, Andrew J, Musiol, Eva, Nabben, Miranda, Nair, K Sreekumaran, Nehlin, Jan O, Nemec, Michal, Nesci, Salvatore, Neufer, P Darrell, Neuzil, Jiri, Neviere, Remi, Newsom, Sean A., Norman, Jennifer, Nozickova, Katerina, Nunes, Sara, Nuoffer, Jean-Marc, O'Brien, Kristin, O'Brien, Katie A, O'Gorman, Donal, Olgar, Yusuf, Oliveira, Ben, Oliveira, Jorge, Oliveira, Marcus F, Oliveira, Marcos Tulio, Oliveira, Pedro F, Oliveira, Paulo J, Olsen, Rolf Erik, Orynbayeva, Zulfiya, Osiewacz, Heinz D, Paez, Hector, Pak, Youngmi K, Pallotta, Maria L, Palmeira, Carlos M, Parajuli, Nirmala, Passos, Joao F, Passrugger, Manuela, Patel, Hemal H, Pavlova, Nadia, Pavlovic, Kasja, Pecina, Petr, Pedersen, Tina M, Perales, Jose Carlos, Pereira da Silva Grilo da Silva, Filomena, Pereira, Rita, Perez Valencia, Juan A, Perks, Kara L, Pesta, Dominik, Petit, Patrice X, Pettersen Nitschke, Ina Katrine, Pichaud, Nicolas, Pichler, Irene, Piel, Sarah, Pietka, Terri A, Pinho, Sonia A, Pino, Maria F, Pirkmajer, Sergej, Place, Nicolas, Plangger, Mario, Porter, Craig, Porter, Richard K, Preguica, Ines, Procaccio, Vincent, Prochownik, Edward V, Prola, Alexandre, Pulinilkunnil, Thomas, Puskarich, Michael A, Puurand, Marju, Radenkovic, Filip, Ramzan, Rabia, Rattan, Suresh IS, Reano, Simone, Reboredo, Patricia, Rees, Bernard B, Renner-Sattler, Kathrin, Rial, Eduardo, Robinson, Matthew M, Roden, Michael, Rodrigues, Ana Sofia, Rodriguez, Enrique, Rodriguez-Enriquez, Sara, Roesland, Gro Vatne, Rolo, Anabela Pinto, Ropelle, Eduardo R, Roshanravan, Baback, Rossignol, Rodrigue, Rossiter, Harry B, Rousar, Tomas, Rubelj, Ivica, Rybacka-Mossakowska, Joanna, Saada, Ann, Safaei, Zahra, Sarlak, Saharnaz, Salin, Karine, Salvadego, Desy, Sandi, Carmen, Saner, Nicholas, Santos, Diana, Sanz, Alberto, Sardao, Vilma, Sazanov, Leonid A, Scaife, Paula, Scatena, Roberto, Schartner, Melanie, Scheibye-Knudsen, Morten, Schilling, Jan M, Schlattner, Uwe, Schmitt, Sabine, Schneider Gasser, Edith Mariane, Schoenfeld, Peter, Schots, Pauke C, Schulz, Rainer, Schwarzer, Christoph, Scott, Graham R, Selman, Colin, Sendon, Pamella Marie, Shabalina, Irina G, Sharma, Pushpa, Sharma, Vipin, Shevchuk, Igor, Shirazi, Reza, Shiroma, Jonathan G, Siewiera, Karolina, Silber, Ariel M, Silva, Ana Maria, Sims, Carrie A, Singer, Dominique, Singh, Brijesh Kumar, Skolik, Robert A, Smenes, Benedikte Therese, Smith, James, Soares, Félix Alexandre Antunes, Sobotka, Ondrej, Sokolova, Inna, Solesio Torregrosa, M De la Encarnacion, Soliz, Jorge, Sonkar, Vijay K, Sova, Marina, Sowton, Alice P, Sparagna, Genevieve C, Sparks, Lauren M, Spinazzi, Marco, Stankova, Pavla, Starr, Jonathan, Stary, Creed, Stefan, Eduard, Stelfa, Gundega, Stepto, Nigel K, Stevanovic, Jelena, Stiban, Johnny, Stier, Antoine, Stocker, Roland, Storder, Julie, Sumbalova, Zuzana, Suomalainen, Wartiovaara Anu, Suravajhala, Prashanth, Svalbe, Baiba, Swerdlow, Russel H, Swiniuch, Daria, Szabo, Ildiko, Szewczyk, Adam, Szibor, Marten, Tanaka, Masashi, Tandler, Bernard, Tarnopolsky, Mark A, Tausan, Daniel, Tavernarakis, Nektarios, Tepp, Kersti, Teodoro, J, Thakkar, Himani, Thapa, Maheshwo, Thyfault, John P, Tomar, Dhanendra, Ton, Riccardo, Torp, May-Kristin, Torres-Quesada, Omar, Towheed, Atif, Treberg, Jason R, Tretter, Laszlo, Trewin, Adam J, Trifunovic, Aleksandra, Trivigno, Catherine, Tronstad, Karl Johan, Trougakos, Ioannis P, Truu, Laura, Tuncay, Erkan, Turan, Belma, Tyrrell, Daniel J, Urban, Tomas, Urner, Sofia, Valentine, Joseph Marco, Van Bergen, Nicole J, Van der Ende, Miranda, Varricchio, Frederick, Vaupel, Peter, Vella, Joanna, Vendelin, Marko, Verdaguer, IB, Vercesi, Anibal E, Vernerova, Andrea, Victor, Victor Manuel, Vieira Ligo Teixeira, Camila, Vidimce, Josif, Viel, Christian, Vieyra, Adalberto, Vilks, Karlis, Villena, Joseph A, Vincent, Vinnyfred, Vinogradov, Andrey D, Viscomi, Carlo, Vitorino, Rui Miguel Pinheiro, Vlachaki Walker, Julia, Vogt, Sebastian, Volani, Chiara, Volska, Kristine, Votion, Dominique-Marie, Vujacic-Mirski, Ksenija, Wagner, Brett A, Ward, Marie Louise, Warnsmann, Verena, Wasserman, David H, Watala, Cezary, Wei, Yau-Huei, Weinberger, Klaus M, White, Sarah, Whitfield, Jamie, Wickert, Anika, Wieckowski, Mariusz R, Wiesner, Rudolf J, Williams, Caroline M, Winwood-Smith, Hugh, Wohlgemuth, Stephanie E, Wohlwend, Martin, Wolff, Jonci Nikolai, Wrutniak-Cabello, Chantal, Wuest, Rob C I, Yokota, Takashi, Zablocki, Krzysztof, Zanon, Alessandra, Zanou, Nadege, Zaugg, Kathrin, Zaugg, Michael, Zdrazilova, Lucie, Zhang, Yong, Zhang, Yi Zhu, Zikova, Alena, Zischka, Hans, Zorzano, Antonio, Zujovic, Tijana, Zurmanova, Jitka, Zvejniece, Liga, Lagarrigue, Sylviane, Munro, Daniel, Pereira, Susana, Laranjinha, Joäo, Hecker, Matthias, Jusic, Amela, Prigione, Alessandro, Sommer, Natascha, Weissig, Volkmar, Guida, Bento, G, John G, Jones, JG, AMS - Tissue Function & Regeneration, AMS - Rehabilitation & Development, Physiology, Mito-Eagle - Evolution-Age-Gender-Lifestyle-Environment (Mito-Eagle), Oroboros Instruments, Dynamique Musculaire et Métabolisme (DMEM), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Gnaiger Erich, Aasander Frostner Eleonor, Abdul Karim Norwahidah, Abdel-Rahman Engy Ali, Abumrad Nada A, Acuna-Castroviejo Dario, Adiele Reginald C, Ahn Bumsoo, Alencar Mayke Bezerra, Ali Sameh S, Almeida Angeles, Alton Lesley, Alves Marco G, Amati Francesca, Amoedo Nivea Dias, Amorim Ricardo, Anderson Ethan J, Andreadou Ioanna, Antunes Diana, Arago Marc, Aral Cenk, Arandarcikaite Odeta, Arias-Reyes Christian, Armand Anne-Sophie, Arnould Thierry, Avram Vlad F, Axelrod Christopher L, Bailey Damian M, Bairam Aida, Bajpeyi Sudip, Bajzikova Martina, Bakker Barbara M, Banni Aml, Bardal Tora, Barlow J, Bastos Sant'Anna Silva Ana Carolina, Batterson Philip M, Battino Maurizio, Bazil Jason N, Beard Daniel A, Bednarczyk Piotr, Beleza Jorge, Bello Fiona, Ben-Shachar Dorit, Bento Guida Jose Freitas, Bergdahl Andreas, Berge Rolf K, Bergmeister Lisa, Bernardi Paolo, Berridge Michael V, Bettinazzi Stefano, Bishop David J, Blier Pierre U, Blindheim Dan Filip, Boardman Neoma T, Boetker Hans Erik, Borchard Sabine, Boros Mihaly, Boersheim Elisabet, Borras Consuelo, Borutaite Vilma, Botella Javier, Bouillaud Frederic, Bouitbir Jamal, Boushel Robert C, Bovard Josh, Bravo-Sagua Roberto, Breton Sophie, Brown David A, Brown Guy C, Brown Robert Andrew, Brozinick Joseph T, Buettner Garry R, Burtscher Johannes, Bustos Matilde, Calabria Elisa, Calbet Jose AL, Calzia Enrico, Cannon Daniel T, Cano Sanchez Maria Consolacion, Canto Alvarez Carles, Cardinale Daniele A, Cardoso Luiza HD, Carvalho Eugenia, Casado Pinna Marta, Cassar Samantha, Castelo Rueda Maria Paulina, Castilho Roger F, Cavalcanti-de-Albuquerque Joao Paulo, Cecatto Cristiane, Celen Murat C, Cervinkova Zuzana, Chabi Beatrice, Chakrabarti Lisa, Chakrabarti Sasanka, Chaurasia Bhagirath, Chen Quan, Chicco Adam J, Chinopoulos Christos, Chowdhury Subir Kumar, Cizmarova Beata, Clementi Emilio, Coen Paul M, Cohen Bruce H, Coker Robert H, Collin-Chenot Anne, Coughlan Melinda T, Coxito Pedro, Crisostomo Luis, Crispim Marcell, Crossland Hannah, Dahdah Norma Ramon, Dalgaard Louise T, Dambrova Maija, Danhelovska Tereza, Darveau Charles-A, Darwin Paula M, Das Anibh Martin, Dash Ranjan K, Davidova Eliska, Davis Michael S, Dayanidhi Sudarshan, De Bem Andreza Fabro, De Goede Paul, De Palma Clara, De Pinto Vito, Dela Flemming, Dembinska-Kiec Aldona, Detraux Damian, Devaux Yvan, Di Marcello Marco, Di Paola Floriana Jessica, Dias Candida, Dias Tania R, Diederich Marc, Distefano Giovanna, Djafarzadeh Siamak, Doermann Niklas, Doerrier Carolina, Dong Lan-Feng, Donnelly Chris, Drahota Zdenek, Duarte Filipe Valente, Dubouchaud Herve, Duchen Michael R, Dumas Jean-Francois, Durham William J, Dymkowska Dorota, Dyrstad Sissel E, Dyson Alex, Dzialowski Edward M, Eaton Simon, Ehinger Johannes K, Elmer Eskil, Endlicher Rene, Engin Ayse Basak, Escames Germaine, Evinova Andrea, Ezrova Zuzana, Falk Marni J, Fell David A, Ferdinandy Peter, Ferko Miroslav, Fernandez-Ortiz Marisol, Fernandez-Vizarra Erika, Ferreira Julio Cesar B, Ferreira Rita Maria P, Ferri Alessandra, Fessel Joshua Patrick, Festuccia William T, Filipovska Aleksandra, Fisar Zdenek, Fischer Christine, Fischer Michael J, Fisher Gordon, Fisher Joshua J, Fontanesi Flavia, Forbes-Hernandez Tamara Y, Ford Ellen, Fornaro Mara, Fuertes Agudo Marina, Fulton Montana, Galina Antonio, Galkin Alexander, Gallee Leon, Galli Gina L J, Gama Perez Pau, Gan Zhenji, Ganetzky Rebecca, Gao Yun, Garcia Geovana S, Garcia-Rivas Gerardo, Garcia-Roves Pablo Miguel, Garcia-Souza Luiz F, Garlid Keith D, Garrabou Gloria, Garten Antje, Gastaldelli Amalia, Gayen Jiaur, Genders Amanda J, Genova Maria Luisa, Giampieri Francesca, Giovarelli Matteo, Glatz Jan FC, Goikoetxea Usandizaga Naroa, Goncalo Teixeira da Silva Rui, Goncalves Debora Farina, Gonzalez- Armenta Jenny L, Gonzalez-Franquesa Alba, Gonzalez-Freire Marta, Gonzalo Hugo, Goodpaster Bret H, Gorr Thomas A, Gourlay Campbell W, Grams Bente, Granata Cesare, Grefte Sander, Grilo Luis, Guarch Meritxell Espino, Gueguen Naig, Gumeni Sentiljana, Haas Clarissa, Haavik Jan, Hachmo Yafit, Haendeler Judith, Haider Markus, Hajrulahovic Anesa, Hamann Andrea, Han Jin, Han Woo Hyun, Hancock Chad R, Hand Steven C, Handl Jiri, Hansikova Hana, Hardee Justin P, Hargreaves Iain P, Harper Mary- Ellen, Harrison David K, Hassan Hazirah, Hatokova Zuzana, Hausenloy Derek J, Heales Simon JR, Hecker Matthias, Heiestad Christina, Hellgren Kim T, Henrique Alexandrino, Hepple Russell T, Hernansanz- Agustin Pablo, Hewakapuge Sudinna, Hickey Anthony J, Ho Dieu Hien, Hoehn Kyle L, Hoel Fredrik, Holland Olivia J, Holloway Graham P, Holzner Lorenz, Hoppel Charles L, Hoppel Florian, Hoppeler Hans, Houstek Josef, Huete-Ortega Maria, Hyrossova Petra, Iglesias-Gonzalez Javier, Indiveri Cesare, Irving Brian A, Isola Raffaella, Iyer Shilpa, Jackson Christopher Benjamin, Jadiya Pooja, Jana Prado Fabian, Jandeleit-Dahm Karin, Jang David H, Jang Young Charles, Janowska Joanna, Jansen Kirsten M, Jansen-Duerr Pidder, Jansone Baiba, Jarmuszkiewicz Wieslawa, Jaskiewicz Anna, Jaspers Richard T, Jedlicka Jan, Jerome Estaquier, Jespersen Nichlas Riise, Jha Rajan Kumar, Jones John G, Joseph Vincent, Juhasz Laszlo, Jurczak Michael J, Jurk Diana, Jusic Amela, Kaambre Tuuli, Kaczor Jan Jacek, Kainulainen Heikki, Kampa Rafal Pawel, Kandel Sunil Mani, Kane Daniel A, Kapferer Werner, Kapnick Senta, Kappler Lisa, Karabatsiakis Alexander, Karavaeva Iuliia, Karkucinska-Wieckowska Agnieszka, Kaur Sarbjot, Keijer Jaap, Keller Markus A, Keppner Gloria, Khamoui Andy V, Kidere Dita, Kilbaugh Todd, Kim Hyoung Kyu, Kim Julian KS, Kimoloi Sammy, Klepinin Aleksandr, Klepinina Lyudmila, Klingenspor Martin, Klocker Helmut, Kolassa Iris, Komlodi Timea, Koopman Werner JH, Kopitar-Jerala Natasa, Kowaltowski Alicia J, Kozlov Andrey V, Krajcova Adela, Krako Jakovljevic Nina, Kristal Bruce S, Krycer James R, Kuang Jujiao, Kucera Otto, Kuka Janis, Kwak Hyo Bum, Kwast Kurt E, Kwon Oh Sung, Laasmaa Martin, Labieniec-Watala Magdalena, Lagarrigue Sylviane, Lai Nicola, Lalic Nebojsa M, Land John M, Lane Nick, Laner Verena, Lanza Ian R, Laouafa Sofien, Laranjinha Joao, Larsen Steen, Larsen Terje S, Lavery Gareth G, Lazou Antigone, Ledo Ana Margarida, Lee Hong Kyu, Leeuwenburgh Christiaan, Lehti Maarit, Lemieux Helene, Lenaz Giorgio, Lerfall Joergen, Li Pingan Andy, Li Puma Lance, Liang Liping, Liepins Edgars, Lin Chien-Te, Liu Jiankang, Lopez Garcia Luis Carlos, Lucchinetti Eliana, Ma Tao, Macedo Maria Paula, Machado Ivo F, Maciej Sarah, MacMillan-Crow Lee Ann, Magalhaes Jose, Magri Andrea, Majtnerova Pavlina, Makarova Elina, Makrecka-Kuka Marina, Malik Afshan N, Marcouiller Francois, Marechal Amandine, Markova Michaela, Markovic Ivanka, Martin Daniel S, Martins Ana Dias, Martins Joao D, Maseko Tumisang Edward, Maull Felicia, Mazat Jean-Pierre, McKenna Helen T, McKenzie Matthew, McMillan Duncan GG, McStay Gavin P, Mendham Amy, Menze Michael A, Mercer John R, Merz Tamara, Messina Angela, Meszaros Andras, Methner Axel, Michalak Slawomir, Mila Guasch Maria, Minuzzi Luciele M, Misirkic Marjanovic Maja, Moellering Douglas R, Moisoi Nicoleta, Molina Anthony JA, Montaigne David, Moore Anthony L, Moore Christy, Moreau Kerrie, Moreira Bruno P, Moreno-Sanchez Rafael, Mracek Tomas, Muccini Anna Maria, Munro Daniel, Muntane Jordi, Muntean Danina M, Murray Andrew James, Musiol Eva, Nabben Miranda, Nair K Sreekumaran, Nehlin Jan O, Nemec Michal, Nesci Salvatore, Neufer P Darrell, Neuzil Jiri, Neviere Remi, Newsom Sean A, Norman Jennifer, Nozickova Katerina, Nunes Sara, Nuoffer Jean-Marc, O'Brien Kristin, O'Brien Katie A, O'Gorman Donal, Olgar Yusuf, Oliveira Ben, Oliveira Jorge, Oliveira Marcus F, Oliveira Marcos Tulio, Oliveira Pedro Fontes, Oliveira Paulo J, Olsen Rolf Erik, Orynbayeva Zulfiya, Osiewacz Heinz D, Paez Hector, Pak Youngmi Kim, Pallotta Maria Luigia, Palmeira Carlos, Parajuli Nirmala, Passos Joao F, Passrugger Manuela, Patel Hemal H, Pavlova Nadia, Pavlovic Kasja, Pecina Petr, Pedersen Tina M, Perales Jose Carles, Pereira da Silva Grilo da Silva Filomena, Pereira Rita, Pereira Susana P, Perez Valencia Juan Alberto, Perks Kara L, Pesta Dominik, Petit Patrice X, Pettersen Nitschke Ina Katrine, Pichaud Nicolas, Pichler Irene, Piel Sarah, Pietka Terri A, Pinho Sonia A, Pino Maria F, Pirkmajer Sergej, Place Nicolas, Plangger Mario, Porter Craig, Porter Richard K, Preguica Ines, Prigione Alessandro, Procaccio Vincent, Prochownik Edward V, Prola Alexandre, Pulinilkunnil Thomas, Puskarich Michael A, Puurand Marju, Radenkovic Filip, Ramzan Rabia, Rattan Suresh IS, Reano Simone, Reboredo-Rodriguez Patricia, Rees Bernard B, Renner-Sattler Kathrin, Rial Eduardo, Robinson Matthew M, Roden Michael, Rodrigues Ana Sofia, Rodriguez Enrique, Rodriguez-Enriquez Sara, Roesland Gro Vatne, Rohlena Jakub, Rolo Anabela Pinto, Ropelle Eduardo R, Roshanravan Baback, Rossignol Rodrigue, Rossiter Harry B, Rousar Tomas, Rubelj Ivica, Rybacka-Mossakowska Joanna, Saada Reisch Ann, Safaei Zahra, Salin Karine, Salvadego Desy, Sandi Carmen, Saner Nicholas, Santos Diana, Sanz Alberto, Sardao Vilma, Sarlak Saharnaz, Sazanov Leonid A, Scaife Paula, Scatena Roberto, Schartner Melanie, Scheibye-Knudsen Morten, Schilling Jan M, Schlattner Uwe, Schmitt Sabine, Schneider Gasser Edith Mariane, Schoenfeld Peter, Schots Pauke C, Schulz Rainer, Schwarzer Christoph, Scott Graham R, Selman Colin, Sendon Pamella Marie, Shabalina Irina G, Sharma Pushpa, Sharma Vipin, Shevchuk Igor, Shirazi Reza, Shiroma Jonathan G, Siewiera Karolina, Silber Ariel M, Silva Ana Maria, Sims Carrie A, Singer Dominique, Singh Brijesh Kumar, Skolik Robert A, Smenes Benedikte Therese, Smith James, Soares Felix Alexandre Antunes, Sobotka Ondrej, Sokolova Inna, Solesio Maria E, Soliz Jorge, Sommer Natascha, Sonkar Vijay K, Sova Marina, Sowton Alice P, Sparagna Genevieve C, Sparks Lauren M, Spinazzi Marco, Stankova Pavla, Starr Jonathan, Stary Creed, Stefan Eduard, Stelfa Gundega, Stepto Nigel K, Stevanovic Jelena, Stiban Johnny, Stier Antoine, Stocker Roland, Storder Julie, Sumbalova Zuzana, Suomalainen Anu, Suravajhala Prashanth, Svalbe Baiba, Swerdlow Russell H, Swiniuch Daria, Szabo Ildiko, Szewczyk Adam, Szibor Marten, Tanaka Masashi, Tandler Bernard, Tarnopolsky Mark A, Tausan Daniel, Tavernarakis Nektarios, Teodoro Joao Soeiro, Tepp Kersti, Thakkar Himani, Thapa Maheshwor, Thyfault John P, Tomar Dhanendra, Ton Riccardo, Torp May-Kristin, Torres-Quesada Omar, Towheed Atif, Treberg Jason R, Tretter Laszlo, Trewin Adam J, Trifunovic Aleksandra, Trivigno Catherine, Tronstad Karl Johan, Trougakos Ioannis P, Truu Laura, Tuncay Erkan, Turan Belma, Tyrrell Daniel J, Urban Tomas, Urner Sofia, Valentine Joseph Marco, Van Bergen Nicole J, Van der Ende Miranda, Varricchio Frederick, Vaupel Peter, Vella Joanna, Vendelin Marko, Vercesi Anibal E, Verdaguer Ignasi Bofill, Vernerova Andrea, Victor Victor Manuel, Vieira Ligo Teixeira Camila, Vidimce Josif, Viel Christian, Vieyra Adalberto, Vilks Karlis, Villena Josep A, Vincent Vinnyfred, Vinogradov Andrey D, Viscomi Carlo, Vitorino Rui Miguel Pinheiro, Vlachaki Walker Julia, Vogt Sebastian, Volani Chiara, Volska Kristine, Votion Dominique-Marie, Vujacic-Mirski Ksenija, Wagner Brett A, Ward Marie Louise, Warnsmann Verena, Wasserman David H, Watala Cezary, Wei Yau-Huei, Weinberger Klaus M, Weissig Volkmar, White Sarah Haverty, Whitfield Jamie, Wickert Anika, Wieckowski Mariusz R, Wiesner Rudolf J, Williams Caroline M, Winwood-Smith Hugh, Wohlgemuth Stephanie E, Wohlwend Martin, Wolff Jonci Nikolai, Wrutniak-Cabello Chantal, Wuest Rob CI, Yokota Takashi, Zablocki Krzysztof, Zanon Alessandra, Zanou Nadege, Zaugg Kathrin, Zaugg Michael, Zdrazilova Lucie, Zhang Yong, Zhang Yizhu, Zikova Alena, Zischka Hans, Zorzano Antonio, Zujovic Tijana, Zurmanova Jitka, Zvejniece Liga

Subjects
uncoupling, MitoPedia: Respiratory states, SI - The International System of Units, IUPAC, Coupling control, Mitochondrial preparations, Protonmotive force, Uncoupling, Oxidative phosphorylation, Phosphorylation efficiency, Electron transfer-pathway, LEAK-respiration, Residual oxygen consumption, Normalization of rate, Flow, Flux, Flux control ratio, Mitochondrial marker, Cell count, Oxygen, [SDV]Life Sciences [q-bio], coupling control, protonmotive force, oxidative phosphorylation, mitochondrial respiratory control, State 4, electron transfer, State 2, State 3, Mitochondrial physiology, residual oxygen consumption, flux, normalization, ion leak and slip compensatory state, efficiency, electron transfer system, flow, mitochondrial physiology, oxygen, mitochondrial preparations, proton leak
Abstract

As the knowledge base and importance of mitochondrial physiology to evolution, health and diseaseexpands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followthe latest SI guidelines and those of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute BEC 2020.1 doi:10.26124/bec:2020-0001.v1www.bioenergetics-communications.org3of 44to reproducibility between laboratories and thussupport the development of datarepositoriesof mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

Published
2020
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38. Diet and Inflammatory Bowel Disease: What Quality Standards Should Be Applied in Clinical and Laboratory Studies?

Author

Martin Hersberger, Gerhard Rogler, Luc Biedermann, Marianne R. Spalinger, Michael Scharl, Michael Zaugg, Bahtiyar Yilmaz, Hans H Herfarth, Philipp Schreiner, University of Zurich, and Rogler, Gerhard

Subjects
0301 basic medicine, medicine.medical_specialty, media_common.quotation_subject, MEDLINE, Dietary factors, 610 Medicine & health, Inflammatory bowel disease, digestive system, 03 medical and health sciences, Intestinal inflammation, Epidemiology, medicine, Animals, Humans, Quality (business), In patient, Intensive care medicine, 1106 Food Science, media_common, Clinical Trials as Topic, 030109 nutrition & dietetics, business.industry, medicine.disease, Colitis, Inflammatory Bowel Diseases, Intervention studies, digestive system diseases, Diet, Gastrointestinal Microbiome, Disease Models, Animal, 030104 developmental biology, 10219 Clinic for Gastroenterology and Hepatology, 10036 Medical Clinic, 1305 Biotechnology, business, Biotechnology, Food Science
Abstract

Many patients suffering from inflammatory bowel disease (IBD) follow restrictive diets, as many respective recommendations circulate. Efforts are made to evaluate and summarize the published information, for example, in a recent consensus manuscript by the International Organization for the Study of IBD (IOIBD). However, the standards that should be applied to make claims about dietary effects are poorly defined. In this manuscript, the scientific basis of recommendations for nutritional interventions in IBD is analyzed. Epidemiological evidence on diet in IBD is always biased by numerous factors, and the number of robust dietary intervention studies is limited due to methodological difficulties. Therefore, animal models are used to test hypotheses with respect to dietary factors and intestinal inflammation. Naturally, animal models have limitations, and knowledge of key characteristics of colitis animal models is crucial to understand their advantages and disadvantages. In recent years the important role of the microbiota for IBD and dietary factors has been discovered. Microbiota data are added to many publications on IBD and nutrition. The quality of those data varies largely. Subsequently, quality standards for microbiota analyses also are discussed. Finally, quality requirements to be applied on recommendations for dietary changes in patients with IBD are suggested.

Published
2021
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39. The ER chaperone calnexin controls mitochondrial positioning and respiration

Author

Michael Overduin, Megan C. Yap, Sandra Burgstaller, Klaus Ballanyi, Paul LaPointe, Eliana Lucchinetti, Nasser Tahbaz, Tomás Gutiérrez, Jianwei Shuai, Roland Malli, Helmut Bischof, Thomas Simmen, Hong Qi, Pascal Mercier, Michael Zaugg, Phing-How Lou, and Leanne Milburn

Subjects
SERCA, Bioenergetics, Calnexin, ATPase, Oxidative phosphorylation, Mitochondrion, Endoplasmic Reticulum, Biochemistry, Oxidative Phosphorylation, Sarcoplasmic Reticulum Calcium-Transporting ATPases, 03 medical and health sciences, Mice, 0302 clinical medicine, Oxygen Consumption, Animals, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Endoplasmic reticulum, Cell Biology, Cell biology, Mitochondria, 030220 oncology & carcinogenesis, biology.protein, Flux (metabolism), Glycolysis
Abstract

Chaperones in the endoplasmic reticulum (ER) control the flux of Ca2+ ions into mitochondria, thereby increasing or decreasing the energetic output of the oxidative phosphorylation pathway. An example is the abundant ER lectin calnexin, which interacts with sarco/endoplasmic reticulum Ca2+ ATPase (SERCA). We found that calnexin stimulated the ATPase activity of SERCA by maintaining its redox state. This function enabled calnexin to control how much ER Ca2+ was available for mitochondria, a key determinant for mitochondrial bioenergetics. Calnexin-deficient cells compensated for the loss of this function by partially shifting energy generation to the glycolytic pathway. These cells also showed closer apposition between the ER and mitochondria. Calnexin therefore controls the cellular energy balance between oxidative phosphorylation and glycolysis.

Published
2020

40. Diabetic Rat Hearts Show More Favorable Metabolic Adaptation to Omegaven Containing High Amounts of n3 Fatty Acids Than Intralipid Containing n6 Fatty Acids

Author

Michael Zaugg, Alexander S. Clanachan, Eliana Lucchinetti, Phing-How Lou, Martin Hersberger, and University of Zurich

Subjects
Male, medicine.medical_specialty, Diabetic Cardiomyopathies, Dietary Sugars, medicine.medical_treatment, 610 Medicine & health, Fructose, Omegaven, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Fish Oils, 030202 anesthesiology, Internal medicine, Medicine, Animals, Glycolysis, Myocytes, Cardiac, Glycogen synthase, Phospholipids, Triglycerides, chemistry.chemical_classification, biology, business.industry, Insulin, Albumin, Fatty acid, medicine.disease, Soybean Oil, Insulin receptor, Disease Models, Animal, Endocrinology, Anesthesiology and Pain Medicine, chemistry, 10036 Medical Clinic, biology.protein, Emulsions, Insulin Resistance, business, Energy Metabolism, Oxidation-Reduction, 030217 neurology & neurosurgery
Abstract

While Omegaven, an omega-3 (n3) fatty acid-based lipid emulsion, fosters insulin signaling in healthy hearts, it is unknown whether beneficial metabolic effects occur in insulin-resistant diabetic hearts.Diabetic hearts from fructose-fed Sprague-Dawley rats were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to Intralipid (25 and 100 µM), Omegaven (25 and 100 µM), or no emulsion (insulin alone) for 60 minutes. Glycolysis, glycogen synthesis, and glucose oxidation were measured with the radioactive tracers [5-H]glucose and [U-C]glucose. Central carbon metabolites, acyl-coenzyme A species (acyl-CoAs), ketoacids, purines, phosphocreatine, acylcarnitines, and acyl composition of phospholipids were measured with mass spectrometry.Diabetic hearts showed no response to insulin with regard to glycolytic flux, consistent with insulin resistance. Addition of either lipid emulsion did not alter this response but unexpectedly increased glucose oxidation (ratio of treatment/baseline, ie, fold change): no insulin 1.3 (0.3) [mean (standard deviation)], insulin alone 1.4 (0.4), insulin + 25 µM Intralipid 1.8 (0.5), insulin + 100 µM Intralipid 2.2 (0.4), P.001; no insulin 1.3 (0.3), insulin alone 1.4 (0.4), insulin + 25 µM Omegaven 2.3 (0.5) insulin + 100 µM Omegaven 1.9 (0.4), P.001. Intralipid treatment led to accumulation of acylcarnitines as a result of the released linoleic acid (C18:2-n6) and enhanced its integration into phospholipids, consistent with incomplete or impaired β-oxidation necessitating a compensatory increase in glucose oxidation. Accumulation of acylcarnitines was also associated with a higher nicotinamide adenine dinucleotide reduced/oxidized (NADH/NAD) ratio, which inhibited pyruvate dehydrogenase (PDH), and resulted in excess lactate production. In contrast, Omegaven-treated hearts showed no acylcarnitine accumulation, low malonyl-CoA concentrations consistent with activated β-oxidation, and elevated PDH activity and glucose oxidation, together indicative of a higher metabolic rate possibly by substrate cycling.Omegaven is the preferred lipid emulsion for insulin-resistant diabetic hearts.

Published
2020

41. Quantitative profiling of inflammatory and pro-resolving lipid mediators in human adolescents and mouse plasma using UHPLC-MS/MS

Author

Hartling, Ivan; https://orcid.org/0000-0002-6309-7984, Cremonesi, Alessio; https://orcid.org/0000-0002-1524-4169, Osuna, Ester; https://orcid.org/0000-0001-7706-6102, Lou, Phing-How; https://orcid.org/0000-0003-2090-1132, Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, Hersberger, Martin; https://orcid.org/0000-0002-4472-329X, Hartling, Ivan; https://orcid.org/0000-0002-6309-7984, Cremonesi, Alessio; https://orcid.org/0000-0002-1524-4169, Osuna, Ester; https://orcid.org/0000-0001-7706-6102, Lou, Phing-How; https://orcid.org/0000-0003-2090-1132, Lucchinetti, Eliana; https://orcid.org/0000-0003-3338-1279, Zaugg, Michael; https://orcid.org/0000-0002-2016-8973, and Hersberger, Martin; https://orcid.org/0000-0002-4472-329X

Abstract

Objectives Lipid mediators are bioactive lipids which help regulate inflammation. We aimed to develop an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify 58 pro-inflammatory and pro-resolving lipid mediators in plasma, determine preliminary reference ranges for adolescents, and investigate how total parenteral nutrition (TPN) containing omega-3 polyunsaturated fatty acid (n-3 PUFA) or n-6 PUFA based lipid emulsions influence lipid mediator concentrations in plasma. Methods Lipid mediators were extracted from plasma using SPE and measured using UHPLC-MS/MS. EDTA plasma was collected from healthy adolescents between 13 and 17 years of age to determine preliminary reference ranges and from mice given intravenous TPN for seven days containing either an n-3 PUFA or n-6 PUFA based lipid emulsion. Results We successfully quantified 43 lipid mediators in human plasma with good precision and recovery including several leukotrienes, prostaglandins, resolvins, protectins, maresins, and lipoxins. We found that the addition of methanol to human plasma after blood separation reduces post blood draw increases in 12-hydroxyeicosatetraenoic acid (12-HETE), 12-hydroxyeicosapentaenoic acid (12-HEPE), 12S-hydroxyeicosatrienoic acid (12S-HETrE), 14-hydroxydocosahexaenoic acid (14-HDHA) and thromboxane B2 (TXB2). Compared to the n-6 PUFA based TPN, the n-3 PUFA based TPN increased specialized pro-resolving mediators such as maresin 1 (MaR1), MaR2, protectin D1 (PD1), PDX, and resolvin D5 (RvD5), and decreased inflammatory lipid mediators such as leukotriene B4 (LTB4) and prostaglandin D2 (PGD2). Conclusions Our method provides an accurate and sensitive quantification of 58 lipid mediators from plasma samples, which we used to establish a preliminary reference range for lipid mediators in plasma samples of adolescents; and to show that n-3 PUFA, compared to n-6 PUFA rich TPN, leads to a less inflammatory lipid mediator profile in mice.

Published
2021

42. Differential Effects of Anesthetics and Opioid Receptor Activation on Cardioprotection Elicited by Reactive Oxygen Species–Mediated Postconditioning in Sprague-Dawley Rat Hearts

Author

Alexander S. Clanachan, Eliana Lucchinetti, Phing-How Lou, Michael Zaugg, and Manoj Gandhi

Subjects
Male, medicine.drug_class, Remifentanil, Ischemia, Myocardial Reperfusion Injury, 030204 cardiovascular system & hematology, Pharmacology, Sevoflurane, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Opioid receptor, Animals, Medicine, Ischemic Postconditioning, Propofol, chemistry.chemical_classification, Cardioprotection, Reactive oxygen species, business.industry, Heart, Isolated Heart Preparation, medicine.disease, Rats, Cardiovascular physiology, Analgesics, Opioid, Anesthesiology and Pain Medicine, chemistry, Anesthetics, Inhalation, Receptors, Opioid, Reactive Oxygen Species, business, Anesthetics, Intravenous, medicine.drug
Abstract

BACKGROUND Despite an array of cardioprotective interventions identified in preclinical models of ischemia-reperfusion (IR) injury, successful clinical translation has not been achieved. This study investigated whether drugs routinely used in clinical anesthesia influence cardioprotective effectiveness by reducing effects of reactive oxygen species (ROS), upstream triggers of cardioprotective signaling. Effects of propofol, sevoflurane, or remifentanil were compared on postischemic functional recovery induced by ROS-mediated postconditioning with Intralipid. METHODS Recovery of left ventricular (LV) work, an index of IR injury, was measured in isolated Sprague-Dawley rat hearts subjected to global ischemia (20 minutes) and reperfusion (30 minutes). Hearts were either untreated or were treated with postconditioning with Intralipid (1%, throughout reperfusion). Propofol (10 μM), sevoflurane (2 vol%), remifentanil (3 nM), or combinations thereof were administered peri-ischemically (before and during IR). The effects of anesthetics on ROS production were measured in LV cardiac fibers by Amplex Red assay under phosphorylating and nonphosphorylating conditions. RESULTS Recovery of LV work (expressed as percentage of the preischemic value ± standard deviation) in untreated hearts was poor (20% ± 7%) and was improved by Intralipid postconditioning (58% ± 8%, P = .001). In the absence of Intralipid postconditioning, recovery of LV work was enhanced by propofol (28% ± 9%, P = .049), sevoflurane (49% ± 5%, P < .001), and remifentanil (51% ± 6%, P < .001). The benefit of Intralipid postconditioning was abolished by propofol (33% ± 10%, P < .001), but enhanced by sevoflurane (80% ± 7%, P < .001) or remifentanil (80% ± 9%, P < .001). ROS signaling in LV fibers was abolished by propofol, but unaffected by sevoflurane or remifentanil. We conclude that propofol abolishes ROS-mediated Intralipid postconditioning by acting as a ROS scavenger. Sevoflurane and remifentanil are protective per se and provide additive cardioprotection to ROS-mediated cardioprotection. CONCLUSIONS These divergent effects of routinely used drugs in clinical anesthesia may influence the translatability of cardioprotective therapies such as Intralipid postconditioning.

Published
2018
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44. Acute toxicity of doxorubicin on isolated perfused heart: response of kinases regulating energy supply

Author

Tokarska-Schlattner, Malgorzata, Zaugg, Michael, da Silva, Rafaela, Lucchinetti, Eliana, Schaub, Marcus C., Wallimann, Theo, and Schlattner, Uwe

Subjects
Doxorubicin -- Complications and side effects, Antimitotic agents -- Complications and side effects, Antineoplastic agents -- Complications and side effects, Anthracyclines -- Complications and side effects, Protein kinases, Metabolism, Homeostasis, Creatine kinase, Biological sciences
Abstract

Doxorubicin (DXR) is a widely used and efficient anticancer drug. However, its application is limited by the risk of severe cardiotoxicity. Impairment of cardiac high-energy phosphate homeostasis is an important manifestation of both acute and chronic DXR cardiotoxic action. Using the Langendorff model of the perfused rat heart, we characterized the acute effects of 1-h perfusion with 2 or 20 [micro]M DXR on two key kinases in cardiac energy metabolism, creatine kinase (CK) and AMP-activated protein kinase (AMPK), and related them to functional responses of the perfused heart and structural integrity of the contractile apparatus as well as drug accumulation in cardiomyocytes. DXR-induced changes in CK were dependent on the isoenzyme, with a shift in protein levels of cytosolic isoenzymes from muscle-type CK to brain-type CK, and a destabilization of octamers of the mitochondrial isoenzyme (sarcometric mitochondiral CK) accompanied by drug accumulation in mitochondria. Interestingly, DXR rapidly reduced the protein level and phosphorylation of AMPK as well as phosphorylation of its target, acetyl-CoA-carboxylase. AMPK was strongly affected already at 2 p,M DXR, even before substantial cardiac dysfunction occurred. Impairment of CK isoenzymes was mostly moderate but became significant at 20 p,M DXR. Only at 2 [micro]M DXR did upregulation of brain-type CK compensate for inactivation of other isoenzymes. These results suggest that an impairment of kinase systems regulating cellular energy homeostasis is involved in the development of DXR cardiotoxicity. creatine kinase; adenosine 5'-monophosphate-activated protein kinase; anthracyclines; cardiac energetics; cardiotoxicity

Published
2005

45. CompTIA Server+ : Serversysteme einrichten und betreiben.Vorbereitung auf die Prüfung SKO-005

Author

Roland Cattini, Markus Kammermann, Michael Zaugg, Roland Cattini, Markus Kammermann, and Michael Zaugg

Abstract

Praxiswissen für Administratoren zur Planung und Verwaltung von Serverumgebungen Fundierte Kenntnisse zur Problembehandlung und Fehlersuche für den Arbeitsalltag Mit praktischen Fragen und vielen Examenstipps Die Prüfung CompTIA Server+ richtet sich an IT-Fachleute und Administratoren und weist die Fähigkeiten nach, Server in Rechenzentren sowie in lokalen und hybriden Umgebungen zu installieren, zu verwalten und Fehler zu beheben. Die Zertifizierung ist nicht auf eine einzige Plattform beschränkt, so dass Sie die Aufgaben in jeder Umgebung ausführen können. Das Zertifikat ist international anerkannt. Die Prüfung SK0-005 teilt sich in diese Fachgebiete auf: Server-Hardware: Installation und Management Serveradministration Sicherheit und Disaster Recovery Fehlerbehebung Sie lernen in diesem Buch die Eigenschaften, den Einsatz und die Konfiguration von Servern von Grund auf kennen, sowohl was die Hardware als auch was die spezifischen Betriebs-systeme und Applikationen von Servern anbelangt. Des Weiteren erläutern die Autoren die Planung und die physischen Umgebungsbedingungen von Servern sowie aktuelle Themen wie z.B. Hochverfügbarkeit, Cloud Computing und Skripterstellung. Außerdem werden wichtige Fragen zur Sicherheit, Datensicherung und zum Disaster Recovery ausführlich behandelt. So können Sie sich das für die Zertifizierung benötigte Fachwissen aneignen und ein praxistaugliches Verständnis der Thematik entwickeln, das Sie in Ihrem Arbeitsalltag bei der Server-Administration voranbringt. Aus dem Inhalt: Server-Hardware: Prozessoren, Arbeitsspeicher, BIOS/UEFI Storage-Lösungen und -technologien: SSD, SAS, SATA, Fibre Channel, iSCSI Fehlertoleranz: RAID, Energieversorgung Server installieren und aktualisieren Hardware im Netzwerk: Kabel, Netzwerkkarten, Übertragungsgeräte TCP/IP: IPv4 und IPv6 Serverrollen: Datei- und Druckdienste, Internet- und Maildienste, Netzwerkdienste Netzwerkbetriebssysteme: Windows Server, UNIX/Linux und deren Installation Konfigurationsbetrachtungen: Dateisystem, Kontingentierung, Verzeichnisdienste, Gruppenrichtlinien Server Management: Remote-Verbindungen, Ereignisprotokolle, Monitoring Speichertechnologien, Virtualisierung und Cloud-Dienste Deployment- und Virtualisierungsszenarien Physische, technische und organisatorische Sicherheit Datensicherung in Theorie und Praxis Disaster Recovery Planning Unterhalt und Troubleshooting in der Praxis Die CompTIA Server+-Prüfung: Fragen, Antworten sowie ein Simulationstest in Englisch Roland Cattini ist Betriebs- und Elektroingenieur von Beruf und befasst sich seit Windows-NT-Zeiten als Microsoft-Experte mit Servern. Neben der Installation, Konfiguration und Wartung von Servern ist er in der Weiterbildung aktiv, nicht nur als MCSE und MCT, sondern auch als Netzwerk-Trainer und Dozent. Markus Kammermann, ausgebildeter ICT-Projektleiter und CompTIA Server+-Techniker, ist seit mehr als fünfundzwanzig Jahren in der System- und Netzwerktechnik tätig, fast ebenso lang als Ausbilder und Autor. Er engagiert sich zudem als Dozent in der höheren beruflichen Bildung. Michael Zaugg ist der UNIX- und Linux-Spezialist unter den drei Autoren. Er arbeitet als IT-Leiter und betreut mit seinem Team eine große Virtualisierungsumgebung auf Open-Source-Basis. In der Erwachsenenbildung ist er als Trainer zu Netzwerk- und Unix/Linux-Themen tätig.

Published
2022

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