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Does reversible cysteine oxidation link the Western diet to cardiac dysfunction?

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TitleDoes reversible cysteine oxidation link the Western diet to cardiac dysfunction?
Publication TypeJournal Article
Year of Publication2014
AuthorsBehring JB, Kumar V, Whelan SA, Chauhan P, Siwik DA, Costello CE, Colucci WS, Cohen RA, McComb ME, Bachschmid MM
JournalFASEB J
Volume28
Issue5
Pagination1975-87
Date Published2014 May
ISSN1530-6860
KeywordsAnimals, Chromatography, Liquid, Citric Acid Cycle, Cysteine, Diet, Fatty Acids, Glycolysis, Heart Diseases, Male, Mice, Mice, Inbred C57BL, Myocardial Contraction, Myocardium, Obesity, Oxidative Phosphorylation, Oxygen, Phenotype, Protein Processing, Post-Translational, Proteomics, Reactive Nitrogen Species, Reactive Oxygen Species, Sulfhydryl Compounds, Tandem Mass Spectrometry
Abstract

Using a novel cysteine thiol labeling strategy coupled with mass spectrometric analysis, we identified and quantified the changes in global reversible cysteine oxidation of proteins in the left ventricle of hearts from mice with metabolic syndrome-associated diastolic dysfunction. This phenotype was induced by feeding a high-fat, high-sucrose, type-2 diabetogenic diet to C57BL/6J mice for 8 mo. The extent of reversible thiol oxidation in relationship to the total available (free and reducible) level of each cysteine could be confidently determined for 173 proteins, of which 98 contained cysteines differentially modified ≥1.5-fold by the diet. Our findings suggest that the metabolic syndrome leads to potentially deleterious changes in the oxidative modification of metabolically active proteins. These alterations may adversely regulate energy substrate flux through glycolysis, β-oxidation, citric acid (TCA) cycle, and oxidative phosphorylation (oxphos), thereby contributing to maladaptive tissue remodeling that is associated with, and possibly contributing to, diastolic left ventricular dysfunction.

DOI10.1096/fj.13-233445
Alternate JournalFASEB J.
PubMed ID24469991
PubMed Central IDPMC4046179
Grant ListN01 HV028178 / HV / NHLBI NIH HHS / United States
HL-064750 / HL / NHLBI NIH HHS / United States
R01 HL064750 / HL / NHLBI NIH HHS / United States
HHSN268201000031C / HL / NHLBI NIH HHS / United States
P01-HL-068758 / HL / NHLBI NIH HHS / United States
R01 HL031607 / HL / NHLBI NIH HHS / United States
HL-31607 / HL / NHLBI NIH HHS / United States
HHSN268201000031C / / PHS HHS / United States
P01 HL068758 / HL / NHLBI NIH HHS / United States
R37-HL-104017 / HL / NHLBI NIH HHS / United States
T32 HL007501 / HL / NHLBI NIH HHS / United States
P41 GM104603 / GM / NIGMS NIH HHS / United States
R37 HL104017 / HL / NHLBI NIH HHS / United States