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Quantitative redox proteomic analysis of reversible cysteine oxidation in hearts from mice fed a Western diet: implications for metabolic cardiovascular disease
Author(s) -
Behring Jessica B,
Kumar Vikas,
Siwik Deborah A,
Whelan Stephen A,
Colucci Wilson S,
Cohen Richard A,
McComb Mark E,
Bachschmid Markus M
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.558.3
Subject(s) - beta oxidation , oxidative stress , metabolic pathway , citric acid cycle , chemistry , oxidative phosphorylation , mitochondrion , biochemistry , cysteine , metabolism , medicine , endocrinology , biology , enzyme
Global changes in reversible cysteine oxidation of cardiac proteins from mice fed a high fat, high sucrose (HFHS) diet for 8 months were quantified using novel 6‐plex Iodo‐based isobaric labels in a switch assay and high resolution mass spectrometry. 400 reversibly oxidized proteins were identified, 56 with cysteines exhibiting more than 1.5‐fold change in oxidation by HFHS diet. As an improvement on “fold‐change”, our design also defined the percentage of oxidized cysteine at each site, or “site occupancy”. Nearly 50% of the proteins localized to mitochondria, consistent with this organelle being the primary target of metabolic stress resulting in mitochondrial oxidant formation. Multiple proteins in each of the critical metabolic pathways, including: the electron transport chain, tricarboxylic acid cycle, acyl‐carnitine shuttle, beta‐oxidation, and ketolysis, were reversibly oxidized. This suggests that substrate utilization pathways are dysfunctional. The condition further worsens as arterial stiffness increases energy demand of an overworked heart. All of these factors likely contribute to cardiac diastolic dysfunction and hypertrophy that occurs in the mice. Identifying and quantifying reversible oxidative protein changes will elucidate novel signaling mechanisms for switches in metabolism; these modifications could potentially serve as biomarkers for diet‐induced metabolic disease. NHLBI HHSN268201000031C