Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II

Jeffrey R. Koenitzer, Gustavo Bonacci, Steven R. Woodcock, Chen Shan Chen, Nadiezhda Cantu-Medellin, Eric E. Kelley, Francisco J. Schopfer

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Nitro-fatty acids (NO2-FA) are metabolic and inflammatory-derived electrophiles that mediate pleiotropic signaling actions. It was hypothesized that NO2-FA would impact mitochondrial redox reactions to induce tissue-protective metabolic shifts in cells. Nitro-oleic acid (OA-NO2) reversibly inhibited complex II-linked respiration in isolated rat heart mitochondria in a pH-dependent manner and suppressed superoxide formation. Nitroalkylation of Fp subunit was determined by BME capture and the site of modification by OA-NO2 defined by mass spectrometric analysis. These effects translated into reduced basal and maximal respiration and favored glycolytic metabolism in H9C2 cardiomyoblasts as assessed by extracellular H+ and O2 flux analysis. The perfusion of NO2-FA induced acute cardioprotection in an isolated perfused heart ischemia/reperfusion (IR) model as evidenced by significantly higher rate-pressure products. Together these findings indicate that NO2-FA can promote cardioprotection by inducing a shift from respiration to glycolysis and suppressing reactive species formation in the post-ischemic interval.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalRedox Biology
Volume8
DOIs
StatePublished - Aug 1 2016

Keywords

  • Electrophile
  • Inflammation
  • Mitochondria
  • Nitro-fatty acid
  • Nitroalkene

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