Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase

Sergiy M. Nadtochiy, Qiuyu Zhu, William Urciuoli, Ruslan Rafikov, Stephen M. Black, Paul S. Brookes

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Electrophilic nitrated lipids (nitroalkenes) are emerging as an important class of protective cardiovascular signaling molecules. Although species such as nitro-linoleate (LNO 2) and nitro-oleate can confer acute protection against cardiac ischemic injury, their mechanism of action is unclear. Mild uncoupling of mitochondria is known to be cardioprotective, and adenine nucleotide translocase 1 (ANT1) is a key mediator of mitochondrial uncoupling. ANT1 also contains redox-sensitive cysteines that may be targets for modification by nitroalkenes. Therefore, in this study we tested the hypothesis that nitroalkenes directly modify ANT1 and that nitroalkene-mediated cardioprotection requires ANT1. Using biotin-tagged LNO 2 infused into intact perfused hearts, we obtained mass spectrometric (MALDI-TOF-TOF) evidence for direct modification (nitroalkylation) of ANT1 on cysteine 57. Furthermore, in a cell model of ischemia-reperfusion injury, siRNA knockdown of ANT1 inhibited the cardioprotective effect of LNO 2. Although the molecular mechanism linking ANT1-Cys 57 nitroalkylation and uncoupling is not yet known, these data suggest that ANT1-mediated uncoupling may be a mechanism for nitroalkene-induced cardioprotection.

Original languageEnglish (US)
Pages (from-to)3573-3580
Number of pages8
JournalJournal of Biological Chemistry
Volume287
Issue number5
DOIs
Publication statusPublished - Jan 27 2012

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nadtochiy, S. M., Zhu, Q., Urciuoli, W., Rafikov, R., Black, S. M., & Brookes, P. S. (2012). Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase. Journal of Biological Chemistry, 287(5), 3573-3580. https://doi.org/10.1074/jbc.M111.298406