| Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1. | |
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MedLine Citation:
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PMID: 22158628 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 (OANO(2)) 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 IR injury, siRNA knock-down of ANT1 inhibited the cardioprotective effect of LNO(2). Although the molecular mechanism linking ANT1-C(57) nitroalkylation and uncoupling is not yet known, these data suggest that ANT1 mediated uncoupling may be a mechanism for nitroalkene induced cardioprotection. |
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Authors:
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Sergiy M Nadtochiy; Qiuyu Zhu; William Urciuoli; Ruslan Rafikov; Steven M Black; Paul S Brookes |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-9 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Rochester Medical Center, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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