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Identification of oxidized and S‐nitrosylated mitochondrial proteins in hepatic ischemia‐reperfusion injury

Hepatic ischemia‐reperfusion (I/R) injury is a pathophysiological process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery to the compromised tissue. Despite numerous reports on the role of oxidative stress and mitochondrial dysfunction in hepatic I/R in...

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Bibliographic Details
Published in:The FASEB journal 2007-04, Vol.21 (5), p.A662-A662
Main Authors: Moon, Kwan‐Hoon, Hood, Brian L., Mukhopadhyay, Partha, Conrads, Thomas P., Veenstra, Timothy D., Song, Byoung J., Pacher, Pal
Format: Article
Language:English
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Summary:Hepatic ischemia‐reperfusion (I/R) injury is a pathophysiological process whereby hypoxic organ damage is accentuated following return of blood flow and oxygen delivery to the compromised tissue. Despite numerous reports on the role of oxidative stress and mitochondrial dysfunction in hepatic I/R injury, the proteins that are oxidized during reperfusion damage are poorly characterized. We hypothesized that certain Cys residues of mitochondrial proteins are oxidized and S‐nitrosylated by hepatic I/R. To test this hypothesis, the oxidized and/or S‐nitrosylated mitochondrial proteins in mouse livers subjected to I/R with or without a peroxynitrite scavenger pre‐treatment, were labeled with biotin‐NM as a probe, purified with streptavidin‐agarose and resolved on 2‐DE. We compared the patterns of oxidatively‐modified mitochondrial proteins with and without the peroxynitrite scavenger to study the beneficial effect of the neutralization of peroxynitrite on oxidative inactivation of the key mitochondrial proteins. We observed markedly increased levels of oxidized and S‐nitrosylated mitochondrial proteins following hepatic I/R injury. Addition of the peroxynitrite scavenger selectively prevented S‐nitrosylation of proteins. Decreased levels of S‐nitrosylated proteins were associated with significantly reduced levels of hepatic injury following I/R determined by histological examination and serum transaminase activities. Our results thus explain the underlying mechanisms for the mitochondrial dysfunction in hepatic I/R injury.
ISSN:0892-6638
1530-6860
DOI:10.1096/fasebj.21.5.A662-a