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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/F853    most recent 00318.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Kinsey, G. R. Articles by Schnellmann, R. G. Search for Related Content PubMed PubMed Citation Articles by Kinsey, G. R. Articles by Schnellmann, R. G.

Identification of calcium-independent phospholipase A₂ in mitochondria and its role in mitochondrial oxidative stress

¹Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina; and ²Department of Pathology, St. Louis University, St. Louis, Missouri

Submitted 11 August 2006 ; accepted in final form 6 October 2006

Oxidant-induced lipid peroxidation and cell death mediate pathologies associated with ischemia-reperfusion and inflammation. Our previous work in rabbit renal proximal tubular cells (RPTC) demonstrated that inhibition of Ca²⁺-independent phospholipase A₂ (iPLA₂) potentiates oxidant-induced lipid peroxidation and necrosis, implicating iPLA₂ in phospholipid repair. This study was conducted to identify a RPTC mitochondrial PLA₂ and determine the role of PLA₂ in oxidant-induced mitochondrial dysfunction. iPLA₂ activity was detected in Percoll-purified rabbit renal cortex mitochondria (RCM) and in isolated mitochondrial inner membrane fractions from rabbit and human RCM. Immunoblot analysis and inhibitor sensitivity profiles revealed that iPLA₂ is the RCM iPLA₂ activity. RCM iPLA₂ activity was enhanced in the presence of ATP and was blocked by the PKC V1–2 inhibitor. Oxidant-induced mitochondrial lipid peroxidation and swelling were accelerated by pretreatment with R-BEL, but not S-BEL. Furthermore, oxidant treatment of isolated RCM resulted in decreased iPLA₂ activity. These results reveal that RCM iPLA₂ is iPLA₂, RCM iPLA₂ is regulated by phosphorylation by PKC, iPLA₂ protects RCM from oxidant-induced lipid peroxidation and dysfunction, and that a strategy to preserve or enhance iPLA₂ activity may be of therapeutic benefit.

group VIB PLA₂; lipid peroxidation

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