| Autor: |
Kinsey, Gilbert R., McHowat, Jane, Beckett, Caroline S., Schnellman, Rick G. |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Renal Physiology; Feb2007, Vol. 292, pF853-F860, 8p, 1 Diagram, 6 Graphs |
| Abstrakt: |
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 iPLA2γ is the RCM iPLA2 activity. RCM iPLA2 activity was enhanced in the presence of ATP and was blocked by the PKCϵ 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 iPLA2γ activity. These results reveal that RCM iPLA2 is iPLA2γ, RCM iPLA2γ is regulated by phosphorylation by PKCϵ, iPLA2γ protects RCM from oxidant-induced lipid peroxidation and dysfunction, and that a strategy to preserve or enhance iPLA2γ activity may be of therapeutic benefit. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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