Role of Phospholipase A<SUB>2</SUB> in Hypoxia-Induced Renal Cell Injury

Role of Phospholipase A<SUB>2</SUB> in Hypoxia-Induced Renal Cell Injury

<P> The present study was designed to assess the roles of PLA<SUB>2</SUB> activation and arachidonic acid (AA) metabolites in hypoxia-induced renal cell injury. Hypoxia increased LDH release in a dose-dependent manner in rabbit renal cortical slices, and this increase was significant after 20-min hypoxia. The hypoxia-induced LDH release was prevented by amino acids, glycine and alanine, and extracellular acidosis (pH 6.0). Buffering intracellular Ca<SUP>2&#8290;</SUP> by a chelator, but not omission of Ca<SUP>2&#8290;</SUP> in the medium produced a significant reduction in hypoxia-induced LDH release. The effect of hypoxia was blocked by PLA<SUB>2</SUB> inhibitors, mepacrine, butacaine, and dibucaine. A similar effect was observed by a 85-kD cPLA<SUB>2</SUB> inhibitor AACOCF<SUB>3</SUB>. AA increased hypoxia-induced LDH release, and albumin, a fatty acid absorbent, prevented the LDH release, suggesting that free fatty acids are involved in hypoxia-induced cell injury. These results suggest that PLA<SUB>2</SUB> activation and its metabolic products play important roles in pathogenesis of hypoxia-induced cell injury in rabbit renal cortical slices.