Role of Phospholipase $A_2$ in Hypoxia-Induced Renal Cell Injury

  • Choi, Won-Rak (Department of Physiology, College of Medicine, Pusan National University) ;
  • Ko, Sun-Hee (Department of Physiology, College of Medicine, Pusan National University) ;
  • Cho, Su-In (Department of Physiology, College of Medicine, Pusan National University) ;
  • Woo, Jae-Suk (Department of Physiology, College of Medicine, Pusan National University) ;
  • Jung, Jin-Sup (Department of Physiology, College of Medicine, Pusan National University) ;
  • Lee, Sang-Ho (Department of Physiology, College of Medicine, Pusan National University) ;
  • Kim, Yong-Keun (Department of Physiology, College of Medicine, Pusan National University)
  • Published : 1999.02.21

Abstract

The present study was designed to assess the roles of $PLA_2$ 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 $Ca^{2+}$ by a chelator, but not omission of $Ca^{2+}$ in the medium produced a significant reduction in hypoxia-induced LDH release. The effect of hypoxia was blocked by $PLA_2$ inhibitors, mepacrine, butacaine, and dibucaine. A similar effect was observed by a 85-kD $cPLA_2$ inhibitor $AACOCF_3.$ 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 $PLA_2$ activation and its metabolic products play important roles in pathogenesis of hypoxia-induced cell injury in rabbit renal cortical slices.