A pH-dependent phospholipase A2 contributes to loss of plasma membrane integrity during chemical hypoxia in rat hepatocytes.
Previous studies have suggested that alterations in phospholipid composition of plasma membranes may underlie lethal cell injury due to hypoxic and ischemic injury. The present study was designed to determine if such alterations are due to the activation of a pH-dependent phospholipase A2. Loss of cell viability and phospholipase A2 activity measured by arachidonic acid release increased in parallel during metabolic inhibition with KCN and iodoacetate (chemical hypoxia). Acidosis (pH 6.5) and the phospholipase inhibitors, dibucaine and mepacrine, delayed loss of cell viability and release of arachidonic acid to a similar extent. These findings suggest that a pH-dependent phospholipase A2 causes alterations in plasma membrane phospholipid composition after ATP-depletion which contribute to lethal cell injury.
Harrison
D C
DC
Department of Cell Biology & Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Lemasters
J J
JJ
Herman
B
B
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002462:Cell Membrane / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007461:Iodoacetates / Q000494:pharmacology*; D019807:Iodoacetic Acid; D007700:Kinetics; D008297:Male; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011190:Potassium Cyanide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001095:Arachidonic Acids; D007461:Iodoacetates; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D011190:Potassium Cyanide; D019807:Iodoacetic Acid