Role of fatty acid beta-oxidation and calcium-independent phospholipase A₂ in ischemic acute renal failure

Abstract

Membrane phospholipolysis during ischemic cell injury is accompanied by the activation of a novel calcium-independent phospholipase A₂ in the proximal tubule. Long-chain fatty acid metabolic products produced by phospholipase A₂ activation accumulate during ischemia as a result of the inhibition of fatty acid β-oxidation on the mitochondria and peroxisomes. Altogether, lysophospholipids, long-chain acyl carnitines, and long-chain acyl coenzyme A inhibit proximal tubule Na⁺K⁺-ATPase. Metabolic regulation of the gene expression of fatty acid β-oxidation enzymes during ischemic acute renal failure may represent a novel therapeutic maneuver to enhance the recovery of kidney function during ischemia.