Hydrolysis of sarcolemma by lysosomal lipases and inhibition by chlorpromazine.
The susceptibility of the lipids of canine cardiac sarcolemma to attack by soluble lysosomal lipases was studied to simulate in vitro the lipolytic injury that occurs during ischemia. The sarcolemmal fraction was incubated at 37 degrees C with the soluble portion of rat hepatic lysosomes (the lysosol) under conditions (pH 5.0, 5 mM ethylenediaminetetraacetic acid) appropriate for the activity of the major lysosomal lipases. Incubation of sarcolemma with lysosol resulted in a 78% lipolysis of sarcolemmal triacylglycerols, a lesser degradation of glycerophospholipids, and a parallel production of free fatty acids and lysophospholipids. The hydrolysis of sphingomyelin was negligible but was greatly stimulated (75%) by the addition of Triton X-100 (1 mg). Endogenous lipolytic activities of the sarcolemma did not contribute significantly to the observed lipid hydrolysis either in the presence or absence of detergent. The lipolysis of sarcolemmal triacylglycerols, glycerophospholipids, and sphingomyelin (Triton X-100 stimulated) were inhibited by varying concentrations of chlorpromazine. Thus cardiac sarcolemma is susceptible to hydrolysis of lysosomal lipases, and chlorpromazine inhibits this potentially injurious process.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D004285:Dogs; D005227:Fatty Acids / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D008049:Lipase / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D012508:Sarcolemma / Q000502:physiology*
D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D008049:Lipase; D002746:Chlorpromazine