Hepatic lipase stimulates the uptake of high density lipoprotein cholesterol by hepatoma cells.
The objective of this study was to determine whether high density lipoproteins (HDL) that have been treated with hepatic lipase have an enhanced ability to deliver cholesterol to cells. Human HDL was incubated with rat hepatic lipase, reisolated, and subjected to compositional analysis. Approximately 28% of the HDL phosphatidylcholine was hydrolyzed by the hepatic lipase but no change was detected in the cholesterol or apoprotein content of the HDL compared to HDL incubated with heat-inactivated hepatic lipase. Cultured rat hepatoma cells exposed to hepatic lipase-modified HDL showed an increased uptake of HDL free cholesterol relative to cells exposed to control HDL. This increased delivery of HDL free cholesterol was demonstrated by both isotopic and mass determinations and it contributed to a 1.6-fold increase in total cellular cholesterol content relative to cells treated with control HDL. The free cholesterol delivered by the HDL is functionally available to the cell as evidenced by the conversion of radiolabeled free cholesterol to cholesteryl ester. The stimulation of free cholesterol delivery was dose-dependent up to a level of 100 micrograms of HDL free cholesterol/ml of extracellular medium, and was directly related to the extent of phosphatidylcholine hydrolysis. The enhanced cellular accumulation of HDL free cholesterol observed with hepatic lipase appears to be due to the phospholipase activity of this enzyme, since similar results were obtained with HDL that had been modified by snake venom phospholipase A2.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL; D008049:Lipase / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D051381:Rats
D001053:Apolipoproteins; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002784:Cholesterol; D008049:Lipase