出版社：American Society for Biochemistry and Molecular Biology
摘要：Although sphingomyelin (SM) is a major phospholipid in lipoproteinsas well as in the membrane rafts where the scavenger receptorclass B type I (SR-BI) is localized, its possible role in theselective uptake of cholesteryl ester (CE) by the SR-BI-mediatedpathway is unknown. We investigated the effect of SM in lipoproteinsand cell membranes on the selective uptake in three differentcell lines: SR-BI-transfected CHO cells, hepatocytes (HepG2),and adrenocortical cells (Y1BS1). Incorporation of SM into recombinanthigh density lipoprotein (rHDL) containing labeled CE resultedin up to 50% inhibition of the selective uptake of CE in allthree cell lines. This inhibition was completely reversed bytreatment of rHDL with sphingomyelinase (SMase). Selective uptakefrom plasma HDL was activated by 22–72% after treatmentof HDL with SMase. In addition, pretreatment of the cells withSMase resulted in stimulation of CE uptake from rHDL by CHOand Y1BS1, although not by HepG2. Incorporation of ceramideinto rHDL resulted in up to 2-fold stimulation of CE uptake,although pretreatment of cells with egg ceramide had no significanteffect.
These results show that SM and ceramide in the lipoproteinsand the cell membranes regulate the SR-BI-mediated selectiveuptake of CE, possibly by interacting with the sterol ring orwith SR-BI itself.Abbreviations: ACTH, adrenocorticotropic hormone; apoA-I, apolipoprotein A-I; CE, cholesteryl ester; FC, free cholesterol; PC, phosphatidylcholine; rHDL, recombinant high density lipoprotein; SM, sphingomyelin; SMase, sphingomyelinase; SR-BI, scavenger receptor class B type I
Supplementary key words scavenger receptor class B type I • ceramide • sphimgomyelinase • hepatocytes • adrenocortical cells
