Effects of sphingomyelin on apolipoprotein E- and lipoprotein lipase-mediated cell uptake of lipid particles.
It has been reported that human plasma sphingomyelin (SM) levels are positively and independently related to coronary artery disease. The lipoprotein surface is mainly formed by phosphatidylcholine (PC) and SM together with cholesterol and apolipoproteins. However, the influence of SM on the cell uptake of triglyceride-rich lipoproteins and remnants is poorly understood. To clarify the role of SM in lipoprotein uptake, we prepared lipid emulsions containing triolein, PC and SM as model particles of lipoproteins. Apolipoprotein E (ApoE) binding studies revealed that incorporation of SM into the emulsion surface reduced the binding capacity of apoE without changing the affinity. Surface SM reduced apoE-mediated uptake of emulsions by HepG2 cells because of the decreased amount of binding apoE. Apolipoproteins C-II and C-III inhibited the apoE-mediated uptake of SM containing emulsions more effectively. The stimulatory effect of lipoprotein lipase (LPL) on emulsion uptake was decreased by replacing surface PC with SM. These results suggest that SM-induced changes in the binding properties of apolipoproteins and LPL correlate with decreased hepatic uptake of lipid particles.
Morita
Shin-ya
SY
Graduate School of Pharmaceutical Science, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Okuhira
Keiichirou
K
Tsuchimoto
Nanoko
N
Vertut-Doï
Aline
A
Saito
Hiroyuki
H
Nakano
Minoru
M
Handa
Tetsurou
T
D001056:Apolipoproteins C / Q000378:metabolism / Q000494:pharmacology; D001057:Apolipoproteins E / Q000378:metabolism*; D004655:Emulsions / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D013109:Sphingomyelins / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D001056:Apolipoproteins C; D001057:Apolipoproteins E; D004655:Emulsions; D013109:Sphingomyelins; D008071:Lipoprotein Lipase