Apolipoprotein-mediated cellular lipid release requires replenishment of sphingomyelin in a phosphatidylcholine-specific phospholipase C-dependent manner.
When sphingomyelin is digested by sphingomyelinase in the plasma membrane of rat astrocytes, productions of sphingomyelin, diacylglycerol, and phosphatidylcholine are stimulated. D609, an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed these effects. Similarly, when apolipoprotein A-I removed cellular cholesterol, phosphatidylcholine, and sphingomyelin to generate high density lipoprotein, cholesterol synthesis from acetate subsequently increased, and sphingomyelin synthesis from acetate and serine also increased. D609 inhibited these effects again. D609 also inhibited the cholesterol removal by apoA-I not only from the astrocytes but also from BALB/3T3 and RAW264 cells. D609 decreased cholesterol synthesis, although D609 did not directly inhibit hydroxymethylglutaryl-CoA reductase. ApoA-I-stimulated translocation of newly synthesized cholesterol to cytosol was also decreased by D609. A diacylglycerol analog increased the apoA-I-mediated cholesterol release, whereas ceramide did not influence it. We concluded that removal of cellular sphingomyelin by apolipoproteins is replenished by transfer of phosphorylcholine from phosphatidylcholine to ceramide, and this reaction may limit the removal of cholesterol by apoA-I. This reaction also produces diacylglycerol that potentially triggers subsequent cellular signal cascades and regulates intracellular cholesterol trafficking.
Ito
Jin-ichi
J
Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi, 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Nagayasu
Yuko
Y
Ueno
Sachiko
S
Yokoyama
Shinji
S
D000085:Acetates / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D006801:Humans; D051379:Mice; D009636:Norbornanes; D010713:Phosphatidylcholines / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000085:Acetates; D016632:Apolipoprotein A-I; D001952:Bridged-Ring Compounds; D002518:Ceramides; D004075:Diglycerides; D009636:Norbornanes; D010713:Phosphatidylcholines; D010726:Phosphodiesterase Inhibitors; D013109:Sphingomyelins; D013859:Thiocarbamates; D013871:Thiones; C046498:tricyclodecane-9-yl-xanthogenate; D002784:Cholesterol; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; D013755:Tetradecanoylphorbol Acetate; D005990:Glycerol