Abstract
Helical apolipoproteins interact with cellular surface and generate high density lipoprotein (HDL) by removing phospholipid and cholesterol from cells. We have reported that the HDL is generated by this reaction with the fetal rat astrocytes and meningeal fibroblasts but cholesterol is poorly available to this reaction with the astrocytes (Ito et al. 1999. J. Neurochem. 72: 2362–2369). Partial digestion of the membrane by extracellular sphingomyelinase increased the incorporation of cholesterol into thus-generated HDL from both types of cell. This increase was diminished by supplement of endogenous or exogenous sphingomyelin to the cells. The sphingomyelinase treatment decreased cholesterol in the membrane mainly in the detergent-resisting domain. The intracellular cholesterol used by acylCoA:cholesterol acyltransferase increased by the sphingomyelinase treatment in the absence of apoA-I, more remarkably in the fibroblast than in the astrocytes. ApoA-I suppressed this increase completely in the astrocytes, but only partially in the fibroblast. The effect of the sphingomyelin digestion was more prominent for the apolipoprotein-mediated reaction than the diffusion-mediated cellular cholesterol efflux.Thus, cholesterol molecules restricted by sphingomyelin in the domain of the plasma membrane appear to be primarily used for the HDL assembly upon the apolipoprotein–cell interaction.—Ito, J., Y. Nagayasu, and S. Yokoyama. Cholesterol–sphingomyelin interaction in membrane and apolipoprotein-mediated cellular cholesterol efflux. J. Lipid Res. 2000. 41: 894–904.
Highlights
Helical apolipoproteins interact with cellular surface and generate high density lipoprotein (HDL) by removing phospholipid and cholesterol from cells
We studied the effect of the digestion of the cellular sphingomyelin on the apolipoprotein-mediated HDL assembly, focusing the cholesterol incorporation into the HDL. We demonstrated that this treatment lead to the increase of cholesterol in the HDL generated with extracellular apolipoprotein
1) The treatment of the cells with SMase enhanced the apolipoprotein-mediated cholesterol release from the cell in a manner of increasing cholesterol incorporation into the HDL to generate cholesterol-richer HDL. 2) This effect was related to the decrease of cellular sphingomyelin, and supplementation with sphingomyelin endogenous or exogenous reversed the effect of the digestion
Summary
Helical apolipoproteins interact with cellular surface and generate high density lipoprotein (HDL) by removing phospholipid and cholesterol from cells. Apolipoprotein–cell interaction and subsequent generation of high density lipoprotein (HDL) from the cellular lipid [1] constitute one of the major pathways for the release of cellular cholesterol, an important component of the cellular and body sterol homeostasis [2] This reaction requires several cellular elements including an apolipoprotein interaction site on cell surface [3], assembly of HDL by apolipoprotein with membrane phospholipid [4], signaling to initiate intracellular cholesterol mobilization and specific intracellular cholesterol trafficking for the assembly of the HDL [5]. The intracellular cholesterol pool available for the acylCoA:cholesterol acyltransferase (ACAT) mildly but rapidly decreased in response to apoA-I indicating that the intracellular cholesterol mobilization system for the apolipoprotein-mediated HDL generation itself is active By using this model, we intended to investigate the local environment of cholesterol molecules in the plasma membrane that may regulate cholesterol availability for the HDL assembly by apolipoproteins.
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