title: Apolipoprotein A-I induces translocation of cholesterol, phospholipid, and caveolin-1 to cytosol in rat astrocytes.
abstract: Intercellular cholesterol transport in the brain is carried by high density lipoprotein (HDL) generated in situ by cellular interaction with the apolipoprotein apoE, which is mainly synthesized by astrocytes, and with apoA-I secreted by cells such as endothelial cells. Rat astrocytes in fact generate HDL with extracellular apoA-I in addition to releasing HDL with endogenously synthesized apoE, seemingly by the same mechanism as the HDL assembly for systemic circulation. Relating to this reaction, apoA-I induced translocation of newly synthesized cholesterol and phospholipid to the cytosol prior to extracellular assembly of HDL, accompanied by an increase of caveolin-1 in the cytosol, activation of sterol regulatory element-binding protein, and enhancement of cholesterol synthesis. The lipid translocated into the cytosol was recovered in the fraction with a density of 1.09-1.16 g/ml as well as caveolin-1 and cyclophilin A. Cyclosporin A inhibited these apoA-I-mediated reactions and suppressed apoA-I-mediated cholesterol release. The findings suggest that such translocation of cholesterol and phospholipid into the cytosol is related to the apo A-I-mediated HDL assembly in astrocytes through functional association with caveolin-1 and a cyclosporin A-sensitive cyclophilin protein(s).
authors.affiliation: Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Ito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagayasu
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008854:Microscopy, Electron; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D016632:Apolipoprotein A-I; C495540:CAV1 protein, human; C495537:Cav1 protein, rat; D051242:Caveolin 1; D022461:Caveolins; D003902:Detergents; D004791:Enzyme Inhibitors; D008075:Lipoproteins, HDL; D010743:Phospholipids; D016572:Cyclosporine; D002784:Cholesterol