RRC ID 1290
著者 Wu CA, Tsujita M, Hayashi M, Yokoyama S.
タイトル Probucol inactivates ABCA1 in the plasma membrane with respect to its mediation of apolipoprotein binding and high density lipoprotein assembly and to its proteolytic degradation.
ジャーナル J Biol Chem
Abstract Probucol has been shown to inhibit the release of cellular lipid by helical apolipoprotein and thereby to reduce plasma high density lipoprotein. We attempted to explore the underlying mechanism for this effect in human fibroblast WI-38. Probucol inhibited the apoA-I-mediated cellular lipid release and binding of apoA-I to the cells in a dose-dependent manner. It did not influence cellular uptake of low density lipoprotein, transport of cholesterol to the cell surface whether de novo synthesized or delivered as low density lipoprotein, and overall cellular content of cholesterol, although biosynthesis of lipids from acetate was somewhat increased. Probucol did not affect the mRNA level of ABCA1, and ABCA1 was recovered along with marker proteins for plasma membrane regardless of the presence of probucol. However, the protein level of ABCA1 increased, and the rate of its decay in the presence of cycloheximide was slower in the probucol-treated cells. ABCA1 in the probucol-treated cells was resistant to digestion by calpain but not by trypsin. We concluded that probucol inactivates ABCA1 in the plasma membrane with respect to its function in mediating binding of and lipid release by apolipoprotein and with respect to proteolytic degradation by calpain.
巻・号 279(29)
ページ 30168-74
公開日 2004-7-16
DOI 10.1074/jbc.M403765200
PII S0021-9258(19)71029-1
PMID 15140889
MeSH ATP Binding Cassette Transporter 1 ATP-Binding Cassette Transporters / chemistry ATP-Binding Cassette Transporters / metabolism* Anticholesteremic Agents / pharmacology* Apolipoproteins / metabolism* Blotting, Western Calpain / metabolism Cell Membrane / metabolism* Cholesterol / metabolism Cholesterol Oxidase / metabolism Dose-Response Relationship, Drug Fibroblasts / metabolism Humans Lipid Metabolism Lipoproteins, HDL / metabolism Lipoproteins, LDL / metabolism Probucol / pharmacology* Protein Binding RNA / metabolism RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Subcellular Fractions / metabolism Time Factors Transcription, Genetic Trypsin / pharmacology
IF 4.238
引用数 75
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 WI-38