文章基本信息

标题：Unsaturated fatty acids phosphorylate and destabilize ABCA1 through a protein kinase C {delta} pathway
本地全文：下载
作者：Wang, Yutong ; Oram, John F.
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2007
卷号：48
期号：5
页码：1062-1068
DOI：10.1194/jlr.M600437-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Abnormal HDL metabolism among patients with diabetes and insulinresistance may contribute to their increased risk of atherosclerosis.ABCA1 mediates the transport of cholesterol and phospholipidsfrom cells to HDL apolipoproteins and thus modulates HDL levelsand atherogenesis. Unsaturated fatty acids, which are increasedin diabetes, impair the ABCA1 pathway in cultured cells by destabilizingABCA1 protein. We previously reported that unsaturated fattyacids destabilize ABCA1 in murine macrophages and ABCA1-transfectedbaby hamster kidney cells by increasing its serine phosphorylationthrough a phospholipase D (PLD) pathway. Here, we examined thecellular pathway downstream of PLD that mediates the ABCA1-destabilizingeffects of unsaturated fatty acids. The protein kinase C ${delta}$ (PKC ${delta}$ )-specificinhibitor rottlerin and PKC ${delta}$ small interfering RNA completelyabolished the ability of unsaturated fatty acids to inhibitlipid transport activity, to reduce protein levels, and to increaseserine phosphorylation of ABCA1, implicating a role for PKC ${delta}$ in the ABCA1-destabilizing effects of fatty acids. These dataindicate that unsaturated fatty acids destabilize ABCA1 by activatinga PKC ${delta}$ pathway that phosphorylates ABCA1 serines. Supplementary key words ATP binding cassette transporter A1 • high density lipoproteins • cardiovascular disease • diabetes