Atherogenic diet leads to posttranslational down-regulation of murine hepatocyte SR-BI expression

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• 作者：Andreas Niemeier ; Werner J. Kovacs ; Wolfgang Strobl ; Herbert Stangl
• 关键词：SR-BI ; PDZK1 ; Cholesterol ; Mouse ; SREBP ; Liver ; Posttranslational regulation
• 刊名：Atherosclerosis
• 出版年：2009
• 出版时间：January 2009
• 年：2009
• 卷：202
• 期：1
• 页码：169-175
• 全文大小：1300 K

文摘

The scavenger receptor class B, type I (SR-BI) mediates selective cholesteryl ester uptake by the liver and thereby exerts a systemic anti-atherogenic effect. It is unknown, however, whether exogenous cholesterol contributes to the regulation of hepatic SR-BI expression. Atherosclerosis resistant SJL and susceptible C57Bl/6 mice were challenged with atherogenic diets that lead to an increase of both plasma and liver cholesterol. The increase of cholesterol was accompanied by a marked posttranslational down-regulation of liver SR-BI expression. On average, we observed a threefold decrease of SR-BI protein while mRNA levels were slightly increased in both strains. Mice with transgenic over-expression of the sterol regulatory element binding proteins (SREBPs) were used as a model that displays endogenously increased liver cholesterol concentrations. In SREBP-1a and -1c transgenic mice on normal chow, SR-BI was transcriptionally down-regulated. When fed the atherogenic diet, the posttranslational SR-BI regulation was still functional on this background. Down-regulation of SR-BI did not alter the hepatocyte surface expression pattern, but was accompanied by a decrease of PDZK1, an adaptor protein recently identified to control SR-BI protein expression levels in the liver and intestine. Taken together, a diet-induced increase of plasma and hepatic cholesterol levels leads to a posttranscriptional down-regulation of SR-BI in mouse liver via a mechanism likely involving PDZK1.