CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver
CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver
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DOI：
10.1016/j.bbrc.2008.08.126
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发表时间：
2008-11-07
影响因子：
3.1
通讯作者：
Rozman, Damjana
中科院分区：
文献类型：
--
作者：
Acimovic, Jure;Fink, Martina;Rozman, Damjana
我们首次表明，cAMP反应元件调节剂Crem的亚型，调节Cyp 51和其他胆固醇基因在小鼠肝脏中的昼夜节律表达。在野生型小鼠中，Cyp 51、Hmgs、Fpps和Sqs的表达在CT 12和CT 16之间最小，在CT 20和CT 24之间达到峰值。Cyp 51、Fpps和Sqs在Crem-/-肝脏中失去了昼夜节律行为，而Hmgcr从CT 20提前到CT 12。这与通过GC-MS检测到的石杉甾醇/胆固醇比率的相位提前相一致。CREM tau和ICER的过表达对Hmgcr近端启动子几乎没有影响，而它们影响来自CYP 51启动子的表达。我们的数据表明，Crem依赖性调节Cyp 51在肝脏中的结果，在昼夜节律表达该基因。我们建议，cAMP信号转导可能通常参与了外周胆固醇合成的昼夜节律调节。(C)2008年爱思唯尔公司All rights reserved.
We show for the first time that isoforms of the cAMP response element modulator Crem, regulate the circadian expression of Cyp51 and other cholesterogenic genes in the mouse liver. In the wild type mice the expression of Cyp51, Hmgs, Fpps, and Sqs is minimal between CT12 and CT16 and peaks between CT20 and CT24. Cyp51, Fpps, and Sqs lost the circadian behavior in Crem-/- livers while Hmgcr is phase advanced from CT20 to CT12. This coincides with a phase advance of lathosterol/cholesterol ratio, as detected by GC-MS. Overexpression of CREM tau and ICER has little effect on the Hmgcr proximal promoter while they influence expression from the CYP51 promoter. Our data indicate that Crem-dependent regulation of Cyp51 in the liver results in circadian expression of this gene. We propose that cAMP signaling might generally be involved in the circadian regulation of cholesterol synthesis on the periphery. (C) 2008 Elsevier Inc. All rights reserved.