Biochemical and Biophysical Research Communications
CREM modulates the circadian expression of CYP51, HMGCR and cholesterogenesis in the liver
Section snippets
Materials and methods
Animals. The Crem−/− animals originate from the laboratory of Dr. P. Sassone-Corsi, IGBMC, Strasbourg, France. The protocols for animal care followed the EU regulations. Male mice (13–24 weeks old) were for 7 days under 12 h light and 12 h dark condition, followed by a 24 h dark cycle before being sacrificed. Sacrification took place in the dark, under red light. Blood was collected into EDTA-coated tubes, centrifuged (plasma), livers cut into pieces and immediately frozen in liquid N2. Samples
CREM/ICER influence the expression of cholesterogenic genes
RT-PCR analyses of cholerestogenic Hmgs, Fpps, Sqs, Cyp51, Srebp-2, and Hmgcr from w.t. and Crem−/− mouse liver tissue are shown in Fig 1. In wild type animals (grey lines), the one-way ANOVA (p < 0.05) of Hmgcr expression (Fig. 1B) showed maximal expression in the dark phase at CT20 which is in accordance by previous works [17] and is consistent with the HMGCR activity [18]. The expression of other genes of cholesterol synthesis (Hmgs, Fpps, Sqs, Cyp51) is minimal between CT12 and CT16 (start of
Discussion
Liver is a central organ of the bodies homeostasis and has a unique ability to regenerate. Liver is also a circadian organ where many metabolic processes exhibit a rhythmic regulation. Increased cAMP levels and the cAMP regulatory element modulator isoforms CREM and ICER were so far shown to be involved in the hepatic regeneration and proliferation [22], ICER was overexpressed in the hepatocellular carcinoma, [23] and was induced after the forskolin treatment in immortal cell lines, including
Acknowledgments
The work was supported by the Slovenian Research Agency, Grants J1-6713, J1-9428 and P1-0104. Thanks also to FEBS (Federation of European Biochemical Societies) for fellowship grant to Jure Acimovic and to EMBO (European Molecular Biology Organization) for the fellowship to D. Rozman. Part of the work has been generated in the context of the STEROLTALK project, funded by the European Community as contract No. LSHG-CT-2005-512096 under 6th Framework Programme for Research and Technological
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2011, Biochemical and Biophysical Research CommunicationsCitation Excerpt :These include lanosterol-14α-demethylase (CYP51), which is regulated by negative feedback through sterol regulatory-element-binding proteins (SREBPs) and also by cAMP-dependent transcription factors [13,14]. It was reported previously that cAMP response element modulator (CREM) and the inducible cAMP early repressor (ICER) are involved in the circadian expression of Cyp51 and other cholesterogenic genes in mouse liver [15,16], although they are better known for their roles in the neuroendocrine system [17]. However, the molecular mechanisms and physiological roles of cAMP signalling in hepatic cholesterol synthesis remain poorly understood.