Induction of choline kinase alpha by carbon tetrachloride (CCl₄) occurs via increased binding of c-jun to an AP-1 element

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• 作者：Chieko Aoyama ; Kozo Ishidate ; Hiroyuki Sugimoto ; Dennis E. Vance
• 关键词：Choline kinase ; Alpha carbon tetrachloride ; AP-1 element
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2007
• 出版时间：September 2007
• 年：2007
• 卷：1771
• 期：9
• 页码：1148-1155
• 全文大小：969 K

文摘

The mechanism by which treatment of mice with CCl₄ induces an increase in choline kinase α has been investigated. Nuclear run on assays demonstrated a major increase in the transcript for choline kinase α in livers from mice 3 h and 6 h after administration of CCl₄ compared to vehicle (olive oil). 5′deletion analyses of choline kinase α promoter-luciferase constructs expressed in Hepa-1 cells identified a promoter element between − 875 and − 866 that was nearly identical to an AP-1 consensus site. Mutation of this AP-1 site caused a striking decrease in the expression of choline kinase α promoter-luciferase constructs. Electromobility shift assays with nuclear extracts from mouse liver demonstrated that c-Jun, but not c-fos, bound oligonucleotides with the AP-1 site. The amount of c-jun bound was greatly increased when hepatic nuclear extracts from mice treated with CCl₄ were used. Chromatin immunoprecipitation assays confirmed that c-jun binds to the choline kinase α promoter. The results from these studies provide strong evidence that the choline kinase α promoter has a distal element (− 875/− 867) that binds c-jun and the binding of c-jun is enhanced by treatment with CCl₄.