Docosahexaenoic acid downregulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes via the c-Jun NH2-terminal kinase mitogen-activated protein kinase pathway

doi:10.1016/j.jnutbio.2009.01.007

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 營養學系暨碩士班 > 期刊論文 > Item 310902500/3804

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題名:	Docosahexaenoic acid downregulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes via the c-Jun NH2-terminal kinase mitogen-activated protein kinase pathway
作者:	Chia-Yang Lu;Chien-Chun Li;Kai-Li Liu;Chong-Kuei Lii;Haw-Wen Chen
貢獻者:	中山醫學大學:營養系
關鍵詞:	Affiliations;CYP 2B1;DHA;Hepatocytes;Mitogen-activated protein kinases;PUFA
日期:	2009
上傳時間:	2011-05-23T07:27:16Z (UTC)
ISSN:	0955-2863
摘要:	Mitogen-activated protein kinase (MAPK) pathways play central roles in the transduction of extracellular stimuli into cells and the regulation of expression of numerous genes. Docosahexaenoic acid (DHA) was shown to be involved in the regulation of expression of drug metabolizing enzymes (DMEs) in rat primary hepatocytes in response to xenobiotics. Cytochrome P450 2B1 (CYP 2B1) is a DME that is dramatically induced by phenobarbital-type inducers. The constitutive androstane receptor (CAR) plays a critical role in regulating the expression of DMEs, and the phosphorylation/dephosphorylation of CAR is an important event in CYP 2B1 expression. In the present study, we determined the effect of DHA on MAPK transactivation and its role in CYP 2B1 expression induced by phenobarbital. c-Jun NH2-terminal kinase (JNK) JNK1/2 and ERK1/2 were activated by phenobarbital in a dose-dependent manner. DHA (100 μM) inhibited JNK1/2 and ERK2 activation induced by phenobarbital in a time-dependent manner. Both SP600125 (a JNK inhibitor) and SB203580 (a p38 MAPK inhibitor) inhibited CYP 2B1 protein and mRNA expression induced by phenobarbital. SB203580 significantly increased the intracellular 3′-5′-cyclic adenosine monophosphate (cAMP) concentration compared with a control group (p < 0.05). Our results suggest that inhibition of JNK activation by DHA is at least part of the mechanisms of DHA's downregulation of CYP 2B1 expression induced by phenobarbital.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3804 http://dx.doi.org/10.1016/j.jnutbio.2009.01.007
關聯:	Molecular Nutrition & Food Research,Volume 53, Issue 3, pages 341–348, March 2009
顯示於類別:	[營養學系暨碩士班] 期刊論文

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