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学科主题: 药学
题名:
Estrogen-related receptor ERR alpha-mediated downregulation of human hydroxysteroid sulfotransferase (SULT2A1) in Hep G2 cells
作者: Huang, Chaoqun1; Zhou, Tianyan2; Chen, Yue1; Sun, Teng1; Zhang, Shufen1; Chen, Guangping1
关键词: Sulfotransferase ; Estrogen-related receptor ; SULT2A1 ; Gene regulation ; Hep G2 cells
刊名: CHEMICO-BIOLOGICAL INTERACTIONS
发表日期: 2011-07-15
DOI: 10.1016/j.cbi.2011.04.002
卷: 192, 期:3, 页:264-271
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: CONSTITUTIVE ANDROSTANE RECEPTOR ; PREGNANE-X-RECEPTOR ; ACID-SULFOTRANSFERASE ; METHOTREXATE INDUCTION ; RESPONSE ELEMENT ; BILE-ACIDS ; EXPRESSION ; ACTIVATION ; GENE ; PROMOTER
英文摘要:

Hydroxysteroid sulfotransferase SULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotics. It plays an important role in the detoxification of hydroxyl-containing xenobiotics and in the regulation of the biological activities of hydroxysteroids. ERR alpha is an orphan member of the nuclear receptor superfamily that is closely related to estrogen receptor alpha (ER alpha). Here we report that the mRNA expression of human SULT2A1 was suppressed by ERR alpha in Hep G2 cells. To investigate the mechanisms of this regulation, the effects of ERR alpha on human SULT2A1 promoter transcription in Hep G2 cells were investigated. Reporter luciferase assay results showed that ERR alpha significantly represses human SULT2A1 promoter transcription in Hep G2 cells. Deletion analysis indicated that human SULT2A1 promoter region between positions -188 and -130 is necessary for its repression by ERR alpha in Hep G2 cells. The 5′ DNA -188 to -130 region of human SULT2A1 contains IR2 and DR4 hormone response elements and two putative ERR alpha response elements (ERREs) (ERRE188: GCAAGCTCA and ERRE155: ATAAGTTCA). Interestingly, ERRE188 overlaps with the IR2 element and ERRE155 overlaps with the DR4 element. Our further investigation demonstrated that ERR alpha represses human SULT2A1 promoter transcription by competing with other nuclear receptors for binding to IR2 or DR4 elements. The interaction of ERRE188 and ERRE155 elements with ERR alpha was confirmed by electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analysis. Our results suggest that ERR alpha may play an important role in regulating the metabolism of drugs and xenobiotics and in regulating endogenous hydroxysteroid activities via the regulation of SULT2A1. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

语种: 英语
所属项目编号: GM078606 ; RSG-07-028-01-CNE ; 2006-35200-17137 ; HR05-015
项目资助者: National Institutes of Health (NIH) ; American Cancer Society (ACS) ; United States Department of Agriculture (USDA) ; Oklahoma Center for the Advancement of Science and Technology (OCAST)
WOS记录号: WOS:000292573100011
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59946
Appears in Collections:北京大学药学院_药剂学系_期刊论文

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作者单位: 1.Oklahoma State Univ, Dept Physiol Sci, Ctr Vet Hlth Sci, Stillwater, OK 74078 USA
2.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China

Recommended Citation:
Huang, Chaoqun,Zhou, Tianyan,Chen, Yue,et al. Estrogen-related receptor ERR alpha-mediated downregulation of human hydroxysteroid sulfotransferase (SULT2A1) in Hep G2 cells[J]. CHEMICO-BIOLOGICAL INTERACTIONS,2011,192(3):264-271.
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