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学科主题: 药学
题名:
Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression
作者: Sheng, Zhi-Guo1; Huang, Wei2; Liu, Yu-Xiang1; Zhu, Ben-Zhan1,3
关键词: Bisphenol A ; G protein-coupled receptor 30 ; c-Fos ; Activator protein 1 site ; Mouse spermatogonial GC-1 cells
刊名: TOXICOLOGY AND APPLIED PHARMACOLOGY
发表日期: 2013-02-15
DOI: 10.1016/j.taap.2012.12.014
卷: 267, 期:1, 页:88-94
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: BREAST-CANCER CELLS ; HUMAN ESTROGEN-RECEPTOR ; C-FOS PROTOONCOGENE ; OVARIAN-CANCER ; GPR30 ; ACTIVATION ; ALPHA ; GROWTH ; RESISTANCE ; MECHANISM
英文摘要:

Bisphenol A (BPA) is one of the most prevalent chemicals in daily-use materials, therefore, human exposure to BPA is ubiquitous. We found that low concentrations of BPA stimulate the spermatogonial GC-1 cells proliferation by G protein-coupled receptor 30 (GPR30)-mediated epidermal growth factor receptor (EGFR)-extracellular regulated kinase (ERK)-c-Fos pathway. However, through the same pathway GPR30 expression has been shown to be induced by EGF, an EGFR ligand. Thus, we want to know if low concentrations of BPA are able to induce the GPR30 expression and the possible mechanism(s) in GC-1 cells. By transient transfection with expression plasmids, 10(-9) M EPA significantly transactivates the Gpr30-5′-flanking region through activating the GPR30, cGMP-dependent protein kinase (PKG), estrogen receptor-alpha (ER-alpha), and EFGR-ERK pathways. Furthermore, an activator protein-1 (AP-1) site located within this region is found to be responsible for the transactivation of BPA. Expectedly, through the same pathways, BPA significantly induces the gene and protein expression of GPR30. c-Fos is further observed to be strongly recruited to the AP-1 site in a chromatin immunoprecipitation assay and its dysfunction on the AP-1 site markedly suppresses the expression of GPR30, p-ERK1/2, p-Ser118-ER-alpha and cell proliferation by BPA. Our results demonstrate that a low-concentration BPA induces GPR30 expression through the GPR30-EFGR-ERK-c-Fos, ER-alpha, and PKG pathways, presumably boosting the cells proliferation via a regulatory loop. The present study provides a novel insight into the potential role of GPR30 in the initiation and progression of male germ cell cancer induced by environmentally relevant BPA. (C) 2012 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 2008CB418106 ; 20925724 ; 20907070 ; 20877081 ; 20890112 ; 20921063 ; 21207139 ; 21237005 ; ES11497 ; RR01008 ; ES00210
项目资助者: Project 973 ; Hundred-Talent Project, CAS ; NSF China Outstanding Youth Award ; NSFC ; NIH
WOS记录号: WOS:000314626300009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61532
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Chinese Acad Sci, State Key Lab Environm Chem & Ecotoxicol, Ecoenvironm Sci Res Ctr, Beijing 100085, Peoples R China
2.Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, Hlth Sci Ctr, Beijing 100091, Peoples R China
3.Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA

Recommended Citation:
Sheng, Zhi-Guo,Huang, Wei,Liu, Yu-Xiang,et al. Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2013,267(1):88-94.
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