IR@PKUHSC  > 北京大学药学院  > 化学生物学系
学科主题药学
Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression
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
2013-02-15
DOI10.1016/j.taap.2012.12.014
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
资助者Project 973 ; Hundred-Talent Project, CAS ; NSF China Outstanding Youth Award ; NSFC ; NIH ; Project 973 ; Hundred-Talent Project, CAS ; NSF China Outstanding Youth Award ; NSFC ; NIH
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
资助者Project 973 ; Hundred-Talent Project, CAS ; NSF China Outstanding Youth Award ; NSFC ; NIH ; Project 973 ; Hundred-Talent Project, CAS ; NSF China Outstanding Youth Award ; NSFC ; NIH
WOS记录号WOS:000314626300009
Citation statistics
Cited Times:18[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61532
Collection北京大学药学院_化学生物学系
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
GB/T 7714
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.
APA Sheng, Zhi-Guo,Huang, Wei,Liu, Yu-Xiang,&Zhu, Ben-Zhan.(2013).Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression.TOXICOLOGY AND APPLIED PHARMACOLOGY,267(1),88-94.
MLA Sheng, Zhi-Guo,et al."Bisphenol A at a low concentration boosts mouse spermatogonial cell proliferation by inducing the G protein-coupled receptor 30 expression".TOXICOLOGY AND APPLIED PHARMACOLOGY 267.1(2013):88-94.
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