title: Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell proliferation: a comparative proteomic analysis.
abstract: BACKGROUND
  Biphasic effects on cell proliferation of bisphenol A (BPA) can occur at lesser or greater exposures. Sertoli cells play a pivotal role in supporting proliferation and differentiation of germ cells. The mechanisms responsible for inverse effects of great and low concentrations of BPA on Sertoli cell proliferation need further study.
  
  
  METHODS
  We utilized proteomic study to identify the protein expression changes of Sertoli TM4 cells treated with 10(-8)M and 10(-5)M BPA. The further mechanisms related to mitochondria, energy metabolism and oxidative stress were investigated by qRT-PCR and Western-blotting analysis.
  
  
  RESULTS
  Proteomic studies identified 36 proteins and two major clusters of proteins including energy metabolism and oxidative stress expressed with opposite changes in Sertoli cells treated with 10(-8)M and 10(-5)M BPA, respectively, for 24h. Exposure to 10(-5)M BPA resulted in greater oxidative stress and then inhibited cell proliferation, while ROS scavenger NAC effectively blocked these effects. Exposure to 10(-8)M BPA caused higher intercellular ATP, greater activities of mitochondria, and resulted in significant proliferation of TM4 cells, while oligomycin A, an inhibitor of ATP synthase, abolished these growth advantages.
  
  
  CONCLUSIONS
  Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism.
  
  
  CONCLUSIONS
  Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.
authors.affiliation: Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Ge
authors.affiliation: Department of Pharmacy, Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Zhuo-Jia
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Cancer Research Institute and Cancer Hospital, Guangzhou Medical University, Guangzhou 510095, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
authors.forename: Kun-Shui
authors.initials: KS
authors.lastname: Zhang
authors.affiliation: Laboratory Animal Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Su
authors.affiliation: Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Ma
authors.affiliation: Department of Pharmacy, Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Huang
authors.affiliation: School of Chinese Materia Medica, Guangdong Food and Drug Vocational College, No. 321 Longdongbei Road, Guangzhou 510520, China.
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Zhao
authors.affiliation: Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China.
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Veterinary Biomedical Sciences & Toxicological Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: dujun@mail.sysu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, No. 132 Waihuandong Road, University Town, Guangzhou 510006, China. Electronic address: whongsh@mail.sysu.edu.cn.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000395:Air Pollutants, Occupational / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism*; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D010636:Phenols; D020543:Proteome; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Energy metabolism; In vitro; Oxidative stress; Proliferation; Proteomics; TM4 cell