Ge Li-Chen, Chen Zhuo-Jia, Liu Hao, Zhang Kun-Shui, Su Qiao, Ma Xiang-Yu, Huang Hong-Bin, Zhao Zhen-Dong, Wang Yu-Ye, Giesy John P, Du Jun, Wang Hong-Sheng
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.
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.
Biochim Biophys Acta. 2014 Sep;1840(9):2663-73. doi: 10.1016/j.bbagen.2014.05.018. Epub 2014 Jun 5.
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.
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.
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.
Our study demonstrated that micromolar BPA inhibits proliferation of Sertoli cells by elevating oxidative stress while nanomolar BPA stimulates proliferation by promoting energy metabolism.
Micromolar BPA inhibits cell proliferation by elevating oxidative stress while nanomolar BPA stimulates cell proliferation by promoting energy metabolism.
双酚A（BPA）对细胞增殖的双相效应可在较低或较高暴露水平下出现。支持细胞在支持生殖细胞的增殖和分化中起关键作用。高浓度和低浓度BPA对支持细胞增殖产生相反作用的机制需要进一步研究。
我们利用蛋白质组学研究来鉴定用10⁻⁸M和10⁻⁵M BPA处理的支持TM4细胞的蛋白质表达变化。通过qRT-PCR和蛋白质免疫印迹分析研究了与线粒体、能量代谢和氧化应激相关的进一步机制。
蛋白质组学研究鉴定出36种蛋白质以及两个主要蛋白质簇，包括能量代谢和氧化应激相关蛋白，在用10⁻⁸M和10⁻⁵M BPA分别处理支持细胞24小时后，它们呈现相反的表达变化。暴露于10⁻⁵M BPA会导致更大的氧化应激，进而抑制细胞增殖，而活性氧清除剂NAC可有效阻断这些作用。暴露于10⁻⁸M BPA会导致细胞内ATP升高、线粒体活性增强，并导致TM4细胞显著增殖，而ATP合酶抑制剂寡霉素A消除了这些生长优势。
我们的研究表明，微摩尔浓度的BPA通过提高氧化应激来抑制支持细胞的增殖，而纳摩尔浓度的BPA通过促进能量代谢来刺激增殖。
微摩尔浓度的BPA通过提高氧化应激来抑制细胞增殖，而纳摩尔浓度的BPA通过促进能量代谢来刺激细胞增殖。
