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首页> 外文期刊>Journal of applied toxicology >The toxic effects of Bisphenol A on the mouse spermatocyte GC-2 cell line: the role of the Ca2+-calmodulin-Ca2+/calmodulin-dependent protein kinase II axis
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The toxic effects of Bisphenol A on the mouse spermatocyte GC-2 cell line: the role of the Ca2+-calmodulin-Ca2+/calmodulin-dependent protein kinase II axis

机译:双酚A对小鼠精子胶质细胞GC-2细胞系的毒性作用:Ca2 + -calmodulin-Ca2 + /钙调霉素依赖性蛋白激酶II轴的作用

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摘要

Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is known to induce male reproductive toxicity in rodents. However, its toxic effects on the germ cells are still poorly understood. It has been proposed that Ca2+ homeostasis and Ca2+ sensors, including calmodulin (CaM) and calmodulin-dependent protein kinase II (CaMKII), play critical roles in spermatogenesis. Therefore, in the present study, we aimed to investigate whether a perturbation in Ca2+-CaM-CaMKII signaling was involved in the BPA-induced injury to mouse spermatocyte GC-2spd (ts) (GC-2) cells. Our results showed that BPA (range from 0.2 to 20 M) induced obvious GC-2 cell injury, including decreased cell viability, the release of mitochondrial cytochrome c and the activation of caspase-3. However, these processes could be partially abrogated by pretreatment with a Ca2+ chelator (BAPTA/AM), a CaM antagonist (W7) or a CaMKII inhibitor (KN93). These results, taken together, indicate that BPA exposure contributes to male germ cell injury, which may be partially mediated through a perturbation in Ca2+/CaM/CaMKII signaling and the mitochondrial apoptotic process. Copyright (c) 2015 John Wiley & Sons, Ltd.
机译:众所周知,双酚A(BPA),内分泌破坏化学(EDC),用于诱导啮齿动物的雄性生殖毒性。然而,它对生殖细胞的毒性效应仍然明白。已经提出了Ca2 +稳态和Ca2 +传感器,包括钙调蛋白(CAM)和钙调蛋白依赖性蛋白激酶II(Camkii),在精子发生中起重要作用。因此,在本研究中,我们旨在研究CA2 + -CAM-CAMKII信令的扰动是否参与BPA诱导的小鼠精子胶质细胞GC-2SPD(TS)(GC-2)细胞的损伤。我们的研究结果表明,BPA(0.2至20米的范围为0.2至20米)诱导明显的GC-2细胞损伤,包括细胞活力下降,释放线粒体细胞色素C和Caspase-3的活化。然而,这些方法可以通过用Ca2 +螯合剂(Bapta / Am),CAM拮抗剂(W7)或CAMKII抑制剂(KN93)进行预处理。总之,这些结果表明BPA暴露有助于雄性细胞损伤,这可以通过CA2 + / CAMKII信令和线粒体凋亡过程的扰动部分介导。版权所有(c)2015 John Wiley&Sons,Ltd。

著录项

  • 来源
    《Journal of applied toxicology》 |2015年第12期|共7页
  • 作者单位

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Affiliated Jiangsu Canc Hosp Dept Oncol Nanjing 210009 Jiangsu Peoples R China;

    Jiangsu Univ Sch Med Sci &

    Lab Med Dept Prevent Med Zhenjiang 212013 Peoples R China;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

    Nanjing Med Univ Sch Publ Hlth Dept Toxicol Key Lab Modern Toxicol NJMU Minist Educ Nanjing;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学(毒理学);
  • 关键词

    Bisphenol A; GC-2 cells; apoptosis; calcium; calmodulin; calcium; calmodulin-dependent protein kinase II;

    机译:双酚A;GC-2细胞;细胞凋亡;钙;钙调蛋白;钙;钙调蛋白依赖性蛋白激酶II;

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