College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
Toxins (Basel). 2018 Jan 1;10(1):24. doi: 10.3390/toxins10010024.
Zearalenone (ZEA) can perturb the differentiation of cells, reduce the generation of reproductive cells and induce a death of germ cells, but the molecular mechanism remains unclear. In order to investigate the potential mechanism of ZEA-induced cell cycle arrest and apoptosis, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins, cell death, cell apoptosis, ROS generation and the ATP/AMPK pathway in Sertoli cells. The role of ROS, ER stress and the ATP/AMPK pathway in ZEA-induced cell-cycle arrest and cell apoptosis was explored by using the antioxidant NAC, ER stress inhibitor 4-PBA and the AMPK inhibitor dorsomorphin, respectively. The results revealed that ZEA inhibited the cell proliferation, influenced the distribution of the cell cycle and induced cell apoptosis through the ATP/AMPK pathway. The ATP/AMPK pathway was regulated by ER stress that was induced by ROS generation after exposure to ZEA. Taking these together, this study provided evidence that ROS regulated the process of ZEA-induced cell cycle arrest and cell apoptosis through ER stress and the ATP/AMPK signal ways.
玉米赤霉烯酮（ZEA）可以干扰细胞分化，减少生殖细胞的产生，并诱导生殖细胞死亡，但分子机制尚不清楚。为了研究 ZEA 诱导细胞周期停滞和细胞凋亡的潜在机制，我们研究了 ZEA 对支持细胞增殖、细胞周期分布、细胞周期相关蛋白、细胞死亡、细胞凋亡、ROS 生成和 ATP/AMPK 通路的影响。通过使用抗氧化剂 NAC、内质网应激抑制剂 4-PBA 和 AMPK 抑制剂 dorsomorphin，分别研究了 ROS、内质网应激和 ATP/AMPK 通路在 ZEA 诱导的细胞周期停滞和细胞凋亡中的作用。结果表明，ZEA 通过 ATP/AMPK 通路抑制细胞增殖、影响细胞周期分布并诱导细胞凋亡。ROS 生成诱导的内质网应激调节了 ATP/AMPK 通路。综上所述，本研究提供的证据表明，ROS 通过内质网应激和 ATP/AMPK 信号通路调节 ZEA 诱导的细胞周期停滞和细胞凋亡过程。
