2. Academic Validation
  3. ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway

  • Toxins (Basel). 2018 Jan 1;10(1):24. doi: 10.3390/toxins10010024.
Wang-Long Zheng 1 2 3 4,  Bing-Jie Wang 5 6 7,  Ling Wang 8 9 10,  Yu-Ping Shan 11,  Hui Zou 12 13 14,  Rui-Long Song 15 16 17,  Tao Wang 18 19 20,  Jian-Hong Gu 21 22 23,  Yan Yuan 24 25 26,  Xue-Zhong Liu 27 28 29,  Guo-Qiang Zhu 30 31 32,  Jian-Fa Bai 33,  Zong-Ping Liu 34 35 36,  Jian-Chun Bian 37 38 39
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. zhengwanglong@163.com.
  • 2 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. zhengwanglong@163.com.
  • 3 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. zhengwanglong@163.com.
  • 4 Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. zhengwanglong@163.com.
  • 5 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. wangbingjie123188@163.com.
  • 6 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. wangbingjie123188@163.com.
  • 7 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. wangbingjie123188@163.com.
  • 8 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. wl7590@163.com.
  • 9 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. wl7590@163.com.
  • 10 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. wl7590@163.com.
  • 11 Lianyungang Husbandry and Veterinary Station, Lianyungang 222001, China. lygsyp8@126.com.
  • 12 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. zouhui@yzu.edu.cn.
  • 13 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. zouhui@yzu.edu.cn.
  • 14 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. zouhui@yzu.edu.cn.
  • 15 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. srlbio@163.com.
  • 16 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. srlbio@163.com.
  • 17 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. srlbio@163.com.
  • 18 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. wtao6550@yzu.edu.cn.
  • 19 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. wtao6550@yzu.edu.cn.
  • 20 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. wtao6550@yzu.edu.cn.
  • 21 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. jhgu@yzu.edu.cn.
  • 22 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. jhgu@yzu.edu.cn.
  • 23 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. jhgu@yzu.edu.cn.
  • 24 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. yuanyan@yzu.edu.cn.
  • 25 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. yuanyan@yzu.edu.cn.
  • 26 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. yuanyan@yzu.edu.cn.
  • 27 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. liuxuezhong68@163.com.
  • 28 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. liuxuezhong68@163.com.
  • 29 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. liuxuezhong68@163.com.
  • 30 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. yzgqzhu@yzu.edu.cn.
  • 31 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. yzgqzhu@yzu.edu.cn.
  • 32 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. yzgqzhu@yzu.edu.cn.
  • 33 Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. jbai@vet.k-state.edu.
  • 34 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. liuzongping@yzu.edu.cn.
  • 35 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. liuzongping@yzu.edu.cn.
  • 36 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. liuzongping@yzu.edu.cn.
  • 37 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. jcbian@yzu.edu.cn.
  • 38 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. jcbian@yzu.edu.cn.
  • 39 Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. jcbian@yzu.edu.cn.
PMID: 29301253 DOI: 10.3390/toxins10010024
Abstract

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.

Keywords

AMPK signaling; ER stress; ROS; Sertoli cells; Zearalenone; cell apoptosis; cell cycle.

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