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
  • 1. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 2. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 3. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 4. Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. [email protected].
  • 5. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 6. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 7. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 8. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 9. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 10. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 11. Lianyungang Husbandry and Veterinary Station, Lianyungang 222001, China. [email protected].
  • 12. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 13. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 14. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 15. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 16. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 17. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 18. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 19. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 20. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 21. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 22. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 23. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 24. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 25. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 26. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 27. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 28. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 29. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 30. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 31. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 32. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 33. Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA. [email protected].
  • 34. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 35. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 36. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 37. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 38. Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 39. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China. [email protected].
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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