2. Academic Validation
  3. The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone

The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone

  • Toxins (Basel). 2018 Sep 28;10(10):398. doi: 10.3390/toxins10100398.
Bing-Jie Wang 1 2 3,  Wang-Long Zheng 4 5,  Nan-Nan Feng 6 7,  Tao Wang 8 9,  Hui Zou 10 11,  Jian-Hong Gu 12 13,  Yan Yuan 14 15,  Xue-Zhong Liu 16 17,  Zong-Ping Liu 18 19 20,  Jian-Chun Bian 21 22 23
Affiliations

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 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 5 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 6 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 7 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 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 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 11 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, 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 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 15 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China. [email protected].
  • 16 College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China. [email protected].
  • 17 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 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].
PMID: 30274213 DOI: 10.3390/toxins10100398
Abstract

A high concentration of Zearalenone (ZEA) will perturb the differentiation of germ cells, and induce a death of germ cells, but the toxic mechanism and molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable role in spermatogenesis. In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of Autophagy and PI3K/Akt/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the Autophagy promoter RAPA, Autophagy Inhibitor CQ, and the PI3K Inhibitor LY294002, respectively. The data revealed that ZEA could inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase and trigger the Autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway. Promoting or inhibiting the level of Autophagy could either augment or reverse the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling pathway. Taken together, this study provides evidence that Autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced Autophagy plays a protective role in this process.

Keywords

Autophagy; G2/M arrest; PI3K/Akt/m TOR signaling; Sertoli cells (SCs); Zearalenone (ZEA); cell cycle.

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