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Toxins 2018, 10(1), 24; doi:10.3390/toxins10010024

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

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College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
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Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
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Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
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Kansas State Veterinary Diagnostic Laboratory, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
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Lianyungang Husbandry and Veterinary Station, Lianyungang 222001, China
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Authors to whom correspondence should be addressed.
Received: 1 December 2017 / Revised: 21 December 2017 / Accepted: 28 December 2017 / Published: 1 January 2018
(This article belongs to the Collection Fusarium Toxins – Relevance for Human and Animal Health)
View Full-Text   |   Download PDF [6550 KB, uploaded 1 January 2018]   |  

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. View Full-Text
Keywords: Zearalenone; cell cycle; cell apoptosis; ROS; ER stress; AMPK signaling; Sertoli cells Zearalenone; cell cycle; cell apoptosis; ROS; ER stress; AMPK signaling; Sertoli cells
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Zheng, W.-L.; Wang, B.-J.; Wang, L.; Shan, Y.-P.; Zou, H.; Song, R.-L.; Wang, T.; Gu, J.-H.; Yuan, Y.; Liu, X.-Z.; Zhu, G.-Q.; Bai, J.-F.; Liu, Z.-P.; Bian, J.-C. ROS-Mediated Cell Cycle Arrest and Apoptosis Induced by Zearalenone in Mouse Sertoli Cells via ER Stress and the ATP/AMPK Pathway. Toxins 2018, 10, 24.

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