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

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 mechani...

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Autores principales: Wang, Bing-jie, Zheng, Wang-long, Feng, Nan-nan, Wang, Tao, Zou, Hui, Gu, Jian-hong, Yuan, Yan, Liu, Xue-zhong, Liu, Zong-ping, Bian, Jian-chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215106/
https://www.ncbi.nlm.nih.gov/pubmed/30274213
http://dx.doi.org/10.3390/toxins10100398
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author Wang, Bing-jie
Zheng, Wang-long
Feng, Nan-nan
Wang, Tao
Zou, Hui
Gu, Jian-hong
Yuan, Yan
Liu, Xue-zhong
Liu, Zong-ping
Bian, Jian-chun
author_facet Wang, Bing-jie
Zheng, Wang-long
Feng, Nan-nan
Wang, Tao
Zou, Hui
Gu, Jian-hong
Yuan, Yan
Liu, Xue-zhong
Liu, Zong-ping
Bian, Jian-chun
author_sort Wang, Bing-jie
collection PubMed
description 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.
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spelling pubmed-62151062018-11-13 The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone Wang, Bing-jie Zheng, Wang-long Feng, Nan-nan Wang, Tao Zou, Hui Gu, Jian-hong Yuan, Yan Liu, Xue-zhong Liu, Zong-ping Bian, Jian-chun Toxins (Basel) Article 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. MDPI 2018-09-28 /pmc/articles/PMC6215106/ /pubmed/30274213 http://dx.doi.org/10.3390/toxins10100398 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Bing-jie
Zheng, Wang-long
Feng, Nan-nan
Wang, Tao
Zou, Hui
Gu, Jian-hong
Yuan, Yan
Liu, Xue-zhong
Liu, Zong-ping
Bian, Jian-chun
The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title_full The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title_fullStr The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title_full_unstemmed The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title_short The Effects of Autophagy and PI3K/AKT/m-TOR Signaling Pathway on the Cell-Cycle Arrest of Rats Primary Sertoli Cells Induced by Zearalenone
title_sort effects of autophagy and pi3k/akt/m-tor signaling pathway on the cell-cycle arrest of rats primary sertoli cells induced by zearalenone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215106/
https://www.ncbi.nlm.nih.gov/pubmed/30274213
http://dx.doi.org/10.3390/toxins10100398
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