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

Zheng, Wanglong; Wang, Bingjie; Wang, Ling; Shan, Yuping; Zou, Hui; Song, Ruilong; Wang, Tao; Gu, Jianhong; Yuan, Yan; Zhu, Guoqiang; Bai, Jianfa; Liu, Zongping; Bian, Jianchun

doi:10.3390/toxins10010024

Cited by 96 publications

(72 citation statements)

References 32 publications

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“…This observation might be associated with the fact that these two cell lines represent a different models of PCa with a different differentiation ratio and invasiveness of cells. A cell cycle arrest in the G2/M phase associated with ZEA-induced oxidative stress has also been observed by others [22,23]. The MAPK and PI3K/Akt cell signaling pathways are reported to be involved in ZEA-induced effects in cells [24].…”

Section: Discussionsupporting

confidence: 60%

ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

Kowalska

Habrowska-Górczyńska

Domińska

et al. 2020

Toxins

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Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) is commonly expressed in prostate cancer (PCa) cells and is associated with increased proliferation, metastases and androgen independence. Zearalenone (ZEA) is one of the most common mycotoxins contaminating food, which might mimic estrogens and bind to estrogen receptors (ERs). The ratio of androgens to estrogens in men decreases physiologically with age, and is believed to participate in prostate carcinogenesis. In this study, we evaluated the role of NFκB and ERβ in the induction of oxidative stress in human PCa cells by ZEA. As observed, ZEA at a dose of 30 µM induces oxidative stress in PCa cells associated with DNA damage and G2/M cell cycle arrest. We also observed that the inhibition of ERβ and NFΚB via specific inhibitors (PHTPP and BAY 117082) significantly increased ZEA-induced oxidative stress, although the mechanism seems to be different for androgen-dependent and androgen-independent cells. Based on our findings, it is possible that the activation of ERβ and NFΚB in PCa might protect cancer cells from ZEA-induced oxidative stress. We therefore shed new light on the mechanism of ZEA toxicity in human cells.

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Section: Discussionsupporting

confidence: 60%

ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

Kowalska

Habrowska-Górczyńska

Domińska

et al. 2020

Toxins

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“…Apart from regulating AJs integrity, SCs proliferation inhibition is also mediated by the AMPK signaling pathway 98 . AMPK activation potentially leads to detention of rat SCs proliferation at least partially by inhibition of mTORC1 and stimulation of cyclin-dependent kinase inhibitors expression.…”

Section: Scs Proliferationmentioning

confidence: 99%

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

2019

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The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells’ mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.

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“…Zearalenone (ZEN) is widely distributed mycotoxin, produced by Fusarium species and can exert estrogen-like activity. Zheng et al [71] reported ZEN-induced germ cell death by ROS mediated ER stress in mouse Sertoli cell. Furthermore, ER stress regulates ATP/AMPK pathway, suggest crosstalk between ROS-mediated ER stress and ATP/AMPK pathway and plays key role in ZEN induced cell cycle arrest and cell apoptosis.…”

Section: Involvement Of Endoplasmic Reticulum Stress In Testis and Gementioning

confidence: 99%

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

Karna

Shin

Choi

et al. 2020

World J Mens Health

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Endoplasmic reticulum (ER) stress, defined as prolonged disturbances in protein folding and accumulation of unfolded proteins in the ER. Perturbation of the ER, such as distribution of oxidative stress, iron imbalance, Ca 2+ leakage, protein overload, and hypoxia, can cause ER stress. The cell reacts to ER stress by activating protective pathways, called the unfolded protein response (UPR), which is comprised of cellular mechanisms aimed for maintaining cellular homeostasis or, in case of excessively severe stress, at the initiation of cellular apoptosis. The three UPR signaling pathways from the ER stress sensors are initiated by activating transcription factor 6, inositol requiring enzyme 1, and protein kinase RNA-activated-like ER kinase. A number of physiological and pathological conditions, environmental toxicants and variety of pharmacological agents showed disruption of proper ER functions and thereby cause ER stress in male reproductive organ in rat model. The present review summarizes the existing data concerning the molecular and biological mechanism of ER stress in male reproduction and male infertility. ER stress initiated cell death pathway has been related to several diseases, including hypoxia, heath disease, diabetes, and Parkinson's disease. Although there is not enough evidence to prove the relationship between ER stress and male infertility in human, most studies in this review found that ER stress was correlated with male reproduction and infertility in animal models. The ER stress could be novel signaling pathway of regulating male reproductive cellular apoptosis. Infertility might be a result of disturbing the ER stress response during the process of male reproduction. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

Cited by 96 publications

References 32 publications

ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

ERβ and NFκB—Modulators of Zearalenone-Induced Oxidative Stress in Human Prostate Cancer Cells

Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review

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