Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, Zongping

doi:10.1038/s41598-018-21567-8

Cited by 63 publications

(42 citation statements)

References 47 publications

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“…Therefore, the increase in cell death, which was observed in cells treated with 20 and 40 µg/mL of ZEN, may be at least in part due to the overproduction of autophagic vesicles. Similar to our data, ZEN could induce autophagy by increasing beclin1, LC3-II, and autophagosomes in mouse and rat testicular cells [42,43]. Other potential mechanisms were reported in a recent publication where ZEN could induce the expression of cytochrome P450 reductase and oxidative stress, resulting in autophagy in porcine intestinal epithelial cells [44].…”

Section: Discussionsupporting

confidence: 91%

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Yoon

Lee²,

Seok

et al. 2019

Toxins

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Zearalenone (ZEN) is a mycotoxin produced by Fusarium species; however, its mechanisms of action in human livers have not been fully elucidated. Thus, we investigated the toxic mechanisms of ZEN in human liver cells. HepG2 cells were treated with ZEN (0–40 μg/mL) for up to 24 h. A significant decrease in cell viability was observed after treatment with 20 and 40 μg/mL of ZEN, including a significant increase in apoptosis and reactive oxygen species production. ZEN increased GRP78 and CHOP, and eIF2α phosphorylation, indicating ER stress; elevated transcription of the autophagy-associated genes, beclin1 and LC3, and translation of LC3; and increased phase I metabolism by increasing PXR and CYP3A4. The protein expression level of CYP3A4 was higher with ZEN treatment up to 20 μg/mL, but remained at the control level after treatment with 40 μg/mL ZEN. In phase II metabolism, Nrf2 activation and UGT1A expression were increased with ZEN treatment up to 20 μg/mL. Treating cells with an ER stress inhibitor alleviated ZEN-induced cell death and autophagy, and inhibited the expression of phase I/II enzymes. Overall, high ZEN concentrations can modulate the expression of phase I/II enzymes via ER stress and reduced protein levels in human liver cells.

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Section: Discussionsupporting

confidence: 91%

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Yoon

Lee²,

Seok

et al. 2019

Toxins

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“…In DU-145 cells, a similar increase was observed in p-p44-42 expression. The induction of the PI3K/Akt signaling pathway was previously associated both with ZEA-induced autophagy and oxidative stress [25,26]. Although the activation of the PI3K/Akt signaling pathway is mostly associated with the proliferation of cancer cells, similar to others, we observed increased phosphorylation of Akt in cells treated with ZEA + BAY as well as ZEA + BAY + PHTPP in LNCaP cells.…”

Section: Discussionsupporting

confidence: 87%

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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“…Previous studies have shown that the ER stress pathway has been reported to participate in oxidative damage and apoptosis induced by ZEN 22 – 24 , 46 . To provide further evidence that the A2 fermentation broth exerts a protective effect from ZEN-induced kidney injury, we explored whether the A2 fermentation broth could decrease both ER stress and apoptosis induced by ZEN.…”

Section: Discussionmentioning

confidence: 99%

Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice

Wang

Pan

et al. 2018

Sci Rep

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Zearalenone (ZEN) is an estrogen-like mycotoxin occurring in food and feeds, and it can cause oxidative damage and apoptosis in the testis, liver, and kidney. A current concern for researchers is how to reduce the harm it causes to humans and animals. In this study, our aim was to isolate and identify a novel and efficient ZEN-detoxifying strain of bacteria, and we aimed to assess the protective effect of the isolated strain on kidney damage caused by ZEN in mice. Our results indicated that a strain of Bacillus velezensis (B. velezensis), named A2, could completely degrade ZEN (7.45 μg/mL) after three days of incubation at 37 °C in the Luria-Bertani (LB) medium. This fermentation broth of the B. velezensis A2 strain was given to mice. The histopathological analysis indicated that the fermentation broth from the B. velezensis A2 strain reduced the degree of renal injury that is induced by ZEN. Furthermore, it greatly reduced the increase in serum levels of creatinine (CRE), uric acid (UA), and urea nitrogen (BUN) caused by ZEN. In addition, B. velezensis A2 strain also significantly inhibited the increase of malonaldehyde (MDA) content, and reversed the decreases of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities caused by ZEN. Studies have shown that ZEN is involved in the regulation of mRNA and protein levels of genes involved in the ER stress-induced apoptotic pathway, such as heavy chain binding protein (BIP), C-/-EBP homologous protein (CHOP), cysteine Aspartate-specific protease-12 (Caspase-12), c-Jun N-terminal kinase (JNK), and BCL2-related X protein (Bcl-2 and Bax). However, when mice were administered the fermentation broth of the B. velezensis A2 strain, it significantly reversed the expressions of these genes in their kidney tissue. In conclusion, our results indicate that the newly identified strain of B. velezensis A2, has a protective effect from renal injury induced by ZEN in mice. This strain has a potential application in the detoxification of ZEN in feed and protects animals from ZEN poisoning.

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Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells

Cited by 63 publications

References 47 publications

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

Zearalenone Induces Endoplasmic Reticulum Stress and Modulates the Expression of Phase I/II Enzymes in Human Liver Cells

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

Bacillus velezensis A2 fermentation exerts a protective effect on renal injury induced by Zearalenone in mice

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