Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in Zearalenone-treated mouse endometrial stromal cells

Hu, Jin; Xu, Minglong; Dai, Yujian; Xiao-lin, Ding; Cheng, Xiangdong; Ji, Hongjun; Xu, Yinxue

doi:10.1016/j.bbrc.2016.05.161

Cited by 37 publications

(16 citation statements)

References 39 publications

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“…Therefore, the ratio of Bax/Bcl‐2 is one of the key factors to determine the survival and death of cells . After exposure to different concentrations of ZEA, the ratio of Bax/Bcl‐2 was increased at both protein and gene levels in mouse stromal cells . In this study, Bax protein increased and Bcl‐2 protein decreased after exposure to different concentrations of ZEA in Sertoli cells, and the results of qRT‐PCR were consistent with those of Western blot.…”

Section: Discussionsupporting

confidence: 82%

“…ZEA can activate mitochondrial pathways dependent on caspase‐3 and caspase‐9, and induce apoptosis and necrosis of pig granulosa cells in a dose‐dependent manner . After exposure to ZEA, the expression of Bax in mouse endometrial epithelial cells increased in a dose‐dependent manner, whereas the expression of Bcl‐2 was reversed, and caspase‐3 and caspase‐9 were activated . ZEA can release cytochrome C from mitochondria into cytoplasm, decrease mitochondrial transmembrane potential, activate caspase‐3 and caspase‐8, produce reactive oxygen species and induce apoptosis of HL‐60U937 and PBMCs under endoplasmic reticulum stress .…”

Section: Discussionmentioning

confidence: 99%

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Zearalenone induces apoptosis of rat Sertoli cells through Fas‐Fas ligand and mitochondrial pathway

Cai

et al. 2019

Environmental Toxicology

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Zearalenone (ZEA) is an estrogen-like toxin produced by Fusarium that is widely found in cereals worldwide. In recent years, ZEA has been found to cause reproductive dysfunction in male animals, but the underlying mechanism remains unclear. This study examined the apoptosis of rat Sertoli cells induced by different concentrations (0, 5, 10, and 20 μmol/L) of ZEA via Fas-Fas ligand and mitochondrial signaling pathway in vitro. Apoptosis rate was detected by flow cytometry. The mitochondrial membrane potential was detected by immunofluorescence assay and flow cytometry. Western Blot and qRT-PCR were used to identify the signaling pathway. The results revealed that ZEA induced apoptosis of rat Sertoli cells, significantly reduced the transcription and expression of the anti-apoptotic protein Bcl-2, increased the transcription and expression of pro-apoptotic proteins Bax and tBID, and Fas, FasL, FADD, and caspase-8. ZEA also increased the activation of caspase-8 and caspase-9, and promoted the release of cytochrome C from mitochondria to cytoplasm. Moreover, addition of caspase-8 inhibitor Z-IETD-FMK led to significant decrease in the mitochondrial membrane potential and apoptosis rate of the ZEA + Z-IETD-FMK group as compared to the ZEA treatment group. The release of cytochrome C from mitochondria to cytoplasm and the activation of caspase-9 and caspase-3 were significantly decreased in the ZEA + Z-IETD-FMK group. These results suggested that ZEA can induce apoptosis of rat Sertoli cells, activate the Fas-Fas ligand signaling pathway and participate in the regulation of mitochondrial apoptosis pathway. K E Y W O R D S apoptosis, Fas ligand, mitochondria, Sertoli cells, Zearalenone | INTRODUCTIONZearalenone (ZEA), also known as F-2 toxin, is a mycotoxin produced by fusarium spp, which is commonly found in feed and food. In nature, animals cannot avoid eating or touching feed or raw materials containing ZEA. 1 ZEA is structurally similar to estrogen, and can compete with estrogen to bind estrogen receptor, thus interfering with the effect of estrogen. 2 ZEA also has a similar structure to steroids. By competitive binding of 3α-HSD and 3β-HSD, the synthesis of reproductive hormones is affected, which leads to disorders of reproductive system function. 3 The estrogen receptor is the main target of zearalenone and its metabolites. 4 Early studies found that the degradation rate of porcine oocytes increased with the increase of α-ZEA and β-ZEA doses. 5 A study in which cows were fed with ZEA containing feeds showed that the pregnant cows had oestrus, while the pubertal cows were estrous but sterile. 6 ZEA can also affect the reproduction of male animals. High dose of ZEA and its metabolites could reduce the survival rate of sperms, increase the rate of deformity and mortality, decrease the concentration of sperms, and damage the reproductive function of male animals. 7,8 Cheraghi et al. showed that the interaction of cyclin D1 and E2F1 during mitosis resulted in an increase in apoptosis after subcutaneous injection of 1-...

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Zearalenone induces apoptosis of rat Sertoli cells through Fas‐Fas ligand and mitochondrial pathway

Cai

et al. 2019

Environmental Toxicology

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“…It is a common fungal contaminant of cereal crops worldwide and is typically found in feed and grains, including maize, wheat and rye (55). ZEA is structurally similar to estrogen and competes with estradiol for binding to estrogen receptors, and stimulates estrogenic activity, which may cause several physiological alterations in the reproductive tract (56). In vitro study has indicated that ZEA may regulate metabolic processes, including cell proliferation, differentiation and apoptosis (57).…”

Section: Discussionmentioning

confidence: 99%

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

Wang

Zhao

et al. 2018

Mol Med Report

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Increased endometrial stromal cell (ESC) survival and migration is responsible for the development and progression of endometriosis. However, little is known about the mechanisms underlying ESC survival and migration, and limited therapeutic strategies that are able to reverse these abnormalities are available. The present study investigated the effects of zearalenone (ZEA) on ESC survival and migration, particularly focusing on mitochondrial fission and the c‑Jun N‑terminal kinase (JNK)/dynamin‑related protein 1 (Drp1) pathway. The results revealed that ZEA induced ESC apoptosis in a dose‑dependent manner. Furthermore, ZEA treatment triggered excessive mitochondrial fission resulting in structural and functional mitochondrial damage, leading to the collapse of the mitochondrial membrane potential and subsequent leakage of cytochrome c into the cytoplasm. This triggered the mitochondrial pathway of apoptosis. Additionally, ZEA‑induced mitochondrial fission decreased ESC migration through F‑actin/G‑actin homeostasis dysregulation. ZEA also increased JNK phosphorylation and subsequently Drp1 phosphorylation at the serine 616 position, resulting in Drp1 activation. JNK/Drp1 pathway inhibition abolished the inhibitory effects of ZEA on ESC survival and migration. In summary, the present study demonstrated that ZEA reduced ESC survival and migration through the stimulation of mitochondrial fission by activation of the JNK/Drp1 pathway.

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“…Caspase-3 is the most significant effector protease in apoptosis (Galluzzi, Kepp, & Kroemer, 2012). Bax and Bcl-2 are proapoptosis and anti-apoptosis proteins, respectively, and the ratio of Bax/Bcl-2 is important in regulating the release of cytochrome c, which then activates caspase-3 and induces apoptosis (Hu et al, 2016). In this study, flow cytometric data indicated that the percentage of early and For confirmation of the safety-in-use of SDAPR, a standard battery of toxicity studies was performed to assess the potential to induce toxicity in rodents.…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity in vitro and biological safety evaluation in vivo of Sika deer antler protein

Yang

Wang²,

Sun

et al. 2017

J Food Biochem

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This study evaluated the antitumor activity in vitro and biological safety in vivo of Sika deer antler protein (SDAPR). MTT and plate cloning assays were used for anti‐proliferation assessment of prostate cancer cells (PC‐3M) while flow cytometry and western blot were used for apoptosis analysis. In addition, biological safety of SDAPR was evaluated by acute oral toxicity test, bone marrow micronucleus assay and sperm aberration experiment. The results showed that SDAPR could suppress proliferation capacity and induce apoptosis on PC‐3M cells. No adverse effects were observed in Kunming mice following acute oral gavage with SDAPR at a dose of 8 g/kg body weight. The negative results obtained in bone marrow micronucleus test and sperm malformation assay demonstrated that SDAPR had no obvious toxicity to cause mutagenicity. In conclusion, SDAPR exerts anti‐tumor effect with high biological safety, which suggested that it could be used as a potential chemotherapeutic agent for human health. Practical applications It demonstrates that Sika deer antler protein has anticancer effects and high biological safety on prostate cancer cells. In addition, this paper provides scientific basis for treating tumors with Sika deer antler.

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Exploration of Bcl-2 family and caspases-dependent apoptotic signaling pathway in Zearalenone-treated mouse endometrial stromal cells

Cited by 37 publications

References 39 publications

Zearalenone induces apoptosis of rat Sertoli cells through Fas‐Fas ligand and mitochondrial pathway

Zearalenone induces apoptosis of rat Sertoli cells through Fas‐Fas ligand and mitochondrial pathway

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway

Anticancer activity in vitro and biological safety evaluation in vivo of Sika deer antler protein

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