T-2 toxin inhibits gene expression and activity of key steroidogenesis enzymes in mouse Leydig cells

Yang, Jian Ying; Zhang, Yong Fa; Meng, Xiang Ping; Li, Yuan Xiao; Wang, Kai; Bai, Xue

doi:10.1016/j.tiv.2015.04.020

Cited by 24 publications

(10 citation statements)

References 27 publications

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“…Yang’s experiment has demonstrated that T-2 toxin has negative effects on male fertility and other reproductive pathologies [ 24 ]. More research has proven that TM3 cells are influenced by T-2 toxin in a dose-dependent manner and has revealed the mechanisms of cytotoxicity [ 25 , 26 , 27 , 28 ]. Our previous studies found that T-2 toxin decreased antioxidant scavenging enzymes, increased lipid peroxidation and ROS production, and contributed to TM3 cells apoptosis.…”

Section: Discussionmentioning

confidence: 99%

T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production

Wang

Yang

et al. 2018

IJMS

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Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ concentration changes was investigated using immunoblot assays in an in vitro model of TM3 cell injury induced by T-2 toxin. Changes in Ca2+ were assessed using the Ca2+-sensitive fluorescent indictor dye Fura 2-AM. The cytotoxicity of TM3 cells was assessed with an MTT bioassay, and apoptosis was measured using Annexin V-FITC staining. Following T-2 toxin treatment, the growth of cells, phospho-mTORSer2481, phospho-mTORSer2448, and phospho-AktSer473 were significantly decreased in a time-dependent manner, whereas Ca2+ and apoptosis were increased. T-2 toxin-induced apoptosis was prevented by BAPTA-AM (a Ca2+chelator) and MHY1485 (an mTOR activator), and the application of mTOR activator MHY1485 also prevented the increase of intracellular free Ca2+concentration in TM3 cells. Our results strongly suggest that T-2 toxin exposure induces apoptosis in TM3 cells by inhibiting mTORC2/AKT to promote Ca2+ production.

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Section: Discussionmentioning

confidence: 99%

T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production

Wang

Yang

et al. 2018

IJMS

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“…T-2 toxin represents a contaminant of considerable concern to human and animal health. At extremely high doses, it can cause shock-like syndrome that can result in death 3 . Deacetylation of T-2 toxin results in HT-2 toxin, which was the major metabolite of T-2 toxin 4 .…”

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confidence: 99%

Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes

Zhang

Han

Zhu

et al. 2016

Sci Rep

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T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation.

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“…The isolation and the purification of Leydig cells were performed according to our previous methods . Leydig cells were isolated from testes of 60‐day to 90‐day Kunming mice.…”

Section: Methodsmentioning

confidence: 99%

l‐arginine protects against oxidative damage induced by T‐2 toxin in mouse Leydig cells

Yang

Zhang

et al. 2018

J Biochem & Molecular Tox

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To explore the protective mechanism of l-arginine against T-2 toxin-induced oxidative damage in mouse Leydig cells, Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), l-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) with l-arginine (0.25, 0.5, or 1.0 mM) for 24 hours. Cells and supernatants were harvested to examine cell viability, activities, and messenger RNA (mRNA) expression of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), malondialdehyde (MDA) content, and DNA damage. Results showed that T-2 toxin significantly reduced cell viability, improved MDA content and DNA damage, and decreased activities and mRNA expression of GSH-Px, SOD, and CAT. However, l-arginine reduced T-2 toxin-induced oxidative damage and tended to maintain normal levels. Furthermore, l-arginine upregulated mRNA expressions of GSH-Px, SOD, and CAT. Collectively, l-arginine, due to its antioxidative ability, could ameliorate T-2 toxin-induced cytotoxicities in mouse Leydig cells by regulating oxidative stress.

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T-2 toxin inhibits gene expression and activity of key steroidogenesis enzymes in mouse Leydig cells

Cited by 24 publications

References 27 publications

T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production

T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production

Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes

l‐arginine protects against oxidative damage induced by T‐2 toxin in mouse Leydig cells

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