T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through reactive oxygen species-mediated mitochondrial pathway

Abstract

T-2 toxin, a member of the trichothecene mycotoxin family produced by the Fusarium fungi, has been shown to exert a variety of toxic effects on multiple targets in vivo. However, the embryonic toxicity of T-2 toxin in vitro remains unclear. In the present study, two permanent cell lines, embryonic stem cells (ES cells D3) and fibroblast 3T3 cells, were used to evaluate T-2 toxin toxicity. Differentiated mouse ES cells were cultivated as embryoid bodies along with T-2 toxin at different concentrations (0.5, 1, and 2 ng/ml) for 24 h. The increases in cellular reactive oxygen species (ROS), lipid and DNA oxidative damage, and loss of mitochondrial transmembrane potential were observed at 1 and 2 ng/ml concentrations. Flow cytometry showed that T-2 toxin induced cell cycle arrest and apoptosis. Furthermore, T-2 toxin opened the mitochondrial permeability transition pore, caused the release of cytochrome c from mitochondria and induced the upregulation of p53, caspase-9, caspase-3 expression and increased the ratio of Bax/Bcl-2. However, T-2 toxin-induced oxidative damage and apoptosis in differentiated ES cells decreased significantly in the presence of the antioxidant Trolox. Taken together, these results demonstrate that T-2 toxin induces oxidative stress and apoptosis in differentiated murine ES cells, and ROS-mediated mitochondrial pathway plays an important role in T-2 toxin induced apoptosis.

Toxic effects of T-2 toxin and deoxynivalenol on the mitochondrial electron transport system of cardiomyocytes in rats

“…Therefore, it is considered that the mitochondrial dysfunction due to T-2 toxin is largely associated with production of reactive oxygen species in the mitochondria and/or cytoplasm surrounding the mitochondria. A recent study (Fang et al, 2012) that showed that T-2 toxin-induced cell damage and apoptosis were caused by the reactive oxygen species-mediated mitochondrial pathway also confirms such a possibility. The examination of effects of antioxidants on DON toxicity was not performed in the present study.…”

Toxic effects of HT-2 toxin on mouse oocytes and its possible mechanisms

“…Previous studies showed that T-2 toxin induced apoptosis in differentiated murine embryonic stem cells and ovarian granulosa cells of rats (Fang et al 2012;Wu et al 2011). In addition, T-2 toxin affected the in vitro development of mouse embryos (Somoskoi et al 2014) and induced developmental toxic effects in zebrafish embryos (Yuan et al 2014).…”

Oral administration of fumonisin B1and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

“…It was established that in the rat liver, T-2 toxin inhibits the mitochondrial electron transport system, concluding that mitochondria are possible hepatic targets of T-2 toxin action (27). It is important to add that even in embryonic stem cells (being pluripotent), T-2 toxin induced apoptosis via a reactive oxygen species-mediated mitochondrial pathway (14). In summary, it is proven that T-2 toxin crosses the hepatic cellular and subcellular membranes and disrupts ATP production in mitochondria (28).…”