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

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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.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (81172699), National Key Project on Drug Development from the Ministry of Science and Technology of China (2009ZX09501-034) and International cooperation projects from Ministry of Science and Technology of China (2008DFB300090 and 2011DFA32190).

Conflict of interest

The authors state no duality of interest.

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Authors and Affiliations

  1. Evaluation and Research Centre for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing, 100071, People’s Republic of China

    Haiqin Fang, Jiabin Guo, Jing Rong, Long Ma, Zengming Zhao & Shuangqing Peng

  2. Department of Pharmacology, College of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Haiqin Fang, Yingliang Wu & Daiying Zuo

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  1. Haiqin Fang
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  2. Yingliang Wu
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Correspondence to Shuangqing Peng.

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Fang, H., Wu, Y., Guo, J. et al. T-2 toxin induces apoptosis in differentiated murine embryonic stem cells through reactive oxygen species-mediated mitochondrial pathway. Apoptosis 17, 895–907 (2012). https://doi.org/10.1007/s10495-012-0724-3

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