title: 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.
authors.affiliation: 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.
authors.forename: Haiqin
authors.initials: H
authors.lastname: Fang
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Jiabin
authors.initials: J
authors.lastname: Guo
authors.forename: Jing
authors.initials: J
authors.lastname: Rong
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.forename: Zengming
authors.initials: Z
authors.lastname: Zhao
authors.forename: Daiying
authors.initials: D
authors.lastname: Zuo
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Peng
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D018920:Coculture Techniques; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D058732:Embryoid Bodies / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013605:T-2 Toxin / Q000494:pharmacology / Q000633:toxicity*; D013723:Teratogens / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D002839:Chromans; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D013723:Teratogens; D045304:Cytochromes c; D013605:T-2 Toxin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid