期刊
TOXICOLOGY LETTERS
卷 202, 期 3, 页码 168-177出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2011.01.029
关键词
T-2 toxin; Apoptosis; Reactive oxygen species; Mitochondrial; Granulosa cells
类别
资金
- Ministry of Science and Technology of China [2009ZX09501-027, 2009ZX09501-034]
Objective: To investigate the reproductive toxicity and cytotoxicity of T-2 toxin, which is a mycotoxin, and to explore its potential apoptotic induction mechanism. Methods: Ovarian granulosa cells of rats were treated with T-2 toxin (1-100 nM) for 24 h. The cytotoxicity was assessed with MTT bioassay; apoptotic cells were identified microscopically by chromatin condensation and nuclear fragmentation with Hoechst 33258; mitochondrial membrane potential with hodamine 123 and reactive reactive oxygen species (ROS) with 2',7'-dichlorofluoresceinacetate (DCFH-DA) was analyzed by fluorometry; p53 and other apoptosis-related proteins such as Bax, Bcl-2, caspase-3, caspase-9 were determined by Western blot analysis, and related mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). The caspase activity was measured by cleavage of the caspase substrate (Ac-DEVD-pNA for caspase-3. Ac-LEHD- pNA for caspase-9). Results: T-2 toxin inhibited the growth of granulosa cells in a concentration-dependent way. The result of Hoechst 33258 staining indicated that T-2 toxin induces granulosa cells apoptosis based on the typical apoptotic morphological changes. Subsequently, we found that T-2 toxin treatment induced ROS accumulation in granulosa cells, resulting in reduction of mitochondrial transmembrane potential. The induction of cell apoptosis was caused by the upregulation of p53, Bax, Bcl-2, Bax/Bcl-2 ration, and the activation of the caspases pathways. T-2 toxin-induced apoptotic granulosa cells significantly decreased through the use of antioxidant Trolox. Conclusion: These data suggest a possible underlying molecular mechanism for T-2 toxin that induces the apoptosis signaling pathway in rat granulosa cells by regulation of ROS-mediated mitochondrial pathway. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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