Liu Xianglian, Guo Pu, Liu Aimei, Wu Qinghua, Xue Xijuan, Dai Menghong, Hao Haihong, Qu Wei, Xie Shuyu, Wang Xu, Yuan Zonghui
National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
Food Chem Toxicol. 2017 Apr;102:11-23. doi: 10.1016/j.fct.2017.01.017. Epub 2017 Jan 24.
T-2 toxin, a major compound of trichothecenes, induces cell apoptosis and growth hormone (GH) deficiency and causes considerable growth retardation in animals and human cells. However, the mechanism underlying its growth suppression still remains unclear. Recent studies have suggested that ROS induced cell apoptosis and animal feed intake reduction, but there are limited reports on the role of RNS in T-2 toxin-mediated mitochondrial damage, cell apoptosis and growth retardation. Herein, T-2 toxin-induced GH3 cell damage and apoptosis were tested by MTT assay, LDH leakage and flow cytometry, respectively. Intracellular NO and antioxidant enzyme activity, ΔΨm, morphometric changes of mitochondria, the caspase pathway, and inflammatory factors were investigated. Free radical scavengers NAC, SOD and NO scavenger haemoglobin were used to explore the role of oxidative stress and the relationship between NO production and caspase pathway. The results clearly revealed that T-2 toxin caused significant increases in NO generation, cell apoptosis, GH deficiency, increased iNOS activity, upregulation of inflammatory factors and caspase pathway, decreases in ΔΨm and morphosis damage. These data suggest that mitochondria are a primary target of T-2 toxin-induced NO, and NO is a key mediator of T-2 toxin-induced cell apoptosis and GH deficiency via the mitochondria-dependent pathway in cells.
T-2毒素是单端孢霉烯族化合物的主要成分，可诱导细胞凋亡和生长激素（GH）缺乏，并导致动物和人类细胞出现明显的生长迟缓。然而，其生长抑制的潜在机制仍不清楚。最近的研究表明，活性氧（ROS）可诱导细胞凋亡和动物采食量减少，但关于活性氮（RNS）在T-2毒素介导的线粒体损伤、细胞凋亡和生长迟缓中的作用报道有限。在此，分别通过MTT法、乳酸脱氢酶（LDH）泄漏检测和流式细胞术检测T-2毒素诱导的GH3细胞损伤和凋亡。研究了细胞内一氧化氮（NO）和抗氧化酶活性、线粒体膜电位（ΔΨm）、线粒体形态变化、半胱天冬酶途径和炎症因子。使用自由基清除剂N-乙酰半胱氨酸（NAC）、超氧化物歧化酶（SOD）和NO清除剂血红蛋白来探讨氧化应激的作用以及NO产生与半胱天冬酶途径之间的关系。结果清楚地表明，T-2毒素导致NO生成显著增加、细胞凋亡、GH缺乏、诱导型一氧化氮合酶（iNOS）活性增加、炎症因子上调和半胱天冬酶途径激活、ΔΨm降低以及形态损伤。这些数据表明，线粒体是T-2毒素诱导产生NO的主要靶点，并且NO是T-2毒素通过细胞内线粒体依赖性途径诱导细胞凋亡和GH缺乏的关键介质。
