title: Nitric oxide (NO)-mediated mitochondrial damage plays a critical role in T-2 toxin-induced apoptosis and growth hormone deficiency in rat anterior pituitary GH3 cells.
abstract: 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.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
authors.forename: Xianglian
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Guo
authors.affiliation: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Wuhan, China.
authors.forename: Aimei
authors.initials: A
authors.lastname: Liu
authors.affiliation: College of Life Science, Yangtze University, Jingzhou, China; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Czechia.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
authors.forename: Xijuan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
authors.forename: Menghong
authors.initials: M
authors.lastname: Dai
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
authors.forename: Haihong
authors.initials: H
authors.lastname: Hao
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.affiliation: Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Xie
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, China. Electronic address: wangxu@mail.hzau.edu.cn.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D013006:Growth Hormone / Q000172:deficiency*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010903:Pituitary Gland, Anterior / Q000166:cytology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D052683:Somatotrophs / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013605:T-2 Toxin / Q000633:toxicity*
chemical_list: D009569:Nitric Oxide; D013006:Growth Hormone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D020169:Caspases; D013605:T-2 Toxin
keywords: Caspase pathway; Cell apoptosis; Growth hormone deficiency; Mitochondrial damage; NO; T-2 toxin