title: Crosstalk of JNK1-STAT3 is critical for RAW264.7 cell survival.
abstract: T-2 toxin, a major compound of trichothecenes, inhibits protein synthesis and induces inflammation and cell apoptosis through the activation of MAPK pathway. The JAK/STAT pathway has recently been shown to be downstream targets of trichothecenes. However, whether there is any crosstalk between JNK and JAK/STAT pathways in trichothecene toxicity has not been studied. In the present study, we explored this potential in RAW264.7 cells treated with T-2 toxin. Our results revealed a crosstalk between JNK1 and STAT3 after T-2 toxin treatment, which was mediated by K-Ras. T-2 toxin treatment resulted in rapid phosphorylation, and more importantly, JNK1-STAT3 signaling pathway was shown to maintain the normal function of the mitochondria and to inhibit T-2 toxin-induced apoptosis. Therefore, this pathway was considered to be a potential cell survival pathway. Breakdown and degranulation of ribosomes in the rough endoplasmic reticulum and swelling of mitochondria were clearly visible after the cells had been incubated with T-2 toxin for 12h. Our data suggest that T-2 toxin had a Janus face: it induced both apoptotic and cell survival pathways. These results suggest that the crosstalk and the balance between MAPK and JAK/STAT pathway might be involved in T-2 toxin-induced apoptosis in RAW264.7 cells.
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; College of Life Science, Yangtze University, Jingzhou, Hubei 434025, China; Center for Basic and Applied Research, Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, Czech Republic. Electronic address: wqh212@hotmail.com.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wan
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: National Reference Laboratory of Veterinary Drug Residues (HZAU), MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Key Laboratory for Detection of Veterinary Drug Residues, MOA Laboratory of Risk Assessment for Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address: yuan5802@mail.hzau.edu.cn.
authors.forename: Zonghui
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D053612:Janus Kinases / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013605:T-2 Toxin / Q000494:pharmacology; D018631:ras Proteins / Q000378:metabolism
chemical_list: D000873:Anthracenes; D016207:Cytokines; D050796:STAT3 Transcription Factor; C432165:pyrazolanthrone; D053612:Janus Kinases; D048055:Mitogen-Activated Protein Kinase 8; D018631:ras Proteins; D013605:T-2 Toxin
keywords: Cell apoptosis; Cell survival pathway; Crosstalk; JAK/STAT; MAPK; T-2 toxin