title: Mycotoxin zearalenone induces apoptosis in mouse Leydig cells via an endoplasmic reticulum stress-dependent signalling pathway.
abstract: Zearalenone (ZEN) is a Fusarium mycotoxin that causes several reproductive disorders and genotoxic effects. This study demonstrated the involvement of endoplasmic reticulum (ER) stress in ZEN-induced mouse Leydig cell death. Our study showed that ZEN reduced cell proliferation in a murine Leydig tumour cell line in a dose-dependent manner. The involvement of apoptosis as a major cause of ZEN-induced cell death was further confirmed by the results of a caspase-3 activity assay, which showed a ZEN dose-dependent increase in cell death. Treatment of MLTC-1 and primary mouse Leydig cells with ZEN upregulated the expression of the ER stress-typical markers GRP78, CHOP and caspase-12 protein. Further, pre-treating the cells with 4-phenylbutyrate or knocking down GRP78 using lentivirus-encoded shRNA significantly diminished ZEN-induced apoptosis and inhibited the expression of CHOP and caspase-12. In summary, these results suggest that the activation of an ER stress pathway plays a key role in ZEN-induced apoptosis in the mouse Leydig cells.
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: linpengfei@nwsuaf.edu.cn.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: cfl0604114114@163.com.
authors.forename: Fenglei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: 270481554@qq.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: 1369862354@qq.com.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: xiangguo731@163.com.
authors.forename: Xiangguo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: pipixiaoguai0118@163.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: Lixiao615@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: 992565978@qq.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: aihuawang1966@163.com.
authors.forename: Aihua
authors.initials: A
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, China; College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: yapingjin@163.com.
authors.forename: YaPing
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D007985:Leydig Cells / Q000187:drug effects* / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D010654:Phenylbutyrates / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013739:Testosterone / Q000096:biosynthesis; D015025:Zearalenone / Q000494:pharmacology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D010654:Phenylbutyrates; D034741:RNA, Small Interfering; D013739:Testosterone; D015025:Zearalenone; C075773:4-phenylbutyric acid; D053148:Caspase 3
keywords: Apoptosis; Endoplasmic reticulum stress; Murine Leydig tumour cell line; Primary mouse Leydig cells; Zearalenone