title: Nickel chloride (NiCl2) induces endoplasmic reticulum (ER) stress by activating UPR pathways in the kidney of broiler chickens.
abstract: It has been known that overexposure to Ni can induce nephrotoxicity. However, the mechanisms of underlying Ni nephrotoxicity are still elusive, and also Ni- and Ni compound-induced ER stress has been not reported in vivo at present. Our aim was to use broiler chickens as animal model to test whether the ER stress was induced and UPR was activated by NiCl2 in the kidney using histopathology, immunohistochemistry and qRT-PCR. Two hundred and eighty one-day-old broiler chickens were divided into 4 groups and fed on a control diet and the same basal diet supplemented with 300 mg/kg, 600mg/kg and 900mg/kg of NiCl2 for 42 days. We found that dietary NiCl2 in excess of 300 mg/kg induced ER stress, which was characterized by increasing protein and mRNA expression of ER stress markers, e.g., GRP78 and GRP94. Concurrently, all the three UPR pathways were activated by dietary NiCl2. Firstly, the PERK pathway was activated by increasing eIF2a and ATF4 mRNA expression. Secondly, the IRE1 pathway was activated duo to increase in IRE1 and XBP1 mRNA expression. And thirdly, the increase of ATF6 mRNA expression suggested that ATF6 pathway was activated. The findings clearly demonstrate that NiCl2 induces the ER stress through activating PERK, IRE1 and ATF6 UPR pathways, which is proved to be a kind of molecular mechanism of Ni- or/and Ni compound-induced nephrotoxicity.
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Hengmin
authors.initials: H
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Junliang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.|College of Veterinary Medicine, Sichuan Agricultural University, Yaan, Sichuan, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.
authors.forename: Bangyuan
authors.initials: B
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.
authors.forename: Kejie
authors.initials: K
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Yaan, Sichuan, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000096:biosynthesis / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009532:Nickel / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000187:drug effects*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C018551:glucose-regulated proteins; D051701:Activating Transcription Factor 4; C022838:nickel chloride; D009532:Nickel
keywords: ER stress; IRE1; Immune response; Immunity; Immunology and Microbiology Section; NiCl2; PERK; UPR