Nickel chloride (NiCl2) in hepatic toxicity: apoptosis, G2/M cell cycle arrest and inflammatory response.
Up to now, the precise mechanism of Ni toxicology is still indistinct. Our aim was to test the apoptosis, cell cycle arrest and inflammatory response mechanism induced by NiCl2in the liver of broiler chickens. NiCl2significantly increased hepatic apoptosis. NiCl2activated mitochondria-mediated apoptotic pathway by decreasing Bcl-2, Bcl-xL, Mcl-1, and increasing Bax, Bak, caspase-3, caspase-9 and PARP mRNA expression. In the Fas-mediated apoptotic pathway, mRNA expression levels of Fas, FasL, caspase-8 were increased. Also,NiCl2induced ER stress apoptotic pathway by increasing GRP78 and GRP94 mRNA expressions. The ER stress was activated through PERK, IRE1 and ATF6 pathways, which were characterized by increasing eIF2α, ATF4, IRE1, XBP1 and ATF6 mRNA expressions. And, NiCl2arrested G2/M phase cell cycle by increasing p53, p21 and decreasing cdc2, cyclin B mRNA expressions. Simultaneously, NiCl2increased TNF-α, IL-1β, IL-6, IL-8 mRNA expressions through NF-κB activation. In conclusion, NiCl2induces apoptosis through mitochondria, Fas and ER stress-mediated apoptotic pathways and causes cell cycle G2/M phase arrest via p53-dependent pathway and generates inflammatory response by activating NF-κB pathway.
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.
Hongrui
H
Guo
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Hengmin
H
Cui
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Jing
J
Fang
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Zhicai
Z
Zuo
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Junliang
J
Deng
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Xun
X
Wang
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.|Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University Ya'an 625014, China.
Ling
L
Zhao
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.
Kejie
K
Chen
College of Veterinary Medicine, Sichuan Agricultural University Ya'an 625014, China.
Jie
J
Deng
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; C022838:nickel chloride; D009532:Nickel
NiCl2; apoptosis; cell cycle G2/M phase arrest; inflammatory response; liver