title: Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken's Tubular Apoptosis Induced by Nickel Chloride (NiCl₂).
abstract: Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl₂) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl₂ in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl₂ inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl₂ also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl₂ causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition.
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. guohonrui@163.com.
authors.forename: Hongrui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. cui580420@sicau.edu.cn.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. cui580420@sicau.edu.cn.
authors.forename: Hengmin
authors.initials: H
authors.lastname: Cui
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. pengxi197313@163.com.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. pengxi197313@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. fangjing4109@163.com.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. fangjing4109@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. zzcjl@126.com.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. zzcjl@126.com.
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. dengjl213@126.com.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. dengjl213@126.com.
authors.forename: Junliang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. wangxun99@163.com.|College of Veterinary Medicine, Sichuan Agricultural University, Ya'an 625014, China. wangxun99@163.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. wubangyuan2008@163.com.
authors.forename: Bangyuan
authors.initials: B
authors.lastname: Wu
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. ckj930@126.com.
authors.forename: Kejie
authors.initials: K
authors.lastname: Chen
authors.affiliation: Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agricultural University, Ya'an 625014, China. dengjl213@126.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002645:Chickens / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009532:Nickel / Q000009:adverse effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C022838:nickel chloride; D009532:Nickel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Bcl-2; NiCl2; PI3K/Akt pathway; apoptosis; mitochondria