{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:59:29Z","timestamp":1783576769074,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T00:00:00Z","timestamp":1442966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u02b9-deoxyuridine 5\u02b9-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.<\/jats:p>","DOI":"10.3390\/ijms160922989","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T12:24:25Z","timestamp":1443011065000},"page":"22989-23011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Modulation of the PI3K\/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken\u2019s Tubular Apoptosis Induced by  Nickel Chloride (NiCl2)"],"prefix":"10.3390","volume":"16","author":[{"given":"Hongrui","family":"Guo","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-531X","authenticated-orcid":false,"given":"Hengmin","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhicai","family":"Zuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"},{"name":"College of Veterinary Medicine, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kejie","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province,  Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,9,23]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Nickel as an essential element and a toxicant","volume":"1","author":"Poonkothai","year":"2012","journal-title":"Int. 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