title: Induction of mitochondria-mediated apoptosis and PI3K/Akt/ mTOR-mediated autophagy by aflatoxin B2 in hepatocytes of broilers.
abstract: Aflatoxins have been shown to induce hepatotoxicity in animal models, but the effects of aflatoxin B2 (AFB2) on broiler hepatocytes is unclear. This study aimed to investigate the effects of AFB2 on apoptosis and autophagy to provide an experimental basis for understanding the mechanism of aflatoxin-induced hepatotoxicity. One hundred-twenty Cobb500 broilers were allocated to four groups and exposed to 0 mg/kg, 0.2 mg/kg, 0.4 mg/kg, and 0.8 mg/kg of AFB2 per day for 21 d. AFB2 exerted potent proapoptotic and proautophagic effects on hepatocytes, with increased numbers of apoptotic and autophagic hepatocytes.Poly ADP-ribose polymerase (PARP) was cleaved and caspase-3 was activated in experimental groups, showing that the apoptosis of hepatocytes was triggered by AFB2. Increased levels of the autophagy factors Beclin-1 and LC3-II/LC3-I, as well as down-regulation of p62, a marker of autophagic flux, provided additional evidence for AFB2-triggered autophagy. AFB2 induced mitochondria-mediated apoptosis via the production of reactive oxygen species (ROS) and promotion of the translocation of Bax and cytochrome c (cyt c) between mitochondria and the cytosol, triggering the formation of apoptosomes. AFB2 also inhibited the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway by activating PI3K, Akt, and mTOR and inhibiting their phosphorylation, contributing to the proautophagic activity of AFB2. These findings provide new insights into the mechanisms involved in AFB2-induced hepatotoxicity in broilers.
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Binlong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Diyan
authors.initials: D
authors.lastname: Li
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Sichen
authors.initials: S
authors.lastname: Li
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Kenan
authors.initials: K
authors.lastname: Peng
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Xian
authors.initials: X
authors.lastname: Shi
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Lanyun
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Zhongxian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Huadong
authors.initials: H
authors.lastname: Yin
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, P.R.China, 611130.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D030161:Avian Proteins / Q000378:metabolism; D000071186:Beclin-1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens; D022781:Hepatocytes / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D000348:Aflatoxins; D030161:Avian Proteins; D000071186:Beclin-1; D008869:Microtubule-Associated Proteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; C029753:aflatoxin B2; D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: PI3K/Akt/mTOR-mediated autophagy; aflatoxin B2; broiler; hepatocytes; mitochondria-mediated apoptosis