title: Cadmium-induced autophagy promotes survival of rat cerebral cortical neurons by activating class III phosphoinositide 3-kinase/beclin-1/B-cell lymphoma 2 signaling pathways.
abstract: Autophagy is an evolutionarily conserved response that can be activated in response to heavy metal. Thus, the present study investigated the effect of autophagy on neurotoxic damage caused by cadmium (Cd) in rat cerebral cortical neurons. The results indicated that the viability of cortical neurons treated with Cd was markedly decreased in a dose-and time-dependent manner. The present study provided evidence that cortical neurons treated with Cd underwent autophagy: The conversion of microtubule-associated protein 1A/1B-light chain 3 (LC3) to LC3-II, an increase in the punctate distribution of endogenous LC3-II and the presence of autophagosomes were identified. Combined treatment with Cd and chloroquine, an autophagy inhibitor, reduced the amount of autophagocytosis and cell activity, whereas rapamycin, an autophagy inducer, reduced Cd-mediated cytotoxicity. Furthermore, it was found that beclin-1 and class III phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) were decreased after Cd treatment. LY294002, a specific inhibitor of PI3K, prevented the decline in Bcl-2 production and the increase in levels of beclin-1, class III PI3K and autophagy following Cd treatment. In conclusion, the results of the present study suggested that Cd can induce cytoprotective autophagy by activating the class III PI3K/beclin-1/Bcl-2 signaling pathway, and that the autophagy pathway can serve as a sensitive biomarker for nervous system injury after exposure to Cd.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Kang-Bao
authors.initials: KB
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Cheng-Yang
authors.initials: CY
authors.lastname: Jiang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Hu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Bian
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Xue-Zhong
authors.initials: XZ
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Jian-Hong
authors.initials: JH
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China.
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002738:Chloroquine / Q000633:toxicity; D002867:Chromones / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D002104:Cadmium; D002738:Chloroquine; D002867:Chromones; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one