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Cadmiuminduced autophagy promotes survival of rat cerebral cortical neurons by activating class III phosphoinositide 3kinase/beclin1/Bcell lymphoma 2 signaling pathways

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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 timedependent manner. The present study provided evidence that cortical neurons treated with Cd underwent autophagy: The conversion of microtubuleassociated protein 1A/1Blight chain 3 (LC3) to LC3II, an increase in the punctate distribution of endogenous LC3II 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 Cdmediated cytotoxicity. Furthermore, it was found that beclin1 and class III phosphoinositide 3 kinase (PI3K) levels were increased, while levels of the antiapoptotic protein Bcell lymphoma 2 (Bcl2) were decreased after Cd treatment. LY294002, a specific inhibitor of PI3K, prevented the decline in Bcl2 production and the increase in levels of beclin1, 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/beclin1/Bcl2 signaling pathway, and that the autophagy pathway can serve as a sensitive biomarker for nervous system injury after exposure to Cd.
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Document Type: Research Article

Affiliations: College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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