title: Cadmium induced inhibition of autophagy is associated with microtubule disruption and mitochondrial dysfunction in primary rat cerebral cortical neurons.
abstract: Recent studies have reported that mitochondria serve as direct targets for cadmium- (Cd-) induced neuronal toxicity, which can be attenuated by autophagy. The molecular mechanisms' underlying Cd-induced mitochondrial dysfunction and autophagy in neurons are not known. In this study, we studied the upstream signaling pathways induced by Cd-mediated mitochondrial metabolism alterations using primary rat neuron as a model. We found that Cd induced the destruction of microtubules (MTs), and resulted in tau hyper-phosphorylation and decreased acetylated tubulin levels, which were related to a decrease in mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. As a result of taxol disruption, alterations in macroautophagy, like altered cellular distribution of the autophagy-related protein light chain 3 beta (LC3B) and the expression of Atg5 were found compared with Cd group. We found for the first time that MT disruption induced by Cd reduced the levels of autophagy, leading to mitochondrial dysfunction. These observations suggest new therapeutic strategies aimed to activate or ameliorate pro-survival macroautophagy.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Ruilong
authors.initials: R
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China.
authors.forename: Jiaqiao
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China. Electronic address: liuzongping@yzu.edu.cn.
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000199:Actins; D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D002104:Cadmium; D008869:Microtubule-Associated Proteins; D015739:Nocodazole; D017239:Paclitaxel; D017382:Reactive Oxygen Species; D050257:Tubulin Modulators; C526109:Anxa3 protein, rat
keywords: Autophagy; Cadmium; Microtubules; Mitochondria; Neuronal toxicity