title: Induction of cytoprotective autophagy in PC-12 cells by cadmium.
abstract: Laboratory data have demonstrated that cadmium (Cd) may induce neuronal apoptosis. However, little is known about the role of autophagy in neurons. In this study, cell viability decreased in a dose- and time-dependent manner after treatment with Cd in PC-12 cells. As cells were exposed to Cd, the levels of LC3-II proteins became elevated, specific punctate distribution of endogenous LC3-II increased, and numerous autophagosomes appeared, which suggest that Cd induced a high level of autophagy. In the late stages of autophagy, an increase in the apoptosis ratio was observed. Likewise, pre-treatment with chloroquine (an autophagic inhibitor) and rapamycin (an autophagic inducer) resulted in an increased and decreased percentage of apoptosis in contrast to other Cd-treated groups, respectively. The results indicate that autophagy delayed apoptosis in Cd-treated PC-12 cells. Furthermore, co-treatment of cells with chloroquine reduced autophagy and cell activity. However, rapamycin had an opposite effect on autophagy and cell activity. Moreover, class III PI3 K/beclin-1/Bcl-2 signaling pathways served a function in Cd-induced autophagy. The findings suggest that Cd can induce cytoprotective autophagy by activating class III PI3 K/beclin-1/Bcl-2 signaling pathways. In sum, this study strongly suggests that autophagy may serve a positive function in the reduction of Cd-induced cytotoxicity.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Wang
authors.forename: Jiaqiao
authors.initials: J
authors.lastname: Zhu
authors.forename: Kangbao
authors.initials: K
authors.lastname: Zhang
authors.forename: Chenyang
authors.initials: C
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D000071186:Beclin-1; D002104:Cadmium / Q000008:administration & dosage*; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D002104:Cadmium; D019869:Phosphatidylinositol 3-Kinases
keywords: Apoptosis; Autophagy; Cadmium; LC3; PC-12 cells