title: Cadmium induces PC12 cells apoptosis via an extracellular signal-regulated kinase and c-Jun N-terminal kinase-mediated mitochondrial apoptotic pathway.
abstract: To investigate the role of mitogen-activated protein kinase (MAPK) and downstream events in cadmium (Cd)-induced neuronal apoptosis executed via the mitochondrial apoptotic pathway, this study used the PC-12 cell line as a neuronal model. The result showed that Cd significantly decreased cell viability and the Bcl-2 / Bax ratio and increased the percentage of apoptotic cells, release of cytochrome c, caspase-3, and poly(ADP-ribose) polymerase cleavage, and nuclear translocation of apoptosis-inducing factor (AIF) and endonuclease G. In addition, exposure to Cd-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Inhibition of ERK and JNK, but not p38 MAPK, partially protected the cells from Cd-induced apoptosis. ERK and JNK inhibition also blocked alteration of the Bcl-2 / Bax ratio and cytochrome c release and suppressed caspase-3 and poly(ADP-ribose) polymerase cleavage and AIF and endonuclease G nuclear translocation. Taken together, these data suggest that the ERK- and JNK-mediated mitochondrial apoptotic pathway played an important role in Cd-induced PC12 cells apoptosis.
authors.affiliation: College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, People's Republic of China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Feifei
authors.initials: F
authors.lastname: Hu
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Wang
authors.forename: Kangbao
authors.initials: K
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianhong
authors.initials: J
authors.lastname: Gu
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Liu
authors.forename: Jianchun
authors.initials: J
authors.lastname: Bian
authors.forename: Zongping
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002104:Cadmium; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases