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The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway.
J Trace Elem Med Biol 2015; 29:275-83JT

Abstract

Cadmium (Cd) is an extremely toxic metal capable of severely damaging several organs, including the brain. Studies have shown that Cd induces neuronal apoptosis partially by activating the mitogen-activated protein kinase (MAPK) pathways. However, the underlying mechanism of MAPK involving the mitochondrial apoptotic pathway in neurons remains unclear. In this study, primary rat cerebral cortical neurons were exposed to Cd, which significantly decreased cell viability and the B-cell lymphoma 2/Bcl-2 associate X protein (Bcl-2/Bax) ratio and increased the percentage of apoptotic cells, release of cytochrome c, cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF). In addition, 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, release of cytochrome c, cleavages of caspase-3 and PARP, and nuclear translocation of AIF. Taken together, these data suggest that the ERK- and JNK-mediated mitochondrial apoptotic pathways play important roles in Cd-induced neuronal apoptosis.

Authors+Show Affiliations

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.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.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.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; Bijie Pilot Area Research Institute, Bijie University, Bijie 551700, PR China.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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25043952

Citation

Yuan, Yan, et al. "The Role of Mitogen-activated Protein Kinase in Cadmium-induced Primary Rat Cerebral Cortical Neurons Apoptosis Via a Mitochondrial Apoptotic Pathway." Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), vol. 29, 2015, pp. 275-83.
Yuan Y, Jiang C, Hu F, et al. The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway. J Trace Elem Med Biol. 2015;29:275-83.
Yuan, Y., Jiang, C., Hu, F., Wang, Q., Zhang, K., Wang, Y., ... Liu, Z. (2015). The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway. Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), 29, pp. 275-83. doi:10.1016/j.jtemb.2014.06.006.
Yuan Y, et al. The Role of Mitogen-activated Protein Kinase in Cadmium-induced Primary Rat Cerebral Cortical Neurons Apoptosis Via a Mitochondrial Apoptotic Pathway. J Trace Elem Med Biol. 2015;29:275-83. PubMed PMID: 25043952.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway. AU - Yuan,Yan, AU - Jiang,Chenyang, AU - Hu,Feifei, AU - Wang,Qiwen, AU - Zhang,Kangbao, AU - Wang,Yi, AU - Gu,Jianhong, AU - Liu,Xuezhong, AU - Bian,Jianchun, AU - Liu,Zongping, Y1 - 2014/06/24/ PY - 2014/01/20/received PY - 2014/05/15/revised PY - 2014/06/16/accepted PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2015/8/6/medline KW - Apoptosis KW - Cadmium KW - Mitochondrial apoptotic pathway KW - Mitogen-activated protein kinase KW - Primary rat cerebral cortical neurons SP - 275 EP - 83 JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) JO - J Trace Elem Med Biol VL - 29 N2 - Cadmium (Cd) is an extremely toxic metal capable of severely damaging several organs, including the brain. Studies have shown that Cd induces neuronal apoptosis partially by activating the mitogen-activated protein kinase (MAPK) pathways. However, the underlying mechanism of MAPK involving the mitochondrial apoptotic pathway in neurons remains unclear. In this study, primary rat cerebral cortical neurons were exposed to Cd, which significantly decreased cell viability and the B-cell lymphoma 2/Bcl-2 associate X protein (Bcl-2/Bax) ratio and increased the percentage of apoptotic cells, release of cytochrome c, cleavages of caspase-3 and poly (ADP-ribose) polymerase (PARP), and nuclear translocation of apoptosis-inducing factor (AIF). In addition, 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, release of cytochrome c, cleavages of caspase-3 and PARP, and nuclear translocation of AIF. Taken together, these data suggest that the ERK- and JNK-mediated mitochondrial apoptotic pathways play important roles in Cd-induced neuronal apoptosis. SN - 1878-3252 UR - https://www.unboundmedicine.com/medline/citation/25043952/The_role_of_mitogen_activated_protein_kinase_in_cadmium_induced_primary_rat_cerebral_cortical_neurons_apoptosis_via_a_mitochondrial_apoptotic_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0946-672X(14)00111-4 DB - PRIME DP - Unbound Medicine ER -