The role of mitogen-activated protein kinase in cadmium-induced primary rat cerebral cortical neurons apoptosis via a mitochondrial apoptotic pathway |
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| Institution: | 1. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, PR China;2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, PR China;3. Bijie Pilot Area Research Institute, Bijie University, Bijie 551700, PR China;1. State Key Lab of Food Science and Technology, Nanchang University, Nanchang 330047, China;2. Nanoscale Science and Technology Laboratory, Institute for Advanced Study, Nanchang University, Nanchang 330031, China;3. Chuanqi Pharmaceutical Corp. Ltd, Jiangxi Povince, Nanchang 330047, China;1. Health & Safety Laboratory, Buxton SK17 9JN, UK;2. BASF Performance Products Plc, Bradford BD12 OJZ, UK;1. Department of Clinical, Toxicological and Bromatological Analysis, Faculty of Pharmaceutical Sciences of University of São Paulo – USP, Ribeirao Preto, SP, Brazil;2. Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil;3. Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil;4. Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil;5. Department of Pharmacology, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil;6. Center for Toxicological Assistance – CEATOX, Institute of Biosciences, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil;1. Chemical Synthesis Department, Center for Genetic Engineering and Biotechnology, Havana, Cuba;2. Departament de Ciències Experimentals i de la Salut, UPF/PRBB, Barcelona, Spain;3. Mass Spectrometry Department, Center for Molecular Immunology, Havana, Cuba;4. Mass Spectrometry Laboratory, Proteomics Department, CIGB, Havana, Cuba;5. Quality Assurance Unit, CIGB, Havana, Cuba;6. Pharmaceutical Research Division, CIGB, Havana, Cuba;1. Institut für Tierernährung, Ernährungsschäden und Diätetik, Veterinärmedizinische Fakultät, Universität Leipzig, An den Tierkliniken 9, D-04103 Leipzig, Germany;2. Institut für Agrar- und Ernährungswissenschaften, Abteilung Präventive Ernährung, Martin-Luther-Universität Halle-Wittenberg, von Danckelmann-Platz 2, D-06120 Halle/Salle, Germany;3. Institut für Tierernährung und Ernährungsphysiologie, Justus-Liebig-Universität-Universität Giessen, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany;1. UNAM-Institute of Materials Science & Nanotechnology, Bilkent University, Ankara 06800, Turkey;2. Gazi University Life Sciences Application and Research Center, Ankara 06830, Turkey;3. Gazi University, Department of Medical Biology and Genetics, Faculty of Medicine, 06500, Besevler, Ankara, Turkey |
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| 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. |
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| Keywords: | Cadmium Apoptosis Mitochondrial apoptotic pathway Mitogen-activated protein kinase Primary rat cerebral cortical neurons |
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