title: Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons.
abstract: The p38 pathway, which is important in mitogen-activated protein kinase (MAPK) family protein signaling, leads to mitochondrial dysfunction and activation of caspase-3. B-cell lymphoma 2 (Bcl‑2) family members are involved in the regulation of activities associated with the survival and death of neurons through apoptosis and have important functions in most types of apoptosis. In the present study, the effects of the p38 MAPK inhibitor SB203580 on N-methyl-d-aspartate (NMDA)-induced cerebral cortical neuron apoptosis were observed to further analyze the possible mechanisms of NMDA-induced neuronal death. Cultured primary cortical neurons were randomly divided into five groups: A control group, NMDA group and three SB203580 interventional groups. The lactate dehydrogenase (LDH) and MTT assays were employed to investigate the effects of the drugs on apoptosis. The morphology of apoptotic cells was observed using acridine orange/ethidium bromide (AO/EB) fluorescence staining. The expression levels of phospho‑(p)‑p38MAPK, Bcl‑2 and Bcl-2-associated X (Bax) were assessed by immunohistochemical methods and western blot analysis to investigate the possible underlying protective mechanisms. The cell viability markedly decreased following incubation with NMDA. The protein levels of cell death repressor Bcl-2 and the levels of Bcl-2/Bax were downregulated. The protein levels of p‑p38MAPK and cell death promoter Bax increased significantly in cells with NMDA treatment. However, these changes were inhibited by SB203580 treatment, particularly in the high‑dose group. Neuronal death induced by NMDA in primary cortical neurons was caused in part by apoptosis, which was mediated through the activation of the p38 signaling pathway by NMDA. SB203580 has neuroprotective effects against NMDA‑induced apoptosis.
authors: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors: Xue-Wen
authors: XW
authors: Liu
authors: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors: En-Fei
authors: EF
authors: Ji
authors: Department of Neurology, Fuxin Central Hospital, Fuxin, Liaoning 123000, P.R. China.
authors: Peng
authors: P
authors: He
authors: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors: Rui-Xian
authors: RX
authors: Xing
authors: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors: Bu-Xian
authors: BX
authors: Tian
authors: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors: Xi-Dong
authors: XD
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D016202:N-Methylaspartate / Q000633:toxicity*; D010766:Phosphorylation; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D051028:bcl-2-Associated X Protein; D016202:N-Methylaspartate; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580