Involvement of mitogen-activated protein kinase pathways in N-methyl-D-aspartate-induced excitotoxic

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Previous studies have shown that mitogen-activated protein kinase(MAPK) signaling pathways are involved in N-methyl-D-aspartate(NMDA)-mediated excitotoxicity.However,a systematic observation or analysis of the role of these various MAPK pathways in excitotoxicity processes does not exist.The present study further evaluated the role and contribution of three MAPK pathways extracellular signal-regulated kinase,c-Jun N-terminal kinase,and p38 MAPK in an NMDA-mediated excitotoxicity model using MAPK-specific inhibitor.Results demonstrated that c-Jun N-terminal kinase inhibitor SP600125 and/or p38 MAPK inhibitor SB203580 inhibited NMDA-induced reduction in cell viability,as well as reduced NMDA-induced lactate dehydrogenase leakage and reactive oxygen species production.However,PD98059,an inhibitor of extracellular signal-regulated kinase,did not influence this model.Results demonstrated an involvement of c-Jun N-terminal kinase and p38 MAPK,but not extracellular signal-regulated kinase,in NMDA-mediated excitotoxicity in cortical neurons. Previous studies have shown that mitogen-activated protein kinase (MAPK) signaling pathways are involved in N-methyl-D-aspartate (NMDA) -mediated excitotoxicity. However, a systematic observation or analysis of the role of these various MAPK pathways in excitotoxicity processes does not exist. The present study further evaluated the role and contribution of three MAPK pathways extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 MAPK in an NMDA-mediated excitotoxicity model using MAPK- c-Jun N-terminal kinase inhibitor SB203580 inhibited NMDA-induced reduction in cell viability, as well as reduced NMDA-induced lactate dehydrogenase leakage and reactive oxygen species production. However, PD98059, an inhibitor of extracellular signal -regulated kinase, did not affect this model. Resulting from an involvement of c-Jun N-terminal kinase and p38 MAPK, but not extracellular signal-regulated kinase, in NMDA-mediated excitotoxicity in cortical neurons.
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