The role of NADPH oxidase, neuronal nitric oxide synthase and poly(ADP ribose) polymerase in oxidative neuronal death induced in cortical cultures by brain-derived neurotrophic factor and neurotrophin-4/5

摘要: Certain neurotrophins promote or induce oxidative neuronal death in cortical cultures. However, the effector mechanisms mediating this phenomenon have not been delineated. In study, we investigated possibility that NADPH oxidase and nitric oxide synthase (NOS) function as such effectors. Western blot analysis showed treatment with brain-derived neurotrophic factor (BDNF) neurotrophin (NT)-4/5 increased levels of subunits. Moreover, resulted membrane translocation p67phox, a characteristic feature activation. Administration specific inhibitor, 4-(2-aminoethyl)benzenesulfonylfluoride (AEBSF), attenuated increases oxygen free radicals thereby suggesting contributes to stress induced by neurotrophins. Furthermore, BDNF NT-4/5 was significantly AEBSF. Treatment has previously shown NOS (nNOS). Our data indicated inhibitors nNOS NT-4/5, consistent an active role mediation neurotoxicity. As other models cell death, BDNF-induced accompanied poly(ADP ribose) polymerase (PARP) AEBSF N-nitro-l-arginine (NNA) reduced BDNF-mediated PARP glycohydrolase (PARG) are actively involved neurotoxicity since PARG death. These results suggest contribute stress, subsequent activation PARP/PARG, prolonged exposure.