Antiapoptotic role of NF-kappaB in the auto-oxidized dopamine-induced apoptosis of PC12 cells.

Current concepts of the pathogenesis of Parkinson's disease (PD) center on the formation of reactive oxygen species (ROS), and dopamine has been considered to be a major source of ROS. Recently, it has been shown in a postmortem study that nuclear translocation of nuclear factor-kappa B (NF-kappaB) was observed in dopaminergic neurons of patient with PD. However, its role is not known. The present study examined the possible role of NF-kappaB in ODA (auto-oxidized dopamine)-induced apoptosis to understand the process of PD. Using the electrophoretic mobility shift assay, it was found that ODA activated the DNA binding activity of NF-kappaB. Suppression of the transcriptional activity of NF-kappaB in PC12 cells by overexpression of a wild-type and a dominant negative mutant form (S32A/S36A) of inhibitor kappa B (IkappaB)-alpha led to increase of apoptotic cell death induced by treatment of ODA. In addition, overexpression of NF-kappaB in PC12 cells blocked ODA-induced cell death. However, JNK/SAPK activities, which mediate various stress signals, were similar among the parental, NF-kappaB- or dominant negative mutant IkappaB alpha-transfected cells. Therefore, these results suggest that activation of NF-kappaB during ODA-induced apoptosis may have a counteracting activity against the signals mediating apoptotic cell death and thereby delay the process of Parkinson's disease.