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

Abstract

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-κB) was observed in dopaminergic neurons of patient with PD. However, its role is not known. The present study examined the possible role of NF-κB 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-κB. Suppression of the transcriptional activity of NF-κB in PC12 cells by overexpression of a wild-type and a dominant negative mutant form (S32A/S36A) of inhibitor kappa B (lκB)-α led to increase of apoptotic cell death induced by treatment of ODA. In addition, overexpression of NF-κB in PC12 cells blocked ODA-induced cell death. However, JNK/SAPK activities, which mediate various stress signals, were similar among the parentat, NF-κB- or dominant negative mutant IκBα-transfected cells. Therefore, these results suggest that activation of NF-κB 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.