ACTIVATION OF C-JUN N-TERMINAL KINASE STRESS-ACTIVATED PROTEIN-KINASEAND THE DECREASED RATIO OF BCL-2 TO BAX ARE ASSOCIATED WITH THE AUTO-OXIDIZED DOPAMINE-INDUCED APOPTOSIS IN PC12 CELLS

Current concepts of the pathogenesis of Parkinson's disease center on the formation of reactive oxygen species (ROS). Dopamine is one of the major sources of ROS. In this study, the molecular events during the dopamine-induced apoptosis in PC12 cells were studied using auto-oxidi zed dopamine. Auto-oxidized-dopamine induced DNA fragmentation and act ivation of c-jun N-terminal kinase (JNK)/stress-activated protein kina se (SAPK) faster and stronger than dopamine. Furthermore, N-acetylcyst eine, an antioxidant, prevented the auto-oxidized dopamine-induced JNK /SAPK activation and DNA fragmentation. Meanwhile, Bcl-2 started to de crease after onset of apoptosis, and Bar was increased up to beginning of apoptosis, and thereafter decreased. Therefore, these results sugg ested that activation of JNK/SAPK and the decreased ratio of antiapopt otic Bcl-2 to proapoptotic Bar appear to be associated with the dopami ne-induced apoptosis. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.