The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson‘s Disease

摘要: It is currently believed that excessive oxidant stress induced by metabolism of dopamine (DA), plays a major role in the pathogenesis selective nigrostriatal neuronal loss Parkinson's disease. We recently showed neurotransmitter DA, physiological concentrations, capable initiating apoptosis cultured, post-mitotic sympathetic neurons. Bcl-2 proto-oncogene blocks apoptosis. now report powerful inhibitor DA toxicity PC-12 pheochromocytoma cells. stable expression cells transfection with recombinant pCMV5 vector, containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing manifested marked resistance to otherwise lethal (300 uM) vitroconcentrations DA. This protective effect was reflected trypan-blue test cell survival, 3 H-thymidine incorporation and inhibition characteristic apoptotic morphologic alterations scanning electron microscopic studies. associated control systems may have an important restraining apop-tosis-triggering potential novel field research yield insights into disease lead development therapeutic approaches.