Document Detail


The proto-oncogene Bcl-2 inhibits cellular toxicity of dopamine: possible implications for Parkinson's disease.
MedLine Citation:
PMID:  14646549     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
It is currently believed that excessive oxidant stress induced by metabolism of dopamine (DA), plays a major role in the pathogenesis of the selective nigrostriatal neuronal loss in Parkinson's disease. We recently showed that the neurotransmitter DA, in physiological concentrations, is capable of initiating apoptosis in cultured, post-mitotic sympathetic neurons. Bcl-2 is a proto-oncogene that blocks apoptosis. We now report that Bcl-2 is a powerful inhibitor of DA toxicity in PC-12 pheochromocytoma cells. We induced stable expression of Bcl-2 in PC-12 cells by transfection with recombinant pCMV5 expression vector, containing mouse bcl-2 (coding-sequence) cDNA. Cells expressing Bcl-2 manifested marked resistance to otherwise lethal (300 uM) in vitroconcentrations of DA. This protective effect was reflected in the trypan-blue test of cell survival, 3 H-thymidine incorporation and inhibition of the characteristic apoptotic morphologic alterations in scanning electron microscopic studies. Bcl-2 and associated control systems of apoptosis may have an important physiological role in restraining the apop-tosis-triggering potential of DA in nigrostriatal neurons. This novel field of research may yield insights into the pathogenesis of Parkinson's disease and lead to development of novel therapeutic approaches.
Authors:
I Ziv; D Offen; R Haviv; R Stein; H Panet; R Zilkha-Falb; A Shirvan; A Barzilai; E Melamed
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  2     ISSN:  1360-8185     ISO Abbreviation:  Apoptosis     Publication Date:  1997  
Date Detail:
Created Date:  2003-12-03     Completed Date:  2003-12-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  149-55     Citation Subset:  -    
Affiliation:
Department of Neurology and the Felsenstein Medical Research Center, Petah-Tiqva, Israel.
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