Document Detail


Dopamine-induced apoptosis is inhibited in PC12 cells expressing Bcl-2.
MedLine Citation:
PMID:  9187486     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Degeneration of nigrostriatal dopaminergic neurons is the major pathogenic substrate of Parkinson's disease (PD). It is assumed that the lethal trigger is the accumulation of oxidative reactive species generated during metabolism of the natural neurotransmitter dopamine. 2. We have recently shown that dopamine is capable of inducing programmed cell death (PCD) or apoptosis in cultured postmitotic chick sympathetic neurons and rat PC12 pheochromocytoma cells. 3. The bcl-2 gene encodes a protein which blocks physiological PCD in many mammalian cells. In an attempt to elucidate further the mechanism of dopamine toxicity, we examined the potential protective effect of bcl-2 in PC12 cells which were transfected with the protooncogene. 4. In our experiments, Bcl-2 producing cells showed a marked resistance to dopamine toxicity. The percentage of nuclear condensation and DNA fragmentation visualized by the end-labeling method following dopamine treatment was significantly lower in bcl-2 expressing cells. Bcl-2 did not protect PC12 cells against toxicity induced by exposure to dopamine-melanin. Extracts of PC12 cells containing Bcl-2 inhibited dopamine autooxidation and formation of dopamine-melanin. Furthermore, the presence of Bcl-2 protected cells from thiol imbalance and prevented thiol loss following exposure to dopamine. 5. The protective effects of Bcl-2 against dopamine toxicity may be explained, in part, by its action as an antioxidant and by its interference in the production of toxic agents. The possible protection by Bcl-2 against neuronal degeneration caused by dopamine may play a role in the pathogenesis of PD and may provide a new direction for the development of neuroprotective therapies.
Authors:
D Offen; I Ziv; H Panet; L Wasserman; R Stein; E Melamed; A Barzilai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular and molecular neurobiology     Volume:  17     ISSN:  0272-4340     ISO Abbreviation:  Cell. Mol. Neurobiol.     Publication Date:  1997 Jun 
Date Detail:
Created Date:  1997-07-30     Completed Date:  1997-07-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8200709     Medline TA:  Cell Mol Neurobiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  289-304     Citation Subset:  IM    
Affiliation:
Department of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology
Apoptosis / drug effects*,  genetics,  physiology
Cell Extracts / physiology
Cell Survival
Culture Media, Serum-Free
DNA Damage / drug effects
Dopamine / toxicity*
In Situ Hybridization
Melanins / metabolism,  toxicity
Mice
PC12 Cells / drug effects,  physiology
Proto-Oncogene Proteins c-bcl-2 / biosynthesis*,  physiology
Rats
Sulfhydryl Compounds / metabolism
Thymidine / metabolism,  pharmacokinetics
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cell Extracts; 0/Culture Media, Serum-Free; 0/Melanins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Sulfhydryl Compounds; 50-89-5/Thymidine

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