| 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 |
Related Documents
:
|
8782646 - Down-regulation of apoptosis-related bcl-2 but not bcl-xl or bax proteins in multidrug-... 7981146 - Disregulation of myc expression in murine bone marrow cells results in an inability to ... 9688306 - Delivery to cancer cells of antisense l-myc oligonucleotides incorporated in fusogenic,... 18785266 - Simultaneous evaluation of viability and bcl-2 in small-cell lung cancer. 22920036 - Mapping single-cell-substrate interactions by surface plasmon resonance microscopy. 10966436 - Lactococcus lactis as a cell factory for high-level diacetyl production. |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of inorganic mercury and methylmercury on the ionic currents of cultured rat hippocampal neu...
Next Document: Lead reduces depolarization-induced calcium entry in cultured DRG neurons without crossing the cell ...