Document Detail


The effect of endogenous dopamine in rotenone-induced toxicity in PC12 cells.
MedLine Citation:
PMID:  15890007     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deficiencies in Complex I have been observed in Parkinson's disease (PD) patients. Systemic exposure to rotenone, a Complex I inhibitor, has been shown to lead to selective dopaminergic cell death in vivo and toxicity in many in vitro models, including dopaminergic cell cultures. However, it remains unclear why rotenone seems to affect dopaminergic cells more adversely. Therefore, the role of dopamine (DA) in rotenone-induced PC12 cell toxicity was examined. Rotenone (1.0 muM) caused significant toxicity in differentiated PC12 cells, which was accompanied by decreases in ATP levels, changes in catechol levels, and increased DA oxidation. To determine whether endogenous DA makes PC12 cells more susceptible to rotenone, cells were treated with the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT) to reduce DA levels prior to rotenone exposure, and then cell viability was measured. No changes in rotenone-induced toxicity were observed with or without AMPT treatment. However, a potentiation of toxicity was observed following coexposure of PC12 cells to rotenone and methamphetamine. To determine whether this effect was due to DA, PC12 cells were depleted of DA prior to methamphetamine and rotenone cotreatment, resulting in a large attenuation in toxicity. These findings suggest that DA plays a role in rotenone-induced toxicity and possibly the vulnerability of DA neurons in PD.
Authors:
April A Dukes; Kimberly M Korwek; Teresa G Hastings
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  7     ISSN:  1523-0864     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:    2005 May-Jun
Date Detail:
Created Date:  2005-05-13     Completed Date:  2005-09-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  630-8     Citation Subset:  IM    
Affiliation:
Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Catechols / metabolism
Cell Survival / drug effects
Dopamine / metabolism*
Enzyme Inhibitors / pharmacology
Methamphetamine / metabolism
Oxidation-Reduction / drug effects
PC12 Cells
Rats
Rotenone / toxicity*
Tyrosine 3-Monooxygenase / antagonists & inhibitors,  metabolism
alpha-Methyltyrosine / pharmacology
Grant Support
ID/Acronym/Agency:
DA09601/DA/NIDA NIH HHS; NS44076/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Catechols; 0/Enzyme Inhibitors; 120-80-9/catechol; 537-46-2/Methamphetamine; 56-65-5/Adenosine Triphosphate; 658-48-0/alpha-Methyltyrosine; 83-79-4/Rotenone; EC 1.14.16.2/Tyrosine 3-Monooxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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