Document Detail

Intracellular dopamine oxidation mediates rotenone-induced apoptosis in PC12 cells.
MedLine Citation:
PMID:  15659109     Owner:  NLM     Status:  MEDLINE    
AIM: To study the role of dopamine (DA) in rotenone-induced neurotoxicity in PC12 cells. METHODS: Cell viability was assessed by detecting the leakage of lactate dehydrogenase (LDH) into the medium. Apoptosis rate was measured by flow cytometry. Caspase-3-like activity was measured by fluorescence assay using the probe Ac-DEVD-AMC. The level of intracellular hydrogen peroxide and other peroxides in PC12 cells were quantified by loading cells with 2'-7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) in fluorescence assay. Lactic acid was measured spectrophotometrically. The DA levels in PC12 cells were determined by HPLC-ECD. RESULTS: A 48-h incubation of PC12 cells with rotenone caused an apoptotic cell death and elevated intracellular reactive oxygen species (ROS) and lactic acid accumulation. Intracellular DA depletion with reserpine significantly attenuated rotenone-induced ROS accumulation and apoptotic cell death. No change was found in rotenone-induced ROS accumulation when cells were co-treated with deprenyl. Brief treatment with reserpine at the end of rotenone treatment had no effect on rotenone-induced neurotoxicity. However, when cells were first incubated with deprenyl, a monoamine oxidase-B inhibitor for 30 min then co-incubated with rotenone plus deprenyl, a brief treatment with reserpine enhanced cell injury. CONCLUSION: Rotenone-induced apoptosis in PC12 cells was mediated by intracellular dopamine oxidation.
Hua-qing Liu; Xing-zu Zhu; En-qi Weng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta pharmacologica Sinica     Volume:  26     ISSN:  1671-4083     ISO Abbreviation:  Acta Pharmacol. Sin.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-20     Completed Date:  2005-06-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100956087     Medline TA:  Acta Pharmacol Sin     Country:  England    
Other Details:
Languages:  eng     Pagination:  17-26     Citation Subset:  IM    
Department of Pharmacology, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
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MeSH Terms
Apoptosis / drug effects*
Caspase 3
Caspases / metabolism
Dopamine / metabolism*
L-Lactate Dehydrogenase / metabolism
Lactic Acid / metabolism
Monoamine Oxidase Inhibitors / pharmacology
PC12 Cells
Reactive Oxygen Species / metabolism
Reserpine / pharmacology
Rotenone / toxicity*
Selegiline / pharmacology*
Reg. No./Substance:
0/Monoamine Oxidase Inhibitors; 0/Reactive Oxygen Species; 14611-51-9/Selegiline; 50-21-5/Lactic Acid; 50-55-5/Reserpine; 83-79-4/Rotenone; EC Dehydrogenase; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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