| Intracellular dopamine oxidation mediates rotenone-induced apoptosis in PC12 cells. | |
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MedLine Citation:
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PMID: 15659109 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hua-qing Liu; Xing-zu Zhu; En-qi Weng |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Acta pharmacologica Sinica Volume: 26 ISSN: 1671-4083 ISO Abbreviation: Acta Pharmacol. Sin. Publication Date: 2005 Jan |
Date Detail:
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Created Date: 2005-01-20 Completed Date: 2005-06-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100956087 Medline TA: Acta Pharmacol Sin Country: England |
Other Details:
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Languages: eng Pagination: 17-26 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Caspase 3 Caspases / metabolism Dopamine / metabolism* L-Lactate Dehydrogenase / metabolism Lactic Acid / metabolism Monoamine Oxidase Inhibitors / pharmacology Oxidation-Reduction PC12 Cells Rats Reactive Oxygen Species / metabolism Reserpine / pharmacology Rotenone / toxicity* Selegiline / pharmacology* |
| Chemical | |
Reg. No./Substance:
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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 1.1.1.27/L-Lactate Dehydrogenase; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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