| Overexpression of NQO1 protects human SK-N-MC neuroblastoma cells against dopamine-induced cell death. | |
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MedLine Citation:
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PMID: 16978807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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NAD(P)H quinone oxidoreductase 1 (NQO1) can metabolize dopamine-derived quinones (DAQ) and absence of NQO1 due to the NQO1*2 polymorphism has been suggested to be a risk factor for Parkinson's disease. In order to define whether NQO1 plays a protective role in dopamine toxicity, we have examined the potential role of NQO1 in the SK-N-MC human neuroblastoma cell line. SK-N-MC cells were stably transfected with NQO1 to generate stable clones with NQO1 enzymatic activity of 245 nmol/mgmin while vector control and parental cells had NQO1 activities of less than 12 nmol/mgmin. Incubation of dopamine for 24 h in both parental and vector control SK-N-MC cells resulted in 85% and 72% cell death as assessed by annexin-V/propidium iodide analysis. In agreement, 88% and 84% of parental and vector control cells, respectively underwent loss of mitochondrial membrane potential (MMP) assessed by tetramethylrhodamine ethyl ester. In contrast, NQO1-transfected cells were resistant to dopamine toxicity and both cell death and loss of MMP were markedly abrogated in NQO1-transfected SK-N-MC cells. When dopamine was added to medium, oxygen uptake could be detected indicating autoxidation with concomitant formation of oxygen radicals and quinones. However, dopamine-induced cell death was not affected by the inclusion of either superoxide dismutase or catalase suggesting that superoxide and hydrogen peroxide were not involved in toxicity. Quinones formed in medium may exert toxicity extracellularly or intracellularly but the protective role of NQO1 argues for an intracellular mechanism. In summary, transfection of SK-N-MC cells with NQO1 protects against dopamine-induced toxicity. |
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Authors:
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K S Zafar; S H Inayat-Hussain; D Siegel; A Bao; B Shieh; D Ross |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-08-15 |
Journal Detail:
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Title: Toxicology letters Volume: 166 ISSN: 0378-4274 ISO Abbreviation: Toxicol. Lett. Publication Date: 2006 Oct |
Date Detail:
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Created Date: 2006-09-27 Completed Date: 2006-11-14 Revised Date: 2012-05-28 |
Medline Journal Info:
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Nlm Unique ID: 7709027 Medline TA: Toxicol Lett Country: Netherlands |
Other Details:
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Languages: eng Pagination: 261-7 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Annexin A5
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diagnostic use Apoptosis / drug effects Blotting, Western Brain Neoplasms / pathology* Catalase / metabolism Cell Death / drug effects Cell Line, Tumor Dopamine / toxicity* Flow Cytometry Free Radicals Humans Membrane Potentials / drug effects Mitochondrial Membranes / drug effects NAD(P)H Dehydrogenase (Quinone) / biosynthesis*, physiology Neuroblastoma / pathology* Quinones / metabolism Superoxide Dismutase / metabolism Transfection |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS44613/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Annexin A5; 0/Free Radicals; 0/Quinones; EC 1.11.1.6/Catalase; EC 1.15.1.1/Superoxide Dismutase; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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