| The highly expressed and inducible endogenous NAD(P)H:quinone oxidoreductase 1 in cardiovascular cells acts as a potential superoxide scavenger. | |
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MedLine Citation:
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PMID: 17901563 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has recently been demonstrated that purified NAD(P)H:quinone oxidoreductase 1 (NQO1) is able to scavenge superoxide (O2(.-)) though the rate of reaction of O2(.-) with NQO1 is much lower than the rate of enzymatic dismutation catalyzed by superoxide dismutase (SOD). This study was undertaken to determine if the endogenously expressed NQO1 in cardiovascular cells could scavenge O2(.-). We observed that NQO1 was highly expressed in cardiovascular cells, including rat aortic smooth muscle A10 and cardiac H9c2 cells, as well as normal human aortic smooth muscle and endothelial cells. NQO1, but not SOD in the cardiovascular cells was highly inducible by 3H-1,2-dithiole-3-thione (D3T). Cytosols from H9c2 and human aortic smooth muscle cells (HASMCs) were isolated to determine the O2(.-) scavenging ability of the endogenously expressed NQO1 by using pyrogallol autooxidation assay. We showed that cytosols from the above cells inhibited pyrogallol autooxidation in an NADPH or NADH-dependent manner. The NADH/NADPH-dependent inhibition of pyrogallol autooxidation by the cytosols was completely abolished by the NQO1-specific inhibitor, ES936, suggesting that the endogenously expressed NQO1 could scavenge O2(.-). In the presence of NADH/NADPH, cytosols from D3T-treated cells showed increased ability to scavenge O2(.-) as compared to cytosols from untreated cells. This increased ability to scavenge O2(.-) was also completely reversed by ES936. 5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide spin-trapping experiments using potassium superoxide as a O2(.-) generator further confirmed the ability of NQO1 from HASMCs to scavenge O2(.-). The spin-trapping experiments also showed that induction of NQO1 by D3T in HASMCs augmented the O2(.-) scavenging ability. Taken together, these results demonstrate that the highly expressed and inducible endogenous NQO1 in cardiovascular cells may act as a potential O2(.-) scavenger. |
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Authors:
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Hong Zhu; Zhenquan Jia; James E Mahaney; David Ross; Hara P Misra; Michael A Trush; Yunbo Li |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cardiovascular toxicology Volume: 7 ISSN: 1530-7905 ISO Abbreviation: Cardiovasc. Toxicol. Publication Date: 2007 |
Date Detail:
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Created Date: 2007-09-28 Completed Date: 2007-11-27 Revised Date: 2012-05-28 |
Medline Journal Info:
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Nlm Unique ID: 101135818 Medline TA: Cardiovasc Toxicol Country: United States |
Other Details:
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Languages: eng Pagination: 202-11 Citation Subset: IM |
Affiliation:
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Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Research Building II, 1861 Pratt Drive, Blacksburg, VA 24060, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / metabolism Cardiovascular System / cytology, drug effects, enzymology* Cell Line Cytosol / metabolism Electron Spin Resonance Spectroscopy Endothelium, Vascular / cytology, drug effects, enzymology Enzyme Induction Free Radical Scavengers / metabolism* Gene Expression Regulation, Enzymologic Humans Indolequinones / pharmacology Muscle, Smooth, Vascular / cytology, drug effects, enzymology Myocytes, Cardiac / cytology, drug effects, enzymology NAD(P)H Dehydrogenase (Quinone) / biosynthesis*, genetics Oxidation-Reduction Pyrogallol / metabolism, pharmacology RNA, Messenger / metabolism Rats Superoxides / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL71190/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/5-methoxy-1,2-dimethyl-3-((4-nitrophenoxy)methyl)indole-4,7-dione; 0/Antioxidants; 0/Free Radical Scavengers; 0/Indolequinones; 0/RNA, Messenger; 11062-77-4/Superoxides; 87-66-1/Pyrogallol; EC 1.6.5.2/NAD(P)H Dehydrogenase (Quinone); EC 1.6.5.2/NQO1 protein, human; EC 1.6.5.2/NQO1 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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