| H(2)O(2)-induced O(2) production by a non-phagocytic NAD(P)H oxidase causes oxidant injury. | |
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MedLine Citation:
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PMID: 11358965 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Non-phagocytic NAD(P)H oxidases have been implicated as major sources of reactive oxygen species in blood vessels. These oxidases can be activated by cytokines, thereby generating O(2), which is subsequently converted to H(2)O(2) and other oxidant species. The oxidants, in turn, act as important second messengers in cell signaling cascades. We hypothesized that reactive oxygen species, themselves, can activate the non-phagocytic NAD(P)H oxidases in vascular cells to induce oxidant production and, consequently, cellular injury. The current report demonstrates that exogenous exposure of non-phagocytic cell types of vascular origin (smooth muscle cells and fibroblasts) to H(2)O(2) activates these cell types to produce O(2) via an NAD(P)H oxidase. The ensuing endogenous production of O(2) contributes significantly to vascular cell injury following exposure to H(2)O(2). These results suggest the existence of a feed-forward mechanism, whereby reactive oxygen species such as H(2)O(2) can activate NAD(P)H oxidases in non-phagocytic cells to produce additional oxidant species, thereby amplifying the vascular injury process. Moreover, these findings implicate the non-phagocytic NAD(P)H oxidase as a novel therapeutic target for the amelioration of the biological effects of chronic oxidant stress. |
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Authors:
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W G Li; F J Miller; H J Zhang; D R Spitz; L W Oberley; N L Weintraub |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2001-05-17 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 276 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2001 Aug |
Date Detail:
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Created Date: 2001-07-30 Completed Date: 2001-09-13 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 29251-6 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Survival / drug effects* Cells, Cultured Coronary Vessels / cytology, enzymology, physiology* Fibroblasts / cytology, physiology Humans Hydrogen Peroxide / pharmacology* Male Membrane Glycoproteins / deficiency, genetics, metabolism Mice Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular / cytology, enzymology, physiology* NADH, NADPH Oxidoreductases / metabolism* NADPH Oxidase / metabolism Oxidants / pharmacology* Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Recombinant Proteins / metabolism Rotenone / pharmacology Superoxides / metabolism* Transfection |
| Grant Support | |
ID/Acronym/Agency:
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CA66081/CA/NCI NIH HHS; HL49264/HL/NHLBI NIH HHS; HL62984/HL/NHLBI NIH HHS; K08 HL003669-03/HL/NHLBI NIH HHS; K08 HL003669-04/HL/NHLBI NIH HHS; K08 HL003669-05/HL/NHLBI NIH HHS; R01 HL51469/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CYBB protein, human; 0/Membrane Glycoproteins; 0/Oxidants; 0/Reactive Oxygen Species; 0/Recombinant Proteins; 11062-77-4/Superoxides; 7722-84-1/Hydrogen Peroxide; 83-79-4/Rotenone; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.1/NADPH Oxidase |
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