| Characterization of the mechanism and magnitude of cytoglobin-mediated nitrite reduction and nitric oxide generation under anaerobic conditions. | |
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MedLine Citation:
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PMID: 22896706 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytoglobin (Cygb) is a recently discovered cytoplasmic heme-binding globin. Although multiple hemeproteins have been reported to function as nitrite reductases in mammalian cells, it is unknown whether Cygb can also reduce nitrite to nitric oxide (NO). The mechanism, magnitude, and quantitative importance of Cygb-mediated nitrite reduction in tissues have not been reported. To investigate this pathway and its quantitative importance, EPR spectroscopy, spectrophotometric measurements, and chemiluminescence NO analyzer studies were performed. Under anaerobic conditions, mixing nitrite with ferrous-Cygb triggered NO formation that was trapped and detected using EPR spin trapping. Spectrophotometric studies revealed that nitrite binding to ferrous-Cygb is followed by formation of ferric-Cygb and NO. The kinetics and magnitude of Cygb-mediated NO formation were characterized. It was observed that Cygb-mediated NO generation increased linearly with the increase of nitrite concentration under anaerobic conditions. This Cygb-mediated NO production greatly increased with acidosis and near-anoxia as occur in ischemic conditions. With the addition of nitrite, soluble guanylyl cyclase activation was significantly higher in normal smooth muscle cells compared with Cygb knocked down cells with Cygb accounting for ∼40% of the activation in control cells and ∼60% in cells subjected to hypoxia for 48 h. Overall, these studies show that Cygb-mediated nitrite reduction can play an important role in NO generation and soluble guanylyl cyclase activation under hypoxic conditions, with this process regulated by pH, oxygen tension, nitrite concentration, and the redox state of the cells. |
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Authors:
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Haitao Li; Craig Hemann; Tamer M Abdelghany; Mohamed A El-Mahdy; Jay L Zweier |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-08-15 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 287 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-22 Completed Date: 2012-12-28 Revised Date: 2013-04-16 |
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: 36623-33 Citation Subset: IM |
Affiliation:
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Center for Biomedical EPR Spectroscopy and Imaging, the Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, Ohio 43210, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anaerobiosis Cell Hypoxia / physiology Cells, Cultured Electron Spin Resonance Spectroscopy Globins / chemistry, genetics, metabolism* Guanylate Cyclase / chemistry, genetics, metabolism Humans Hydrogen-Ion Concentration Kinetics Luminescent Measurements Myocytes, Smooth Muscle / cytology, metabolism* Nitric Oxide / chemistry, metabolism* Nitrites / chemistry, metabolism* Oxidation-Reduction Oxygen / chemistry, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL38324/HL/NHLBI NIH HHS; HL63744/HL/NHLBI NIH HHS; HL65608/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Nitrites; 0/cytoglobin; 10102-43-9/Nitric Oxide; 7782-44-7/Oxygen; 9004-22-2/Globins; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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