Document Detail


Characterization of the mechanism and magnitude of cytoglobin-mediated nitrite reduction and nitric oxide generation under anaerobic conditions.
MedLine Citation:
PMID:  22896706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Haitao Li; Craig Hemann; Tamer M Abdelghany; Mohamed A El-Mahdy; Jay L Zweier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-15
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2012-12-28     Revised Date:  2013-10-22    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36623-33     Citation Subset:  IM    
Affiliation:
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.
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MeSH Terms
Descriptor/Qualifier:
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:
HL38324/HL/NHLBI NIH HHS; HL63744/HL/NHLBI NIH HHS; HL65608/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Nitrites; 0/cytoglobin; 10102-43-9/Nitric Oxide; 7782-44-7/Oxygen; 9004-22-2/Globins; EC 4.6.1.2/Guanylate Cyclase
Comments/Corrections

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