| Regulation of nitrite transport in red blood cells by hemoglobin oxygen fractional saturation. | |
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MedLine Citation:
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PMID: 19286940 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Allosteric regulation of nitrite reduction by deoxyhemoglobin has been proposed to mediate nitric oxide (NO) formation during hypoxia. Nitrite is predominantly an anion at physiological pH, raising questions about the mechanism by which it enters the red blood cell (RBC) and whether this is regulated and coupled to deoxyhemoglobin-mediated reduction. We tested the hypothesis that nitrite transport by RBCs is regulated by fractional saturation. Using human RBCs, nitrite consumption was faster at lower fractional saturations, consistent with faster reactions with deoxyheme. A membrane-based regulation was suggested by slower nitrite consumption with intact versus lysed RBCs. Interestingly, upon nitrite addition, intracellular nitrite concentrations attained a steady state that, despite increased rates of consumption, did not change with decreasing oxygen tensions, suggesting a deoxygenation-sensitive step that either increases nitrite import or decreases the rate of nitrite export. A role for anion exchanger (AE)-1 in the control of nitrite export was suggested by increased intracellular nitrite concentrations in RBCs treated with DIDS. Moreover, deoxygenation decreased steady-state levels of intracellular nitrite in AE-1-inhibited RBCs. Based on these data, we propose a model in which deoxyhemoglobin binding to AE-1 inhibits nitrite export under low oxygen tensions allowing for the coupling between deoxygenation and nitrite reduction to NO along the arterial-to-venous gradient. |
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Authors:
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Dario A Vitturi; Xinjun Teng; José C Toledo; Sadis Matalon; Jack R Lancaster; Rakesh P Patel |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-03-13 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 296 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-04 Completed Date: 2009-06-19 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1398-407 Citation Subset: IM |
Affiliation:
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Dept. of Pathology, Univ. of Alabama at Birmingham, 901 19th St. S., BMR-2, Rm. 302, Birmingham, AL 35294, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
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pharmacology Anion Exchange Protein 1, Erythrocyte / antagonists & inhibitors, metabolism* Anoxia / blood* Binding Sites Biological Transport Erythrocytes / drug effects, metabolism* Hemoglobins / metabolism* Humans Kinetics Methemoglobin / metabolism Models, Cardiovascular Nitric Oxide / blood Nitrites / blood* Oxidation-Reduction Oxygen / blood* Oxyhemoglobins / metabolism* Vasodilation |
| Grant Support | |
ID/Acronym/Agency:
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HL-074391/HL/NHLBI NIH HHS; HL-71189/HL/NHLBI NIH HHS; R01-HL-075540/HL/NHLBI NIH HHS; U01-ES-015676/ES/NIEHS NIH HHS; U54-ES-017218/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anion Exchange Protein 1, Erythrocyte; 0/Hemoglobins; 0/Nitrites; 0/Oxyhemoglobins; 10102-43-9/Nitric Oxide; 53005-05-3/4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; 7782-44-7/Oxygen; 9008-02-0/deoxyhemoglobin; 9008-37-1/Methemoglobin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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