ArticleThe Journal of biological chemistry2015
Mechanisms of human erythrocytic bioactivation of nitrite.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Protective role of nitric oxide donors on endothelium in ischemia-reperfusion injury: a meta-analysis of randomized controlled trials.BMC anesthesiology · 2023Pooled it
- Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome.Hypertension (Dallas, Tex. : 1979) · 2020Trial
- Conjugated Linoleic Acid Modulates Clinical Responses to Oral Nitrite and Nitrate.Hypertension (Dallas, Tex. : 1979) · 2017Trial
- Pharmacokinetics and Pharmacodynamics of Inorganic Nitrate in Heart Failure With Preserved Ejection Fraction.Circulation research · 2017Trial
- Article
- Hemoglobin as an oxygen gasoreceptor.Acta biochimica Polonica · 2025Review
- Nitrosyl hemoglobin formation from nitrite in normal and sickle blood.Free radical biology & medicine · 2024Article
- Review
- Design, Synthesis, and Antisickling Investigation of a Nitric Oxide-Releasing Prodrug of 5HMF for the Treatment of Sickle Cell Disease.Biomolecules · 2022Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Human and rodent red blood cells do not demonstrate xanthine oxidase activity or XO-catalyzed nitrite reduction to NO.Free radical biology & medicine · 2021Article
- Essential Role of Hemoglobin βCys93 in Cardiovascular Physiology.Physiology (Bethesda, Md.) · 2020Review
- Cellular microdomains for nitric oxide signaling in endothelium and red blood cells.Nitric oxide : biology and chemistry · 2020Review
- Carbonic anhydrase II does not regulate nitrite-dependent nitric oxide formation and vasodilation.British journal of pharmacology · 2020Article
- Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell.Circulation · 2019Article
- Carbonic anhydrase is not a relevant nitrite reductase or nitrous anhydrase in the lung.The Journal of physiology · 2019Article
- Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their RegulationPhysiological reviews · 2019Review
- Double-Blind Clinical Trial of Arginine Supplementation in the Treatment of Adult Patients with Sickle Cell Anaemia.Advances in hematology · 2019Article
- Erythrocytic bioactivation of nitrite and its potentiation by far-red light.Redox biology · 2019Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Nitrite signaling likely occurs through its reduction to nitric oxide (NO). Several reports support a role of erythrocytes and hemoglobin in nitrite reduction, but this remains controversial, and alternative reductive pathways have been proposed. In this work we determined whether the primary human erythrocytic nitrite reductase is hemoglobin as opposed to other erythrocytic proteins that have been suggested to be the major source of nitrite reduction. We employed several different assays to determine NO production from nitrite in erythrocytes including electron paramagnetic resonance detection of nitrosyl hemoglobin, chemiluminescent detection of NO, and inhibition of platelet activation and aggregation. Our studies show that NO is formed by red blood cells and inhibits platelet activation. Nitric oxide formation and signaling can be recapitulated with isolated deoxyhemoglobin. Importantly, there is limited NO production from erythrocytic xanthine oxidoreductase and nitric-oxide synthase. Under certain conditions we find dorzolamide (an inhibitor of carbonic anhydrase) results in diminished nitrite bioactivation, but the role of carbonic anhydrase is abrogated when physiological concentrations of CO2 are present. Importantly, carbon monoxide, which inhibits hemoglobin function as a nitrite reductase, abolishes nitrite bioactivation. Overall our data suggest that deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions and accounts for nitrite-mediated NO signaling in blood.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.