ArticleNature medicine2008
SNO-hemoglobin is not essential for red blood cell-dependent hypoxic vasodilation.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 157 citations in OpenAlex.
- Genetic architecture of the murine red blood cell proteome reveals central role of hemoglobin beta cysteine 93 in maintaining redox balance.Cell genomics · 2026Article
- NO- and S-nitrosothiols-dependent relaxation in large and small resistance blood vessels.Frontiers in physiology · 2026Review
- How Nitric Oxide Hindered the Search for Hemoglobin-Based Oxygen Carriers as Human Blood Substitutes.International journal of molecular sciences · 2023Review
- Hemoglobin and cerebral hypoxic vasodilation in humans: Evidence for nitric oxide-dependent andJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Structural optimization and prospect of constructing hemoglobin oxygen carriers based on hemoglobin.Heliyon · 2023Review
- Control of tissue oxygenation by S-nitrosohemoglobin in human subjects.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Flipping Off and On the Redox Switch in the Microcirculation.Annual review of physiology · 2023Review
- NO and Heme Proteins: Cross-Talk between Heme and Cysteine Residues.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Article
- Red blood cell eNOS is cardioprotective in acute myocardial infarction.Redox biology · 2022Article
- A physiologically relevant role for NO stored in vascular smooth muscle cells: A novel theory of vascular NO signaling.Redox biology · 2022Review
- Optimized S-nitrosohemoglobin Synthesis in Red Blood Cells to Preserve Hypoxic Vasodilation ViaThe Journal of pharmacology and experimental therapeutics · 2022Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Hypoxic vasodilatory defect and pulmonary hypertension in mice lacking hemoglobin β-cysteine93 S-nitrosylation.JCI insight · 2022Article
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
- Red Blood Cell-Mediated S-Nitrosohemoglobin-Dependent Vasodilation: Lessons Learned from a β-Globin Cys93 Knock-In Mouse.Antioxidants & redox signaling · 2021Review
- Essential Role of Hemoglobin βCys93 in Cardiovascular Physiology.Physiology (Bethesda, Md.) · 2020Review
- Role of Nitric Oxide Carried by Hemoglobin in Cardiovascular Physiology: Developments on a Three-Gas Respiratory Cycle.Circulation research · 2020Review
- Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.Blood advances · 2019Article
19 more citing papers are in PubMed but not listed here.
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16 authors at 2 institutions in 1 country.
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Abstract
The coupling of hemoglobin sensing of physiological oxygen gradients to stimulation of nitric oxide (NO) bioactivity is an established principle of hypoxic blood flow. One mechanism proposed to explain this oxygen-sensing-NO bioactivity linkage postulates an essential role for the conserved Cys93 residue of the hemoglobin beta-chain (betaCys93) and, specifically, for S-nitrosation of betaCys93 to form S-nitrosohemoglobin (SNO-Hb). The SNO-Hb hypothesis, which conceptually links hemoglobin and NO biology, has been debated intensely in recent years. This debate has precluded a consensus on physiological mechanisms and on assessment of the potential role of SNO-Hb in pathology. Here we describe new mouse models that exclusively express either human wild-type hemoglobin or human hemoglobin in which the betaCys93 residue is replaced with alanine to assess the role of SNO-Hb in red blood cell-mediated hypoxic vasodilation. Substitution of this residue, precluding hemoglobin S-nitrosation, did not change total red blood cell S-nitrosothiol abundance but did shift S-nitrosothiol distribution to lower molecular weight species, consistent with the loss of SNO-Hb. Loss of betaCys93 resulted in no deficits in systemic or pulmonary hemodynamics under basal conditions and, notably, did not affect isolated red blood cell-dependent hypoxic vasodilation. These results demonstrate that SNO-Hb is not essential for the physiologic coupling of erythrocyte deoxygenation with increased NO bioactivity in vivo.
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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.