ArticleCirculation2019
Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
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- Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Age affects the association of red blood cell indices with efficacy of remote ischemic conditioning in patients with acute moderate ischemic stroke.Scientific reports · 2024Article
- 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
- Stimulation of Erythrocyte Soluble Guanylyl Cyclase Induces cGMP Export and Cardioprotection in Type 2 Diabetes.JACC. Basic to translational science · 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
- Endothelial alpha globin is a nitrite reductase.Nature communications · 2022Article
- Erythrocyte oxidative stress and thrombosis.Expert reviews in molecular medicine · 2022Review
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- 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
- Nitric Oxide Production and Regulation in the Teleost Cardiovascular System.Antioxidants (Basel, Switzerland) · 2022Review
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- The enzymatic function of the honorary enzyme: S-nitrosylation of hemoglobin in physiology and medicine.Molecular aspects of medicine · 2022Review
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNitrosation of a conserved cysteine residue at position 93 in the hemoglobin β chain (β93C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection.
methodsTo test this hypothesis, we used RBCs from mice in which the β93 cysteine had been replaced with alanine (β93A) in a number of ex vivo and in vivo models suitable for studying export of NO bioactivity.
resultsIn an ex vivo model of cardiac ischemia/reperfusion injury, perfusion of a mouse heart with control RBCs (β93C) pretreated with an arginase inhibitor to facilitate export of RBC NO bioactivity improved cardiac recovery after ischemia/reperfusion injury, and the response was similar with β93A RBCs. Next, when human platelets were coincubated with RBCs and then deoxygenated in the presence of nitrite, export of NO bioactivity was detected as inhibition of ADP-induced platelet activation. This effect was the same in β93C and β93A RBCs. Moreover, vascular reactivity was tested in rodent aortas in the presence of RBCs pretreated with S-nitrosocysteine or with hemolysates or purified Hb treated with authentic NO to form nitrosyl(FeII)-Hb, the proposed precursor of SNO-Hb. SNO-RBCs or NO-treated Hb induced vasorelaxation, with no differences between β93C and β93A RBCs. Finally, hypoxic microvascular vasodilation was studied in vivo with a murine dorsal skin-fold window model. Exposure to acute systemic hypoxia caused vasodilatation, and the response was similar in β93C and β93A mice.
conclusionsRBCs clearly have the fascinating ability to export NO bioactivity, but this occurs independently of SNO formation at the β93 cysteine of Hb.
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