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Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell.
- Source :
-
Circulation [Circulation] 2019 Jun 04; Vol. 139 (23), pp. 2654-2663. Date of Electronic Publication: 2019 Mar 25. - Publication Year :
- 2019
-
Abstract
- Background: Nitrosation 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.<br />Methods: To 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.<br />Results: In 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.<br />Conclusions: RBCs clearly have the fascinating ability to export NO bioactivity, but this occurs independently of SNO formation at the β93 cysteine of Hb.
- Subjects :
- Alanine
Amino Acid Substitution
Animals
Biological Transport
Cysteine
Disease Models, Animal
Hemoglobins genetics
Humans
Hypoxia blood
Hypoxia physiopathology
Isolated Heart Preparation
Male
Mice, Inbred C57BL
Mice, Transgenic
Mutation
Myocardial Reperfusion Injury physiopathology
Platelet Activation
Rats, Sprague-Dawley
Vasodilation
Ventricular Function, Left
Ventricular Pressure
beta-Globins genetics
Blood Platelets metabolism
Erythrocytes metabolism
Hemoglobins metabolism
Myocardial Reperfusion Injury blood
Nitric Oxide blood
Skin blood supply
beta-Globins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 139
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 30905171
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.118.039284