Abstract
S-Nitrosated hemoglobin is remarkably stable and can be cycled between deoxy, oxygenated, or oxidized forms without significant loss of NO. Here we show that S-nitrosation of adult human hemoglobin (Hb A(0)) or sickle cell Hb (Hb S) results in an increased ease of anaerobic heme oxidation, while anions cause redox shifts in the opposite direction. The negatively charged groups of the cytoplasmic domain of Band 3 protein also produce an allosteric effect on S-nitrosated Hb. Formation and deoxygenation of a SNO-Hb/Band 3 protein assembly does not in itself cause NO release, even in the presence of glutathione; however, this assembly may play a role in the migration of NO from the red blood cells to other targets and may be linked to Heinz body formation. Studies of the anaerobic oxidation of Hb S revealed an altered redox potential relative to Hb A(0) that favors met-Hb formation and may therefore underlie the increased rate of autoxidation of Hb S under aerobic conditions, the increased formation of Heinz bodies in sickle cells, and the decreased lifetime of red cells containing Hb S. A model for the interrelationships between the deoxy, oxy, and met forms of Hb A(0) and Hb S, and their S-nitrosated counterparts, is presented.
Highlights
S-Nitrosated hemoglobin is remarkably stable and can be cycled between deoxy, oxygenated, or oxidized forms without significant loss of Nitric oxide (NO)
To follow up on this parallel data analysis between oxygen binding and anaerobic oxidation, we used spectroelectrochemical methods to compare the redox behavior of Hb A0 and Hb S under varied conditions that are comparable with our oxygen binding studies
Another chapter in the study of the human health significance of Hb is beginning, in which the focus is on NO uptake and delivery by Hb A0 and the role this plays in the control of blood pressure and in oxidative and nitrosative reactions
Summary
Hb-NO, NO bound to heme of Hb; Hb equilibirum in solution and in red blood cells [5,6,7,8,9]. The shift of SNO-Hb forms of Hb A0 and Hb S toward the R-state, with higher oxygen affinity and greater ease of oxidation, probably involves a regional conformational alteration of the deoxy-Hb tetramer that prevents His146 from making its normal contribution to T-state stability. This was previously shown to be the case in Hb in which the SH-groups at Cys were modified by N-ethylmaleimide [16, 23]. Additional information regarding Band 31⁄7SNO-Hb complex formation complements that of Stamler and co-workers [19] with respect to the mechanism for NO release from SNO-Hb in vivo
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