Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 510, Issue 1, Pages 53-61Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.03.013
Keywords
Sickle cell disease; Nitric oxide; Oxygen affinity; Anti-sickling; Polymer formation
Categories
Funding
- Southeastern Clinical and Translational Research Institute
- National Institutes of Health [P20 MD003383]
- Department of Defense/Office of Naval Research
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We previously demonstrated that inhaling nitric oxide (NO) increases the oxygen affinity of sickle red blood cells (RBCs) in patients with sickle cell disease (SCD). Our recent studies found that NO lowered the P-50 values of sickle hemoglobin (HbS) hemolysates but did not increase methemoglobin (metHb) levels, supporting the role of NO, but not metHb, in the oxygen affinity of HbS. Here we examine the mechanism by which NO increases HbS oxygen affinity. Because anti-sickling agents increase sickle RBC oxygen affinity, we first determined whether NO exhibits anti-sickling properties. The viscosity of HbS hemolysates, measured by falling ball assays, increased upon deoxygenation: NO treatment reduced the increment. Multiphoton microscopic analyses showed smaller HbS polymers in deoxygenated sickle RBCs and HbS hemolysates exposed to NO. These results suggest that NO inhibits HbS polymer formation and has anti-sickling properties. Furthermore, we found that HbS treated with NO exhibits an isoelectric point similar to that of HbA, suggesting that NO alters the electric charge of HbS. NO HbS adducts had the same elution time as HbA upon high performance liquid chromatography analysis. This study demonstrates that NO may disrupt HbS polymers by abolishing the excess positive charge of HbS, resulting in increased oxygen affinity. (C) 2011 Elsevier Inc. All rights reserved.
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