Abstract
In sickle cell trait (SCT), hemoglobin A (HbA) and S (HbS) are co-expressed in each red blood cell (RBC). While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic anemia, painful vaso-occlusive episodes and shortened life-span, SCT is considered a benign condition usually with minor or no complications related to sickling. However, physical activities that cause increased tissue oxygen demand, dehydration and/or metabolic acidosis leads to increased HbS polymerization and life-threatening complications including death. We report that GBT440, an agent being developed for the treatment of SCD, increases the affinity of oxygen for Hb and inhibits in vitro polymerization of a mixture of HbS and HbA that simulates SCT blood. Moreover, GBT440 prevents sickling of SCT blood under in vitro conditions mimicking strenuous exercise with hypoxia, dehydration and acidosis. Together, our results indicate that GBT440 may have the potential to protect SCT individuals from sickling-related complications during conditions that favor HbS polymerization.
Highlights
(HbA) and S (HbS) are co-expressed in each hypothermia, increased red blood cells (RBCs) 2.3-DPG concenred blood cell (RBC)
While homozygous expression of HbS (HbSS) leads to polymerization and sickling of RBCs resulting in sickle cell disease (SCD) characterized by hemolytic ly anemia, painful vaso-occlusive episodes and n shortened life-span, sickle cell trait (SCT) is considered a benign condition usually with minor or no o complications related to sickling
In the inheritance of normal and sickle -globin addition, we demonstrate that GBT440 pre- Buffers alleles resulting in the expression of both hemoglobin A (HbA) and S (HbS) in red blood cells (RBCs)
Summary
Gel filtration and DE-52 anion exchange chromatography were used to purify HbS or HbA expressed within RBCs. As a consequence, Sodium citrate anticoagulated whole blood from sickle cell or normal donor RBC lysates, polymerization of deoxy-HbS and sickling of from sickle cell patients was obtained from respectively.[15] Samples of the eluted fractions [Hematology Reports 2016; 8:6637]. Article were run on a Tris-glycine 12% acrylamide Whole blood oxygen equilibrium function of the partial pressure of oxygen native gel where they were separated according to their isoelectric point allowing for their identification. Purified HbS or HbA was buffer exchanged into 1.8 M KH2PO4 at pH 7.4, flash frozen with liquid nitrogen and stored at -80°C
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
