Entrapment of purified alpha-hemoglobin chains in normal erythrocytes as a model for human beta thalassemia.
Entrapment of purified alpha-hemoglobin chains within normal erythrocytes resulted in structural and functional changes very similar to those observed in human beta thalassemic erythrocytes (Table 1). Membrane proteins and reactive thiol groups were decreased in a pattern similar to that observed in vivo in beta thalassemia. In addition, the alpha-chain loaded cells exhibited evidence of enhanced oxidant stress. Functionally, entrapment of alpha-chains resulted in the loss of cellular and membrane deformability, an important pathologic characteristic of the beta thalassemic erythrocytes. These results also demonstrate that the loss of membrane proteins and thiols as well as the functional loss of cellular and membrane deformability characteristic of the beta thalassemic cell occur very rapidly in the presence of soluble alpha-chains. Utilizing this model of the thalassemic erythrocyte, it is now possible to directly investigate the mechanisms underlying the cellular pathophysiology induced by excess alpha-chains. An understanding of these mechanisms may allow for the development of therapeutic interventions that would improve effective erythropoiesis and prolong erythrocyte survival in the peripheral circulation of individuals with beta thalassemia. Successful therapeutic interventions would diminish the frequency and/or necessity of blood transfusions and chelation therapy in beta thalassemia.
Scott
M D
MD
Children's Hospital Oakland, Research Institute, CA.
D004907:Erythrocyte Deformability / Q000502:physiology; D004910:Erythrocyte Membrane; D005914:Globins / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D008954:Models, Biological; D009997:Osmotic Pressure; D010084:Oxidation-Reduction; D012016:Reference Values; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000097:blood; D017086:beta-Thalassemia / Q000097:blood*
D008565:Membrane Proteins; D013438:Sulfhydryl Compounds; D005914:Globins