Oxidative damage and erythrocyte membrane transport abnormalities in thalassemias.
Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have evaluated transport of Na+ and K+ in erythrocytes of patients with thalassemias as well as in two experimental models that use normal human red blood cells, one for alpha thalassemia (methylhydrazine treatment, alpha thalassemia like) and one for beta thalassemia (phenylhydrazine treatment, beta thalassemia like). With the exception of the Na-K pump, similar alterations in membrane transport were observed in thalassemia and thalassemia-like erythrocytes. These were: increased K-Cl cotransport, Na-Li countertransport and reduced Na-K-Cl cotransport. The Na-K pump was reduced in thalassemia-like cells, whereas it was increased in severe alpha thalassemia and in beta thalassemia cells. The increased K-Cl cotransport activity could be observed in light and dense fractions of beta-thalassemic cells. K-Cl cotransport in thalassemic and thalassemia-like erythrocytes was partially inhibited by [(dihydro-indenyl) oxy] alkanoic acid and completely abolished by dithiothreitol. Thus, oxidative damage represents an important factor in the increased activity of the K-Cl cotransport observed in thalassemias, and of the K+ loss observed in beta-thalassemia erythrocytes.
Olivieri
O
O
Department of Internal Medicine, University of Verona, Italy.
De Franceschi
L
L
Capellini
M D
MD
Girelli
D
D
Corrocher
R
R
Brugnara
C
C
D002712:Chlorides / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport; D009002:Monomethylhydrazine / Q000494:pharmacology; D010659:Phenylhydrazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase; D013789:Thalassemia / Q000378:metabolism*
D002712:Chlorides; D010659:Phenylhydrazines; C030299:phenylhydrazine; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009002:Monomethylhydrazine