Proteolytic activity in erythrocyte precursors

Abstract

Thalassemia is characterized by unequal rates of synthesis of .alpha. and .beta. globin chains that are part of the Hb tetramer. In the type of thalassemia due to a defect in .beta.-chain synthesis (.beta.-thalassemia), this imbalance results in a relative excess of .alpha.-chains. The susceptibility of excess free [human] .alpha.-chains to proteolysis was studied. Incubation of isotopically labeled peripheral blood lysates from individuals with .beta.-thalassemia trait in the presence of bone marrow or normoblast lysates from thalassemic or hematologically normal individuals resulted in a decrease in the .alpha./.beta. ratio and a loss of free .alpha.-chain radioactivity. Neither contamination with leukocytes nor higher ATP contents in young erythrocytes appeared to be responsible for this activity in normoblasts and bone marrow. Erythroid precursor cells may possess proteolytic activity that is markedly diminished in mature cells. This activity serves an important control function in the regulation of Hb synthesis. It accounts at least in part for the more balanced synthesis of .alpha.- and .beta.-chains observed in bone marrow than in peripheral blood in heterozygous .beta.-thalassemia. It also plays a fine-tuning role in maintaining balanced synthesis in non-thalassemic erythrocytes.