Regulation of hemoglobin beta-chain synthesis in bone marrow erythroid cells by alpha chains.

Synthesis of alpha and beta chains of hemoglobin was studied in vitro in intact reticulocytes and bone marrow cells. The cells were from rabbits having a variant form of hemoglobin in which L-isoleucine is in the alpha but not in the beta chains. This characteristic permitted a selective inhibition of alpha-chain synthesis to be produced by addition to the incubation medium of L-O-methylthreonine, an inhibitor of protein synthesis that is a specific antagonist of L-isoleucine. In studies with reticulocytes, 25 mM L-O-methylthreonine produced a 60-70% inhibition of alpha-chain synthesis, but beta-chain synthesis was unaffected even after incubation times for 4 hr. Because reticulocytes contain a pool of uncombined alpha chains which might have obscured the demonstration of an alpha chain-dependent mechanism for beta-chain synthesis, subsequent studies were done with bone marrow cells. The latter had little or no detectable alpha-chain pool. A substantial inhibition of alpha-chain synthesis by the bone marrow cells was produced by the isoleucine antagonist but was also accompanied by a significantly decreased rate of beta-chain synthesis. These findings suggest that the coordinated synthesis of the complementary alpha- and beta-globin chains of hemoglobin may reflect in part a modifying effect of alpha-chain synthesis on the synthesis of beta chains.