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alpha-Amino-N-butyric acid stimulates fetal hemoglobin in the adult
P Constantoulakis, T Papayannopoulou and G Stamatoyannopoulos
Department of Medicine, University of Washington, Seattle.
The effect of alpha-amino-N-butyric acid (alpha ABA) on fetal hemoglobin
production in the adult was examined in vivo after being administered to
normal and anemic baboons and in erythroid progenitor cell cultures.
Infusion of alpha ABA for five days resulted in four- to fivefold increases
in the level of F reticulocytes of normal or chronically anemic baboons.
The induction of HbF by alpha ABA was strikingly enhanced by the
administration of 5-azacytidine. The addition of alpha ABA in culture
produced a concentration-related increase of HbF in baboon CFUe and
e-cluster colonies. In addition to the induction of HbF, alpha ABA
stimulated the growth of all classes of erythroid progenitors in vivo or in
culture. The activation of gamma- globin gene expression by alpha ABA is
attributed to an interaction between regulatory sites of globin chromatin
modified by alpha ABA and the immature intracellular environment of the
expanding erythropoiesis. The combination of chromatin modification, DNA
methylation, and the immature intracellular environment of rapid erythroid
regeneration may explain the synergistic induction of HbF by alpha ABA and
5-azacytidine.
Volume 72,
Issue 6,
pp. 1961-1967,
12/01/1988
Copyright © 1988 by The American Society of Hematology
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