On the induction of fetal hemoglobin by butyrates: in vivo and in vitro studies with sodium butyrate and comparison of combination treatments with 5-AzaC and AraC.
To obtain information on the cellular mechanism of induction of fetal hemoglobin (HbF) by sodium butyrate (NaB), we treated adult baboons with NaB and assessed its effects on HbF expression. Infusion of NaB increased F reticulocytes and F-positive CFUe and e-cluster colonies without induction of reticulocytosis or increase in progenitor cell numbers. Addition of NaB in bone marrow cultures increased the frequency of F-positive CFUe and e-clusters without increasing progenitor cell numbers. NaB induced HbF in human adult BFUe cultures and increased the gamma/gamma + beta globin chain and mRNA ratios in short-term incubations of culture-derived erythroblasts. There was a synergistic induction of HbF by NaB and 5-azacytidine (5-azaC), but not when the animal was treated with NaB and cytarabine (AraC). Our results suggest that the activation of gamma-globin expression by NaB reflects an action of this compound on globin genes or globin chromatin.
Constantoulakis
P
P
Department of Medicine, University of Washington, Seattle 98195.
Knitter
G
G
Stamatoyannopoulos
G
G
D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology*; D004357:Drug Synergism; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D005319:Fetal Hemoglobin / Q000096:biosynthesis*; D005914:Globins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010215:Papio
D000613:Aminobutyrates; D002087:Butyrates; D003561:Cytarabine; D005914:Globins; D005319:Fetal Hemoglobin; D001374:Azacitidine