Butryic acid analogues augment gamma globin gene expression in neonatal erythroid progenitors.
The gamma----beta globin gene switch in humans is normally on a set developmental clock but is delayed in infants of diabetic mothers. We cultured cord blood erythroid progenitors and assayed globin produced in the presence and absence of metabolites that are elevated in such infants. Analogues of butyric acid at supranormal concentrations significantly augmented gamma and inhibited beta globin expression. The uptake of alpha-amino-n-butyric acid into colony-derived erythroblasts was increased in the presence of supranormal insulin. These findings suggest that elevated levels of alpha-amino-n-butyric acid and insulin in the developing fetus delay the globin switch and may offer potential for augmenting gamma globin expression in the beta globin chain diseases.
Children's Hospital Oakland Research Institute, California.
S P
SP
Perrine
B A
BA
Miller
M F
MF
Greene
R A
RA
Cohen
N
N
Cook
C
C
Shackleton
D V
DV
Faller
D002087:Butyrates / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005796:Genes / Q000187:drug effects*; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D011247:Pregnancy; D014158:Transcription, Genetic / Q000187:drug effects*
D002087:Butyrates; D006454:Hemoglobins; D005914:Globins