[Isobutyramide activates transcription of human fetal gamma-globin gene selectively].
OBJECTIVE
To examine the effect of isobutyramide synthesized in our laboratory on expression of globin genes in MEL cells transfected with the recombinant construct mu LCRA gamma psi beta delta beta MEL.


METHODS
The transformant cells were cultured in the medium containing different concentrations of isobutyramide for four days. The human gamma-, beta- and mouse alpha-globin mRNA were determined by RNase protection analysis.


RESULTS
The inducible and dose-dependent expression of the human gamma-, beta- and mouse alpha- globin gene were observed. The induction of the human gamma-globin gene was significant stronger than that of the beta-globin gene. Under 2.5 mmol/L-5 mmol/L of isobutyramide, the induction of the human gamma-globin gene was even more effective than that of mouse alpha-globin gene.


CONCLUSIONS
Isobutyramide can effectively and selectively activate transcription of the human gamma-globin gene at a certain degree. This function, together with the advantages of nontoxic and long halflife makes isobutyramide a promising application in the treatment of beta-thalassemia and sickle cell anemia.
Zhang
X
X
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC, Beijing 100005, China.
Chen
P
P
Huang
X
X
Zhang
J
J
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000577:Amides; C030197:isobutyramide; D005914:Globins