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  • Title: [Isobutyramide activates transcription of human fetal gamma-globin gene selectively].
    Author: Zhang X, Chen P, Huang X, Zhang J.
    Journal: Zhongguo Yi Xue Ke Xue Yuan Xue Bao; 2000 Oct; 22(5):444-8. PubMed ID: 12903425.
    Abstract:
    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. CONCLUSION: 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.
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