Mechanisms of sirolimus inducing expression of γ-globin gene in K562 cells / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the mechanisms of sirolimus inducing γ-globin gene expression in K562 cells. METHODS: K562 cells were cultured in the presence of 10 nmol · L-1 sirolimus, butylate, or DMSO for 3 d. Western blot and real time PCR-based chromatin immunoprecipitation was employed to measure the levels of p38MAPK and acetylated histone H3 (acH3) at γ-globin gene promoter regions, respectively. RESULTS: In K562 cells with 10 nmol · L-1 sirolimus treatment, phospholylated p38MAPK (p-p38MAPK) was 2.8-fold greater and acH3 was 9.8-fold greater than that in untreated K562 cells, and there was a 2.9-fold in p-p38MAPK and a 9.1-fold in acH3 increase comparing with K562 cells treated with DMSO, no significant difference in p-p38MAPK and acH3 level was found between cells treated with sirolimus and with butylate. SB203580 completely abolished induction of p38MAPK activation and acH3 increase by sirolimus. CONCLUSION: Our results indicate that sirolimus actives p38MAPK signal and increases acetylation of H3 at γ-globin gene promoter regions, which may be the mechanisms of induced expression of γ-globin genes by sirolimus in K562 cells.