Time-course of butyric acid-induced differentiation in human K562 leukemic cell line: rapid increase in g-globin, porphobilinogen deaminase and NF-E2 mRNA levels

Abstract

International audienceButyric acid (BA) was shown to induce hemoglobinization of dence of globin gene expression on the NF-E2 transcription K562 cells in a dose-and time-dependent manner. The maximal factor has been demonstrated in murine erythroleukemia differentiation (54% of hemoglobinized cells) was obtained with cells. 15 The GATA-1 transcription factor has been shown to the 0.5 mM concentration, which induced a 60% inhibition of play a central role in the control of several erythroid genes cell growth at day 3 without cytotoxicity. Parallel to the kinetics including g-globin, PBGD, erythropoietin receptor (EPOR) of hemoglobinization, a rapid increase in g-globin and porpho-bilinogen deaminase (PBGD) mRNAs was observed in BA-and GATA-1 itself. 16 treated cells. This increase was time-dependent and higher for In view of the above, we propose in this report to study the g-globin than for PBGD (six-and twofold at day 3, time-course of BA-induced hemoglobinization and erythroid respectively). In contrast, erythropoietin receptor mRNAs were mRNA overexpression in human K562 cells. By so doing, we not affected by BA treatment. Analysis of erythroid transcrip-intend to bring new insights into the involvement of GATA-1 tion factor mRNA levels during the time course of BA treatment and, especially, NF-E2 transcription factors in the BA-triggered showed, for the first time, an early and marked (up to threefold) increase in p45 NF-E2 mRNA, contrasting with that of GATA-1 differentiation process. mRNA (,1.5-fold). Taken together, these results showed the rapid differentiating effect of BA and suggest the involvement of the NF-E2 transcription factor. Materials and method