Time-course of butyric acid-induced differentiation in human K562 leukemic cell line: rapid increase in gamma-globin, porphobilinogen deaminase and NF-E2 mRNA levels.
Butyric acid (BA) was shown to induce hemoglobinization of K562 cells in a dose- and time-dependent manner. The maximal differentiation (54% of hemoglobinized cells) was obtained with the 0.5 mM concentration, which induced a 60% inhibition of cell growth at day 3 without cytotoxicity. Parallel to the kinetics of hemoglobinization, a rapid increase in gamma-globin and porphobilinogen deaminase (PBGD) mRNAs was observed in BA-treated cells. This increase was time-dependent and higher for gamma-globin than for PBGD (six- and two-fold at day 3, respectively). In contrast, erythropoietin receptor mRNAs were not affected by BA treatment. Analysis of erythroid transcription factor mRNA levels during the time course of BA treatment showed, for the first time, an early and marked (up to three-fold) increase in p45 NF-E2 mRNA, contrasting with that of GATA-1 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.
Chénais
B
B
Laboratoire de Biochimie et Biologie Moléculaire, EA2063, IFR53-Biomolécules, Faculté de Pharmacie, Université de Reims Champagne Ardenne, France.
Molle
I
I
Trentesaux
C
C
Jeannesson
P
P
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000187:drug effects; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005914:Globins / Q000235:genetics*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000096:biosynthesis*; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D012333:RNA, Messenger / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002087:Butyrates; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D014157:Transcription Factors; D020148:Butyric Acid; D005914:Globins; D011163:Hydroxymethylbilane Synthase