Depletion of glutamine enhances sodium butyrate-induced erythroid differentiation of K562 cells

Nguyen Canh Hiep, Seiko Kinohira, Kazumichi Furuyama, Shigeru Taketani

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Human erytholeukemia K562 cells are induced to differentiate along the erythroid lineage by a variety of chemical compounds, including hemin, sodium butyrate and 1-β-d-arabinofuranosylcytosine. We have investigated the induction of erythroid differentiation of K562 cells by glutamine depletion. When K562 cells were cultured in glutamine-minus medium, the induction of hemoglobin synthesis, accompanied by those of heme-biosynthetic enzymes and erythroid transcriptional factors, was observed. This induction was dependent on the temporally marked decrease of intracellular level of glutathione, followed by the marked activation of p38MAPK and SAPK/JNK, but not ERK. Under glutamine-deficient conditions, the treatment of K562 cells with sodium butyrate resulted in the marked enhancement of the induction of heme biosynthesis. Glutamine depletion also accelerated the expressions of erythroid-related factors including α-globin and heme-biosynthetic enzymes, GATA-1 and NF-E2, in sodium butyrate-induced K562 cells. The transcriptional activity of β-globin gene promoter-reporter was markedly enhanced by these treatments, indicating that glutamine deficiency in combination with sodium butyrate treatment gives high efficiency of chemical-induced differentiation in the hematopoiesis process.

Original languageEnglish
Pages (from-to)509-519
Number of pages11
JournalJournal of biochemistry
Issue number6
Publication statusPublished - 2012 Dec


  • Heme
  • K562 cells
  • erythroid differentiation
  • glutamine depletion
  • sodium butyrate

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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