Negative regulation of γ-globin gene expression by cyclic AMP-dependent pathway in erythroid cells

Akio Inoue, Yuichi Kuroyanagi, Kiminori Terui, Paolo Moi, Tohru Ikuta

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objective. Fetal hemoglobin inducers such as hemin, butyrate, and hydroxyurea stimulate γ-globin gene expression by activating the cyclic GMP (cGMP)-dependent pathway. Although cGMP activates the cyclic AMP (cAMP)-dependent pathway by suppressing cGMP-inhibited phosphodiesterase 3 (PDE3), the effects of the cAMP-dependent pathway on γ-globin gene expression are unknown. Materials and Methods. The cAMP-dependent pathway was activated in K562 cells using the adenylate cyclase activator forskolin. Expression of γ-globin mRNA was examined by primer extension, and transcriptional activity of the γ-globin gene promoter was determined by reporter gene assays. Results. PDE3 was expressed in K562 cells at a high level. The cAMP-dependent pathway was found to be activated in K562 cells in which the cGMP-dependent pathway was activated by hemin. Activation of the cAMP-dependent pathway by forskolin inhibited hemin-induced expression of γ-globin mRNA and decreased transcriptional activity of the γ-globin gene promoter. The levels of phosphorylation of mitogen-activated protein kinases (MAPKs) were not affected by the cAMP-dependent pathway. Conclusions. These results suggested that the cAMP-dependent pathway, which is independent of MAPK pathways, plays a negative role in γ-globin gene expression in K562 cells. cAMP and cGMP may have differential roles in the regulation of γ-globin gene expression in erythroid cells.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalExperimental Hematology
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Erythroid Cells
Globins
Gene Expression Regulation
Cyclic AMP
Cyclic GMP
K562 Cells
Hemin
Phosphoric Diester Hydrolases
Colforsin
Mitogen-Activated Protein Kinases
Gene Expression
Fetal Hemoglobin
Messenger RNA
Hydroxyurea
Butyrates
Reporter Genes
Adenylyl Cyclases
Genes
Phosphorylation

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Negative regulation of γ-globin gene expression by cyclic AMP-dependent pathway in erythroid cells. / Inoue, Akio; Kuroyanagi, Yuichi; Terui, Kiminori; Moi, Paolo; Ikuta, Tohru.

In: Experimental Hematology, Vol. 32, No. 3, 01.03.2004, p. 244-253.

Research output: Contribution to journalArticle

Inoue, Akio ; Kuroyanagi, Yuichi ; Terui, Kiminori ; Moi, Paolo ; Ikuta, Tohru. / Negative regulation of γ-globin gene expression by cyclic AMP-dependent pathway in erythroid cells. In: Experimental Hematology. 2004 ; Vol. 32, No. 3. pp. 244-253.
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