Induction of fetal hemoglobin synthesis by valproate: modulation of MAP kinase pathways

Am J Hematol. 2002 Sep;71(1):45-6. doi: 10.1002/ajh.10161.

Abstract

Valproate has been found to stimulate fetal hemoglobin (HbF) synthesis in patients with sickle cell disease. In accordance with these clinical observations, we found a moderate induction of HbF synthesis in K562 erythroid cells in vitro. Investigation of the role of the mitogen-activated protein kinase (MAPK) pathways by Western blot analysis and use of specific kinase inhibitors suggests that inhibition of ERK pathway and activation of the p38 pathway may contribute to the HbF-inducing activity of valproate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Butadienes / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fetal Hemoglobin / biosynthesis*
  • Fetal Hemoglobin / genetics
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Imidazoles / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • K562 Cells / drug effects
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / genetics
  • Mitogen-Activated Protein Kinase 1 / biosynthesis
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / biosynthesis
  • Mitogen-Activated Protein Kinases / genetics
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Nitriles / pharmacology
  • Phosphorylation
  • Protein Processing, Post-Translational / drug effects
  • Pyridines / pharmacology
  • Valproic Acid / pharmacology*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Imidazoles
  • Neoplasm Proteins
  • Nitriles
  • Pyridines
  • U 0126
  • Valproic Acid
  • Fetal Hemoglobin
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580