Evidence for a role of the Na+/H+ exchanger in the colony-stimulating-factor-induced ornithine decarboxylase activity and proliferation of the human cell line M-07e

J Cell Physiol. 1990 Oct;145(1):147-54. doi: 10.1002/jcp.1041450120.

Abstract

The subclone M-07e, derived from the interleukin-3 (IL-3)-responsive human myeloid cell line M-07, is strictly dependent on either IL-3 or granulocyte-macrophage-colony-stimulating factor (GM-CSF) for its growth and survival. This cell line may be regarded as a candidate model to investigate the poorly understood events triggered by growth factors binding to human hemopoietic cells. Both IL-3 and GM-CSF induce in M-07e cells an increase of ornithine decarboxylase (ODC) activity, which reaches its maximum at 24-30 h and fully depends on de novo protein synthesis. The growth factors do not elicit translocation of protein kinase C to the membrane; thus a role of the kinase in ODC induction is ruled out. An amiloride-inhibitable Na+/H+ exchanger is present in the membrane of M-07e cells; its apparent Km for extracellular Na+ is 47.77 mM; and its activity is greatly enhanced when the cytoplasm is acidified. Growth-factor-evoked ODC activation and DNA synthesis are blocked in a dose- and time-dependent manner when M-07e cells are incubated with ethylisopropylamiloride, a specific inhibitor of Na+/H+ exchanger. The exchanger does not appear to be directly activated by IL-3 or GM-CSF, but its operation is strictly required for the biological effects of these growth factors on M-07e cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / analogs & derivatives
  • Amiloride / pharmacology
  • Carrier Proteins / physiology*
  • Cell Division / physiology
  • Cell Line
  • DNA Replication / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Interleukin-3 / physiology*
  • Ornithine Decarboxylase / metabolism*
  • Protein Kinase C / physiology*
  • Sodium-Hydrogen Exchangers
  • Subcellular Fractions / enzymology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Thymidine / metabolism
  • Tritium

Substances

  • Carrier Proteins
  • Interleukin-3
  • Sodium-Hydrogen Exchangers
  • Tritium
  • Amiloride
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Protein Kinase C
  • Ornithine Decarboxylase
  • Tetradecanoylphorbol Acetate
  • Thymidine
  • ethylisopropylamiloride