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

Dario Ghigo, Maria F. Brizzi, G. Carlo Avanzi, Federico Bussolino, Giovanni Garbarino, Costanzo Costamagna, Luigi Pegoraro, Amalia Bosia

Research output: Contribution to journalArticle

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 granulocytemacrophage-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.

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalJournal of Cellular Physiology
Volume145
Issue number1
Publication statusPublished - Oct 1990

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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