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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
Author(s) -
Ghigo Dario,
Brizzi Maria F.,
Avanzi G. Carlo,
Bussolino Federico,
Garbarino Giovanni,
Costamagna Costanzo,
Pegoraro Luigi,
Bosia Amalia
Publication year - 1990
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041450120
Subject(s) - ornithine decarboxylase , sodium–hydrogen antiporter , biology , cell culture , cell growth , medicine , endocrinology , microbiology and biotechnology , biochemistry , chemistry , enzyme , sodium , genetics , organic chemistry
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 ethylispropyl‐amiloride, 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.