Na+/H+ exchange involvement in colony-stimulating factor-1-stimulated macrophage proliferation. Evidence for a requirement during late G1 of the cell cycle but not for early growth factor responses.
Na+/H+ exchange activation by growth factors is proposed to be an important early signal for mitogenesis; however, little is known of its duration and requirement during later stages of the cell cycle. Macrophage-specific colony factor (CSF-1) rapidly activates murine bone marrow-derived macrophage Na+/H+ exchange, resulting in stimulation of Na+,K(+)-ATPase activity. The response to CSF-1 is maintained for at least 24 h. Inhibition of Na+/H+ exchange with 5-N,N-dimethylamiloride prevents CSF-1-stimulated DNA synthesis and cell growth. This is unlikely to be due to cytoplasmic acidosis, but more likely reflects a requirement for Na+/H+ exchange-mediated Na+ influx. DMA addition even up to 8 h after the growth factors suppresses S-phase progression. Na+/H+ exchange appears not to be involved in the induction of other early growth factor responses (c-fos and c-myc mRNA induction and general RNA and protein synthesis). We propose that growth factor-stimulated Na+/H+ exchange late in G1 of the cell cycle is required for S-phase progression but not for certain early growth factor responses.
Vairo
G
G
University of Melbourne, Department of Medicine, Parkville, Australia.
Argyriou
S
S
Bordun
A M
AM
Gonda
T J
TJ
Cragoe
E J
EJ
Hamilton
J A
JA
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D005260:Female; D016193:G1 Phase; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008094:Lithium / Q000378:metabolism / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride; D016173:Macrophage Colony-Stimulating Factor; D008094:Lithium; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium