The Na+/H+ antiporter potentiates growth and retinoic acid-induced differentiation of P19 embryonal carcinoma cells.
The Na+/H+ exchanger is a ubiquitous plasma membrane protein that is responsible for pH regulation and is activated by growth factors. We examined the role of the Na+/H+ exchanger in cell growth and differentiation. Treatment of P19 cells with the Na+/H+ exchanger inhibitor Hoe 694 eliminated retinoic acid-induced differentiation in this cell line. We developed a P19 embryonal carcinoma cell line that was deficient in the Na+/H+ antiporter. Na+/H+ exchanger-deficient cells were reduced in the rate of cell growth and this effect was enhanced by the removal of added HCO3- and by reducing extracellular pH. The antiporter-deficient cells were also markedly deficient in their ability to differentiate to neuronal-like cells and recovered this ability when the Na+/H+ antiporter was reintroduced. The results show that the absence of Na+/H+ antiport as a pH regulatory mechanism can result in deficiencies in both cell growth and differentiation in embryonal carcinoma cells.
Wang
H
H
Department of Pediatrics, Medical Research Council Group in the Molecular Biology of Membranes, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Singh
D
D
Fliegel
L
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D054278:Embryonal Carcinoma Stem Cells; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017923:Sodium-Hydrogen Exchangers; D014212:Tretinoin