Effect of Na+ flux inhibitors on induction of c‐fos, c‐myc, and ODC genes during cell cycle
- 1 July 1989
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 140 (1) , 161-168
- https://doi.org/10.1002/jcp.1041400119
Abstract
The role of Na + transport systems in the mitogenic signal induced by growth factors was studied, and it was shown that two Na + transport systems contribute to the early increase in cytoplasmic Na + in response to serum growth factors, namely the amiloride-sensitive Na+/H + antiport and the bumetanide-sensitive Na + /K + /CI- cotransport. Bumetanide or amiloride, when added separately, inhibited part of the increase in cytoplasmic Na +, as a response to the addition of serum to quiescent BALB/c mouse 3T3 fibroblasts. Each drug also suppressed part of the stimulation of the ouabain-sensitive Rb + influx, which was controlled by intracellular Na +. However, when both drugs were added together with serum growth factors, a complete inhibition of the early increase in [Na +], and subsequently a complete blockage of Na + /K + pump stimulation was obtained. Amiloride or bumetanide, when added separately, only partially inhibited DNA synthesis induced by serum, 24% and 8% respectively. However, when both drugs were added together, at the time of serum addition to the quiescent cells, cell entry into S-phase was completely inhibited. To investigate the mode of cell-cycle inhibition, analysis was done of the possible role of early Na + fluxes in the mitogenic signal transduced from cell membrane receptors to the nucleus. The effects of the two drugs amiloride and bumetanide on induction of three genes-c-fos, c-myc, and ornithin decarboxylase (ODC)-was measured during cell transition through the G1-phase. Amiloride and bumetanide, when added separately or in combination, did not inhibit the induction of c-fos, c-myc, and ODC mRNAs. These results suggest that stimulation of Na+ fluxes by serum growth factors is essential for cell transition into the S-phase of cell cycle, but it plays no apparent role in the growth factor signal transduced from the cell surface to the interior of the cell, as manifested by c-fos, c-myc, and ODC genes induction.This publication has 35 references indexed in Scilit:
- Stimulation of bumetanide‐sensitive K+ transport in Swiss 3T3 fibroblasts by serum and mitogenic hormonesJournal of Cellular Physiology, 1985
- Induction of c-fos gene and protein by growth factors precedes activation of c-mycNature, 1984
- Platelet-derived growth factor induces rapid but transient expression of the c-fos gene and proteinNature, 1984
- Characterization of potent sodium/proton exchange inhibitors from the amiloride series in A431 cellsBiochemistry, 1984
- Demonstration of a late amiloride‐sensitive event as a necessary step in initiation of DNA synthesis by thrombinJournal of Cellular Physiology, 1983
- Rb+ influxes differentiate between growth arrest of cells by different agentsThe Journal of Membrane Biology, 1983
- Differentiation between serum stimulation of ouabain-resistant and sensitive Rb influx in quiescent NIH 3T3 cellsThe Journal of Membrane Biology, 1982
- Intracellular univalent cations and the regulation of the BALB/c-3T3 cell cycle.The Journal of cell biology, 1981
- Na entry and Na‐K pump activity in murine, hamster, and human cells ‐ effect of monensin, serum, platelet extract, and viral transformationJournal of Cellular Physiology, 1980
- Potassium transport and content during G1 and S phase following serum stimulation of 3T3 cellsJournal of Cellular Physiology, 1977