TY - JOUR
T1 - Effect of Na+ flux inhibitors on induction of c‐fos, c‐myc, and ODC genes during cell cycle
AU - Panet, Rivka
AU - Amir, Iris
AU - Snyder, David
AU - Zonenshein, Leora
AU - Atlan, Henri
AU - Laskov, Reuven
AU - Panet, Amos
PY - 1989/7
Y1 - 1989/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0024380361&partnerID=8YFLogxK
U2 - 10.1002/jcp.1041400119
DO - 10.1002/jcp.1041400119
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C2 - 2472417
AN - SCOPUS:0024380361
SN - 0021-9541
VL - 140
SP - 161
EP - 168
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -