Vairo G, Argyriou S, Bordun A M, Gonda T J, Cragoe E J, Hamilton J A
University of Melbourne, Department of Medicine, Parkville, Australia.
J Biol Chem. 1990 Oct 5;265(28):16929-39.
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.
生长因子激活Na⁺/H⁺交换被认为是有丝分裂的一个重要早期信号；然而，对于其在细胞周期后期的持续时间和需求却知之甚少。巨噬细胞特异性集落因子（CSF-1）能迅速激活小鼠骨髓来源巨噬细胞的Na⁺/H⁺交换，从而刺激Na⁺,K⁺-ATP酶活性。对CSF-1的反应至少维持24小时。用5-N,N-二甲基amiloride抑制Na⁺/H⁺交换可阻止CSF-1刺激的DNA合成和细胞生长。这不太可能是由于细胞质酸中毒，而更可能反映了对Na⁺/H⁺交换介导的Na⁺内流的需求。即使在生长因子作用8小时后添加DMA也会抑制S期进程。Na⁺/H⁺交换似乎不参与其他早期生长因子反应（c-fos和c-myc mRNA诱导以及一般RNA和蛋白质合成）的诱导。我们提出，细胞周期G1期后期生长因子刺激的Na⁺/H⁺交换是S期进程所必需的，但不是某些早期生长因子反应所必需的。
