Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+.
Extracellular Na+ and initiation of DNA synthesis: role of intracellular pH and K+.
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DOI：
10.1083/jcb.98.3.1082
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发表时间：
1984-03
期刊：
影响因子：
--
通讯作者：
Rozengurt E
中科院分区：
文献类型：
--
作者：
Burns CP;Rozengurt E
启动的DNA合成在融合静止的3 T3细胞培养刺激表皮生长因子（EGF），血管加压素，胰岛素被废除，通过去除细胞外Na+。抑制是可逆的，时间和Na+浓度依赖性，而不是由于对125 I-EGF的结合或内化的影响。其他生长因子与不同的作用机制的组合刺激也受到影响，减少细胞外Na+，但不同的半最大Na+浓度。当胆碱被用作Na+的渗透替代品时，DNA合成的减少与细胞内K+的减少相关。相反，当使用蔗糖时，存在Na+-K+泵的刺激和细胞内K+的维持，这导致与胆碱相比在降低的细胞外Na+下的DNA合成速率略高。由表皮生长因子、血管加压素和胰岛素诱导的有丝分裂导致细胞质碱化，这通过增加弱酸性5，5-二甲基恶唑烷-2，4-二酮的摄取来确定。细胞外Na+的实验性减少阻断了这种细胞碱化。因此，在某些条件下，细胞外Na+的供应可能会限制细胞增殖，因为Na+/H+反向转运的Na+供应减少，导致碱化失败。我们得出结论，Na+流量和细胞内K和pH值的影响有一个重要的作用，在复杂的系统，调节增殖。
Initiation of DNA synthesis in confluent quiescent 3T3 cell cultures stimulated by epidermal growth factor (EGF), vasopressin, and insulin was abolished by removing extracellular Na+. The inhibition was reversible, time- and Na+-concentration-dependent, and not due to an effect on binding or internalization of 125I-EGF. Stimulation by combinations of other growth factors with different mechanisms of action was also affected by decreasing extracellular Na+, but with different half-maximal Na+ concentrations. When choline was used as an osmotic substitute for Na+, the decrease in DNA synthesis was correlated with the decrease in intracellular K+. In contrast, when sucrose was used there was stimulation of the Na+-K+ pump and maintenance of intracellular K+ that resulted in a somewhat higher rate of DNA synthesis at lowered extracellular Na+ compared to choline. Mitogenesis induced by epidermal growth factor, vasopressin, and insulin led to cytoplasmic alkalinization as determined by an increase in uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. Experimental decrease in extracellular Na+ blocked this cellular alkalinization. Therefore, under some conditions the supply of extracellular Na+ may limit cellular proliferation because of a reduction in the provision of Na+ to the Na+/H+ antiport and resultant failure of alkalinization. We conclude that Na+ flux and its effect on intracellular K and pH has a major role in the complex system that regulates proliferation.