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首页> 外文期刊>American Journal of Physiology >Monovalent ions control proliferation of Ehrlich Lettre ascites cells
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Monovalent ions control proliferation of Ehrlich Lettre ascites cells

机译：单价离子控制Ehrlich Lettre腹水细胞的增殖

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摘要

Channels and transporters of monovalent ions are increasingly suggested as putative anticarcinogenic targets. However, the mechanisms involved in modulation of proliferation by monovalent ions are poorly understood. Here, we investigated the role of K +, Na +, and Cl - ions for the proliferation of Ehrlich Lettre ascites (ELA) cells. We measured the intracellular concentration of each ion in G 0, G 1, and S phases of the cell cycle following synchronization by serum starvation and release. We show that intracellular concentrations and content of Na + and Cl - were reduced in the G 0-G 1 phase transition, followed by an increased content of both ions in S phase concomitant with water uptake. The effect of substituting extracellular monovalent ions was investigated by bromodeoxyuridine incorporation and showed marked reduction after Na + and Cl - substitution. In spectrofluorometric measurements with the pH-sensitive dye BCECF, substitution of Na + was observed to upregulate the activity of the Na +/H + exchanger NHE1 as well as of Na +-independent acid extrusion mechanisms, facilitating intracellular pH (pH i) recovery after acid loading and increasing pH i. Results using the potential sensitive dye DiBaC 4(3) showed a reduced Cl - conductance in S compared with G 1 followed by transmembrane potential (E m) hyperpolarization in S. Cl - substitution by impermeable anions strongly inhibited proliferation and increased free, intracellular Ca 2+ ([Ca 2+] i), whereas a more permeable anion had little effect. Western blots showed reduced chloride intracellular channel CLIC1 and chloride channel ClC-2 expression in the plasma membrane in S compared with G 1. Our results suggest that Na + regulates ELA cell proliferation by regulating intracellular pH while Cl - may regulate proliferation by fine-tuning of E m in S phase and altered Ca 2+ signaling.
机译：一价离子的通道和转运体越来越多地被认为是公认的抗癌靶标。但是，对由单价离子调节增殖的机制了解甚少。在这里，我们研究了K +，Na +和Cl-离子在Ehrlich Lettre腹水（ELA）细胞增殖中的作用。我们通过血清饥饿和释放同步测量了细胞周期的G 0，G 1和S期中每个离子的细胞内浓度。我们表明，细胞内浓度和Na +和Cl-的含量在G 0-G 1相转变中降低，随后在S相中两个离子含量的增加与水的吸收有关。通过溴脱氧尿嘧啶核苷的掺入研究了取代细胞外单价离子的作用，并显示出Na +和Cl-取代后的明显减少。在使用pH敏感染料BCECF的荧光光谱法测量中，观察到Na +的取代可上调Na + / H +交换子NHE1的活性以及独立于Na +的酸挤出机制，从而促进细胞内pH（pH i）的恢复。加酸并增加pH值后i。使用电位敏感染料DiBaC 4（3）的结果显示，与G 1相比，S中的Cl导电性降低，随后S中的跨膜电位（E m）超极化。不可渗透的阴离子对Cl-的取代强烈抑制增殖并增加游离的细胞内Ca 2+（[Ca 2+] i），而更具渗透性的阴离子几乎没有影响。 Western印迹显示，与G 1相比，S中质膜中的氯离子细胞内通道CLIC1和氯离子通道ClC-2表达减少。 S期E m的变化和改变的Ca 2+信号传导。

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