Lagarde A E, Pouysségur J M
Cancer Biochem Biophys. 1986 Dec;9(1):1-14.
Several carriers mediate ionic fluxes across the plasma membrane in a variety of mammalian cell types. Intracellular proton concentration is regulated by virtue of the operation of at least two distinct systems: a stilbene-sensitive, Na+- dependent HCO3-/Cl- exchange system, and an amiloride-sensitive Na+/H+ antiporter. The contribution of these two transporters to the modulation of intracellular pH in response to either extracellular pH variations or cell stimulation by growth factors and tumor promoters has been studied in several cell lines, including fibroblast mutants lacking Na+/H+ antiport activity. The attainment of a permissive intracellular pH value is critical to the development of the mitogenic response elicited by growth factors. Kinetic studies have revealed particular features of the Na+/H+ antiporter that explain its function in the early sequence of biochemical events leading to DNA replication. The detailed investigation of the mechanisms by which protons and other ions might regulate cell proliferation has important implications for the understanding of the role of pH microenvironment in carcinogenesis, tumor development and chemotherapy.
几种载体介导多种哺乳动物细胞类型跨质膜的离子通量。细胞内质子浓度通过至少两种不同系统的运作来调节：一种对二苯乙烯敏感、依赖Na⁺的HCO₃⁻/Cl⁻交换系统，以及一种对氨氯吡咪敏感的Na⁺/H⁺反向转运体。在包括缺乏Na⁺/H⁺反向转运活性的成纤维细胞突变体在内的几种细胞系中，已经研究了这两种转运蛋白对细胞外pH变化或生长因子和肿瘤启动子刺激细胞时细胞内pH调节的贡献。达到允许的细胞内pH值对于生长因子引发的有丝分裂反应的发展至关重要。动力学研究揭示了Na⁺/H⁺反向转运体的特殊特征，可以解释其在导致DNA复制的生化事件早期序列中的作用。对质子和其他离子调节细胞增殖机制的详细研究，对于理解pH微环境在致癌作用、肿瘤发展和化疗中的作用具有重要意义。
