The Na+:H+ antiport in cancer.
The Na+:H+ antiport in cancer.
复制标题
癌症中的 Na:H 反向转运。
DOI：
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发表时间：
1986
期刊：
影响因子：
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通讯作者：
Pouysségur Jm
中科院分区：
文献类型：
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作者：
Lagarde Ae;Pouysségur Jm
在多种哺乳动物细胞类型中，几种载体介导跨质膜的离子通量。细胞内质子浓度通过至少两个不同系统的运作来调节：一个是对苯乙烯敏感的Na+依赖的HCO3-/Cl-交换系统，另一个是对酰胺敏感的Na+/H+反转运体。在几种细胞系中，包括缺乏Na+/H+反端口活性的成纤维细胞突变体，研究了这两种转运蛋白对细胞内pH的调节作用，以响应细胞外pH变化或生长因子和肿瘤启动子的细胞刺激。获得容许的细胞内pH值对生长因子引起的有丝分裂反应的发展至关重要。动力学研究揭示了Na+/H+反转运蛋白的特殊特征，解释了其在导致DNA复制的生化事件的早期序列中的功能。详细研究质子和其他离子调控细胞增殖的机制，对于理解pH微环境在癌变、肿瘤发展和化疗中的作用具有重要意义。
: 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.