ROLE OF INTRACELLULAR PH IN MAMMALIAN CELL PROLIFERATION
ROLE OF INTRACELLULAR PH IN MAMMALIAN CELL PROLIFERATION
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DOI：
10.1159/000154638
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发表时间：
1992-01-01
影响因子：
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通讯作者：
PERONA P
中科院分区：
文献类型：
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作者：
GILLIES R J;MARTINEZ-ZAGUILAN R;PERONA P
哺乳动物细胞的细胞质 pH 值由 Na+/H+ 交换和 HCO3- 运输调节。在大多数增殖细胞中，这些系统协作将 pH1in 维持在允许生长的值范围内。在此范围内，其电离状态和活性受 pH 值影响的酶系统尚不清楚，但可能包括糖酵解、蛋白质合成和降解以及 DNA 合成机制。因此，适当的 pH 调节是增殖控制的必要但不充分的标准。另一方面，越来越多的证据表明 pH（和/或 DELTA..PSI.）“危机”可能对致癌作用很重要。体外致癌作用的至少两个不同阶段似乎具有不同的最适 pH 值（例如一种酸性，一种碱性）。一旦这些阶段过去，并且新的表型被表达，细胞对 pH 值变化的敏感性就会降低。可以通过用 H+-ATPase 转染来诱导最适碱性 pH 阶段。这导致细胞具有均质的次要表型特征，例如：糖酵解、pH、Ca2+、组成型 fos 表达和不依赖于 PDGF 的生长增加。此外，在天然肿瘤细胞的子集中观察到细胞表面 H+-ATP 酶的表达。
Cytoplasmic pH of mammalian cells is regulated by Na+/H+ exchange and HCO3- transport. In most proliferating cells, these systems collaborate to maintain pH1in within a window of values that are permissive for growth. The enzyme systems whose ionization states and activities are affected by pH in this range are not known, but can include glycolysis, protein synthesis and degradation, and the DNA synthetic machinery. Thus, proper regulation of pH is a necessary, but not sufficient, criterion for proliferative control. On the other hand, there is mounting evidence that pH (and/or .DELTA..PSI.) 'crises' might be important to carcinogenesis. At least two different stages of in vitro carcinogenesis appear to have distinct (e.g. one acidic, one alkaline) pH optima. Once these stages have been passed, and the new phenotype is expressed, cells exhibit a decreased sensitivity to pH changes. The stage with the alkaline pH optimum can be induced by transfection with a H+-ATPase. This results in cells with homogeneous secondary phenotypic characteristics, such as: increased glycolysis, pH, Ca2+, constitutive fos expression and PDGF-independent growth. Furthermore, expression of H+-ATPases on the cell surface is observed in a subset of naturally occurring tumor cells.