TUMORIGENIC-3T3 CELLS MAINTAIN AN ALKALINE INTRACELLULAR PH UNDER PHYSIOLOGICAL CONDITIONS
TUMORIGENIC-3T3 CELLS MAINTAIN AN ALKALINE INTRACELLULAR PH UNDER PHYSIOLOGICAL CONDITIONS
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DOI：
10.1073/pnas.87.19.7414
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发表时间：
1990-10-01
影响因子：
11.1
通讯作者：
PERONA, R
中科院分区：
文献类型：
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作者：
GILLIES, RJ;MARTINEZZAGUILAN, R;PERONA, R
在哺乳动物细胞对有丝分裂原的反应中，最早的事件之一是Na+/H+交换的激活，其在不存在HCO 3-或外部pH值低于7.2的情况下增加细胞内pH（pHin）。增殖反应可以通过阻止pH值的增加而被阻断;然而，增殖反应不能通过用弱碱或高介质pH值人工提高pH值来刺激。这些观察结果支持了最佳pH值是增殖反应序列的必要但不充分的组成部分的假设。这一假说最近受到了质疑的观察，NIH 3 T3细胞与酵母H+-ATP酶转染使他们致瘤。虽然先前的测量表明，这些转染的细胞在没有HCO 3-的情况下保持较高的pH值，但H+-ATP酶转染是否在生理相关条件下升高pH值尚不清楚。目前的报告显示，这些转染细胞在HCO 3-存在下保持比对照细胞更高的pH，支持升高的pH是原位增殖触发的可能性。我们还表明，这些细胞是血清不依赖性的生长，他们糖酵解比表型正常的细胞快得多。
One of the earliest events in the response of mammalian cells to mitogens is activation of Na+/H+ exchange, which increases intracellular pH (pHin) in the absence of HCO3- or at external pH values below 7.2. The proliferative response can be blocked by preventing the pHin increase; yet, the proliferative response cannot be stimulated by artificially raising pHin with weak bases or high medium pH. These observayions support the hypothesis that optimal pHin is a necessary, but not sufficient, component of the proliferative-response sequence. This hypothesis has recently been challenged by the observation that transfection of NIH 3T3 cells with yeast H+-ATPase renders them tumorigenic. Although previous measurements indicated that these transfected cells maintain a higher pHin in the absence of HCO3-, whether H+-ATPase transfection raised the pHin under physiologically relevant conditions was not known. The current report shows that these transfected cells do maintain a higher pHin than control cells in the presence of HCO3-, supporting the possibility that elevated pHin is a proliferative trigger in situ. We also show that these cells are serum-independent for growth and that they glycolyze much more rapidly than phenotypically normal cells.