Role of Ca2+ in serum-stimulated Na+ influx in normal and transformed cells.
Role of Ca2+ in serum-stimulated Na+ influx in normal and transformed cells.
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Ca2 在正常细胞和转化细胞中血清刺激的 Na 内流中的作用。
DOI：
10.1152/ajpcell.1985.248.3.c288
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Villereal,ML
中科院分区：
文献类型：
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作者：
Owen,NE;Villereal,ML
以往对人包皮成纤维细胞的研究表明，血清刺激Na+内流的机制是通过钙-钙调蛋白介导的事件。在本实验中，细胞内钙离子拮抗剂8-(N，N-diethylamino)-octyl-3，4，5-trimethoxybenzoate，TMB-8)和钙调蛋白拮抗剂三氟拉嗪(TFP)均可阻断血清刺激的Na+内流[TMB-8浓度，半数抑制浓度(Ki)=15微米，TFP Ki=10微米]。在瑞士3T3细胞中也得到了类似的结果。相反，在转化的WI-38或Swiss 3T3细胞中，TMB-8和TFP对血清刺激的Na+内流没有任何影响(TMB-8Ki大于100微米，TFP Ki大于100微米)。此外，当测定正常细胞和转化细胞的45Ca~(2+)外流时，血清可显著刺激WI-38和Swiss 3T3细胞的45Ca~(2+)外流(P<0.05)，而对猴病毒40(SV40)-WI-38或SV40-Swiss 3T3细胞的45Ca~(2+)外流无影响。然而，细胞内钙离子的升高可以刺激Na+内流，因为A23187被发现在正常细胞和转化细胞中都能模拟血清的影响。这些结果表明，在转化的细胞中，被认为与血清刺激的正常细胞内Na+内流有关的钙-钙调蛋白介导的事件可能被绕过或覆盖。
Previous studies in human foreskin fibroblasts suggested that the mechanism by which serum stimulates Na+ influx is via a Ca2+-calmodulin-mediated event. In the present experiments in normal WI-38 cells (human lung fibroblasts), both the intracellular Ca2+ antagonist 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) and the potent calmodulin antagonist trifluoperazine (TFP) blocked serum-stimulated Na+ influx [TMB-8 concentration causing half-maximal inhibition (Ki) = 15 microM and TFP Ki = 10 microM]. Similar results were obtained in Swiss 3T3 cells. In contrast, in transformed WI-38 or Swiss 3T3 cells neither TMB-8 nor TFP had any effect on serum-stimulated Na+ influx (TMB-8 Ki greater than 100 microM and TFP Ki greater than 100 microM). In addition, when 45Ca2+ efflux measurements were made on normal and transformed cells, serum stimulated significant 45Ca2+ efflux (P less than 0.05) from WI-38 and Swiss 3T3 cells, while having no effect on 45Ca2+ efflux from simian virus 40 (SV40)-WI-38 or SV40-Swiss 3T3 cells. However, an elevation of intracellular Ca2+ can stimulate Na+ influx, since it was found that A23187 mimicked the effects of serum in both normal and transformed cells. These results suggest that the Ca2+-calmodulin-mediated event, which is thought to be involved in serum-stimulated Na+ influx in normal cells, may be bypassed or overridden in transformed cells.