Activation of Na+/H+ exchange in cultured fibroblasts: synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors.
Activation of Na+/H+ exchange in cultured fibroblasts: synergism and antagonism between phorbol ester, Ca2+ ionophore, and growth factors.
复制标题
培养成纤维细胞中 Na /H 交换的激活：佛波酯、Ca2 离子载体和生长因子之间的协同和拮抗作用。
DOI：
10.1073/pnas.82.23.8053
复制
发表时间：
1985
影响因子：
11.1
通讯作者：
Villereal,ML
中科院分区：
文献类型：
--
作者：
Vicentini,LM;Villereal,ML
研究了蛋白激酶C激活剂佛波酯（PMA）对培养的人包皮成纤维细胞（HSWP细胞）Na+内流的影响。我们在这里报告，在血清剥夺HSWP细胞中，单独加入PMA对Na+内流没有显着影响。然而，加入PMA的细胞，其Na+/H+交换器部分激活的次最大剂量的Ca 2+离子载体A23187导致更大的刺激比单独使用A23187。这些数据表明，尽管蛋白激酶C的刺激不是激活HSWP细胞或另一种研究的人包皮细胞系（杰克逊成纤维细胞）中Na+/H+交换的足够信号，但蛋白激酶C激活与Ca 2+升高刺激Na+/H+交换存在一些协同效应。此外，我们发现PMA实际上抑制HSWP和杰克逊成纤维细胞中促分裂原诱导的Na+内流刺激。这一观察结果加强了以下论点：在这些细胞中，蛋白激酶C的激活不足以激活Na+/H+交换，并表明存在通过蛋白激酶C的负反馈控制，其抑制激活Na+/H+交换所必需的某些信号。然而，在HSWP细胞的观察相反，我们能够激活小鼠3 T3和人WI-38细胞与PMA单独的Na+/H+交换，这表明有一些不同的机制激活Na+/H+交换在不同类型的成纤维细胞。
The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C, on Na+ influx were investigated in cultured human foreskin fibroblasts (HSWP cells). We report here that in serum-deprived HSWP cells the addition of PMA alone has no significant effect on Na+ influx. However, the addition of PMA to cells whose Na+/H+ exchanger is partially activated with a submaximal dose of the Ca2+ ionophore A23187 leads to a larger stimulation than seen with A23187 alone. These data suggest that although stimulation of protein kinase C is not a sufficient signal to activate the Na+/H+ exchanger in HSWP cells or in another human foreskin line (Jackson fibroblasts) studied, there are some cooperative effects of protein kinase C activation with a rise in Ca2+ to stimulate Na+/H+ exchange. In addition, we found that PMA actually inhibits the mitogen-induced stimulation of Na+ influx in HSWP and Jackson fibroblasts. This observation strengthens the argument that in these cells activation of protein kinase C is not sufficient to activate Na+/H+ exchange and suggests that there is a negative feedback control via protein kinase C that inhibits some signal that is necessary for activating Na+/H+ exchange. However, in contrast to observations in HSWP cells, we were able to activate the Na+/H+ exchanger in mouse 3T3 and human WI-38 cells with PMA alone, suggesting that there is some diversity in the mechanism for activation of Na+/H+ exchange in different types of fibroblasts.