Huang N N, Ahmed A H, Wang D J, Heppel L A
Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853.
Biochem Biophys Res Commun. 1992 Jan 31;182(2):836-43. doi: 10.1016/0006-291x(92)91808-4.
Using 3T3 and 3T6 mouse fibroblasts and A431 epidermoid carcinoma cells, we previously observed that extracellular ATP and ADP were mitogens and they synergized with other growth factors (Huang, N., Wang, D. and Heppel, L. A. (1989) Proc. Natl. Acad. Sci. USA 86, 7904-7908). We now report that ATP and ADP stimulated Na+ entry, intracellular alkalinization and Na+/K+ pump activity, which are early events that had been proposed to play a central role in DNA synthesis. In addition, ATP, ADP and AMPPNP stimulated uridine uptake by a pathway involving arachidonic acid metabolism. In A431 cells, activation of protein kinase C also contributed to ATP-dependent stimulation of uridine uptake. Concentrations of indomethacin and pertussis toxin which inhibited uridine uptake also blocked arachidonic acid metabolism and DNA synthesis. ATP acted as a competence factor. Interestingly, ATP did not have to be continuously present to stimulate uridine uptake. It was equally effective even when it was washed away after brief treatment of cells.
我们先前利用3T3和3T6小鼠成纤维细胞以及A431表皮癌细胞观察到，细胞外ATP和ADP是有丝分裂原，它们可与其他生长因子协同作用（黄，N.，王，D.和赫佩尔，L. A.（1989年）《美国国家科学院院刊》86，7904 - 7908）。我们现在报告，ATP和ADP刺激Na⁺内流、细胞内碱化以及Na⁺/K⁺泵活性，这些是早期事件，曾被认为在DNA合成中起核心作用。此外，ATP、ADP和AMPPNP通过涉及花生四烯酸代谢的途径刺激尿苷摄取。在A431细胞中，蛋白激酶C的激活也有助于ATP依赖性的尿苷摄取刺激。抑制尿苷摄取的吲哚美辛和百日咳毒素浓度也会阻断花生四烯酸代谢和DNA合成。ATP作为一种感受态因子。有趣的是，ATP不必持续存在就能刺激尿苷摄取。即使在对细胞进行短暂处理后将其洗去，它同样有效。
