Boerner P, Saier M H
Department of Biology, University of California, San Diego, La Jolla 92093.
J Cell Physiol. 1988 Oct;137(1):117-24. doi: 10.1002/jcp.1041370114.
Neutral amino acid transport by system A was investigated in the epithelial cell lines MDCK and MDCK-T1. The latter line is a chemically induced, oncogenically transformed line derived from MDCK. Inducers of differentiation, sodium butyrate and 5-azacytidine, and a tumor promoter, TPA, were used as probes to delineate pathways of regulation involved in system A response to a variety of physiological conditions and agents. Azacytidine, an inhibitor of DNA methylation, and butyrate, an enhancer of histone acetylation, inhibited expression of system A, had little effect on system ASC, and slightly stimulated system L. Inhibition of system A expression by butyrate and azacytidine occurred under different conditions. Increases in system A activity due to amino acid starvation or transformation were inhibited by butyrate but not by azacytidine. Repressed system A activity, normally observed in the presence of high levels of amino acids, was more sensitive to azacytidine than to butyrate. The tumor promoter, TPA, stimulated system A activity in MDCK cells under normal growth conditions but did not stimulate activity in amino acid-starved MDCK cells or in MDCK-T1 cells. Stimulation of system A activity by TPA was prevented by prior exposure to butyrate but not to azacytidine. These results suggest 1) that system A expression observed in growing amino-acid-repressed MDCK cells is modulated by an azacytidine-sensitive mechanism and 2) that the elevated expression of system A activity induced by amino acid starvation, by chemical transformation to MDCK-T1, and by TPA is modulated by a butyrate-sensitive mechanism.
在MDCK和MDCK - T1上皮细胞系中研究了系统A介导的中性氨基酸转运。后者是源自MDCK的化学诱导致癌转化细胞系。使用分化诱导剂丁酸钠和5 -氮杂胞苷以及肿瘤促进剂TPA作为探针，来描绘系统A对各种生理条件和试剂反应中涉及的调节途径。DNA甲基化抑制剂氮杂胞苷和组蛋白乙酰化增强剂丁酸盐抑制系统A的表达，对系统ASC影响很小，并轻微刺激系统L。丁酸盐和氮杂胞苷对系统A表达的抑制在不同条件下发生。丁酸盐抑制了因氨基酸饥饿或转化导致的系统A活性增加，而氮杂胞苷则无此作用。通常在高浓度氨基酸存在下观察到的系统A活性受抑制状态，对氮杂胞苷比对丁酸盐更敏感。肿瘤促进剂TPA在正常生长条件下刺激MDCK细胞中的系统A活性，但在氨基酸饥饿的MDCK细胞或MDCK - T1细胞中不刺激其活性。预先暴露于丁酸盐可阻止TPA对系统A活性的刺激，而预先暴露于氮杂胞苷则无此作用。这些结果表明：1）在生长的氨基酸受抑制的MDCK细胞中观察到的系统A表达受一种对氮杂胞苷敏感的机制调节；2）由氨基酸饥饿、化学转化为MDCK - T1以及TPA诱导的系统A活性升高受一种对丁酸盐敏感的机制调节。
