Wijcik L, Buchwald M, Riordan J R
Biochim Biophys Acta. 1979 Jul 4;585(3):374-82. doi: 10.1016/0304-4165(79)90081-3.
The membrane glycoprotein enzyme, alkaline phosphatase was induced in cultured human fibroblasts by dibutyryl cyclic AMP, sodium butyrate, the serum glycoprotein fetuin, the Tamm-Horsfall urinary glycoprotein, and by a number of inhibitors of DNA synthesis. The uninduced basal enzyme activity increased at later stages of growth when the cells became confluent. Induction by dibutyryl cyclic AMP or fetuin was most effective when the agents were added after the cells had reached stationary phase and was maximal after at least two days of exposure. The levels of induction resulting from the addition of pairs of the agents, dibutyryl cyclic AMP, n-butyrate and fetuin were additive indicating that these have different modes of action. The inhibitors of DNA synthesis, cytosine arabinoside, hydroxyurea, and methothrexate were less effective inducers. Bromodeoxyuridine which also has non-DNA mediated effects induced to the same extent as dibutyryl cyclic AMP. Similar experiments with sex- and age-matched cell strains derived from patients with cystic fibrosis failed to detect differences in the levels of induction from those observed in normal cells. In addition, the combined inductive effects of Tamm-Horsfall glycoprotein, isoproterenol and theophylline, were similar with normal and cystic fibrosis cells.
膜糖蛋白酶碱性磷酸酶可由二丁酰环磷酸腺苷、丁酸钠、血清糖蛋白胎球蛋白、Tamm-Horsfall尿糖蛋白以及多种DNA合成抑制剂在培养的人成纤维细胞中诱导产生。当细胞汇合时，未诱导的基础酶活性在生长后期增加。当细胞达到静止期后添加二丁酰环磷酸腺苷或胎球蛋白时诱导效果最佳，且在暴露至少两天后达到最大值。添加二丁酰环磷酸腺苷、正丁酸盐和胎球蛋白这几对试剂所产生的诱导水平是相加的，表明它们具有不同的作用方式。DNA合成抑制剂阿糖胞苷、羟基脲和甲氨蝶呤是效果较差的诱导剂。同样具有非DNA介导作用的溴脱氧尿苷诱导程度与二丁酰环磷酸腺苷相同。对来自囊性纤维化患者的性别和年龄匹配的细胞系进行的类似实验未能检测到与正常细胞中观察到的诱导水平存在差异。此外，Tamm-Horsfall糖蛋白、异丙肾上腺素和茶碱的联合诱导作用在正常细胞和囊性纤维化细胞中相似。
