He Y, Suzuki T, Kashiwagi K, Igarashi K
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Biochem Biophys Res Commun. 1994 Aug 30;203(1):608-14. doi: 10.1006/bbrc.1994.2226.
Effects of antizyme on polyamine transport and spermine restoration of the growth of polyamine-deficient cells were examined by using mouse FM3A cells transfected with pMAMneoZ1 possessing rat antizyme cDNA under the control of glucocorticoid-inducible promoter. Treatments of the transfected cells with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC), and dexamethasone, an inducer of antizyme, both caused a decrease in ODC activity and polyamine contents and inhibition of cell growth. However, spermine uptake of the transfected cells was repressed by dexamethasone but stimulated by DFMO. The decrease in the rate of spermine uptake in dexamethasone-treated cells was attributed to an increase in Km value and a slight decrease in Vmax value. Accordingly, restoration of cell growth by spermine was less effective in dexamethasone-treated cells than DFMO-treated cells. These results clearly indicate that antizyme has dual functions: one for ODC degradation and the other for negative regulation of polyamine transport.
通过使用在糖皮质激素诱导型启动子控制下携带大鼠抗酶 cDNA 的 pMAMneoZ1 转染的小鼠 FM3A 细胞，研究了抗酶对多胺转运以及多胺缺乏细胞生长的精胺恢复作用的影响。用鸟氨酸脱羧酶（ODC）抑制剂α-二氟甲基鸟氨酸（DFMO）和抗酶诱导剂地塞米松处理转染细胞，均导致 ODC 活性和多胺含量降低以及细胞生长受到抑制。然而，转染细胞的精胺摄取被地塞米松抑制，但被 DFMO 刺激。地塞米松处理的细胞中精胺摄取速率的降低归因于 Km 值的增加和 Vmax 值的轻微降低。因此，与 DFMO 处理的细胞相比，精胺对地塞米松处理的细胞生长的恢复效果较差。这些结果清楚地表明抗酶具有双重功能：一种是用于 ODC 降解，另一种是用于多胺转运的负调控。
