GLUTAMINE-SYNTHETASE INDUCTION BY GLUCOCORTICOIDS IN THE GLUCOCORTICOID-SENSITIVE HUMAN-LEUKEMIC CELL-LINE CEM-C7
GLUTAMINE-SYNTHETASE INDUCTION BY GLUCOCORTICOIDS IN THE GLUCOCORTICOID-SENSITIVE HUMAN-LEUKEMIC CELL-LINE CEM-C7
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DOI：
10.1002/jcp.1041100208
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发表时间：
1982-01-01
影响因子：
5.6
通讯作者：
THOMPSON, EB
中科院分区：
文献类型：
--
作者：
HARMON, JM;THOMPSON, EB
用糖皮质激素处理CEM-C7细胞产生酶谷氨酰胺合成酶（GS）活性的2.5倍增加。这种增加对于具有糖皮质激素活性的类固醇是特异性的，并且在与受体介导的机制一致的类固醇浓度范围内发生。地塞米松（dex）的半最大和最大诱导发生在2 × 10 - 6时。10- 8 M和2 ×10-7 Mdex，分别，浓度约等于那些必要的产生一半和完全占用糖皮质激素受体。GS活性在dex处理后1小时开始增加，到12小时完全增加。这是在dex对该细胞系的任何生长抑制或细胞溶解作用发生之前。这种增加依赖于糖皮质激素受体的存在，并需要RNA和蛋白质的合成。在刺激至最大水平后去除dex导致GS活性下降至诱导前水平，半衰期为5 h。谷氨酰胺剥夺细胞导致GS活性增加。即使在完全不存在谷氨酰胺的情况下，dex处理引起GS活性增加2.0-2.5倍，排除了谷氨酰胺摄取抑制作为dex诱导增加的机制。用5“-溴脱氧尿苷（BrdU）进行的实验表明，GS升高对BrdU取代DNA敏感，而dex诱导的生长抑制则不敏感。因此，GS升高和生长抑制在这个细胞系中似乎是独立表达的类固醇反应。
Treatment of CEM-C7 cells with glucocorticoids produces a 2.5-fold increase in the activity of the enzyme glutamine synthetase (GS.) This increase is specific for steroids with glucocorticoid activity and occurs over a range of steroid concentrations consistent with a receptor-mediated mechanism. Half-maximal and maximal inductions by dexamethasone (dex) occur at 2 .times. 10-8M and 2 .times. 10-7 M dex, respectively, concentrations approximately equal to those necessary to produce half and full occupancy of glucocorticoid receptors. GS activity began to increase 1 h after dex treatment and was complete by 12 h. This is well before any of the growth inhibitory or cytolytic effects of dex on this cell line occur. This increase was dependent on the presence of glucorticoid receptors and required both RNA and protein synthesis. Removal of dex following stimulation to maximal levels resulted in a decrease of GS activity to preinduced levels with a half-time of 5 h. Glutamine deprivation of cells resulted in increased GS activity. Even in the total absence of glutamine, dex treatment elicited a 2.0-2.5-fold increase in GS activity, ruling out inhibition of glutamine uptake as a mechanism for the dex-induced increase. Experiments with 5''-bromodeoxyuridine (BrdU) demonstrated that GS elevation was sensitive to BrdU substitution of DNA, while dex-induced growth inhibition was not. Therefore GS elevation and growth inhibition in this cell line appear to be independently expressed steroid responses.