Elevation of HeLa cell 3‐hydroxy‐3‐methylglutaryl coenzyme a reductase activity by glucocorticoids: Possible relationship to the cell cycle
Elevation of HeLa cell 3‐hydroxy‐3‐methylglutaryl coenzyme a reductase activity by glucocorticoids: Possible relationship to the cell cycle
复制标题
糖皮质激素提高 HeLa 细胞 3-羟基-3-甲基戊二酰辅酶 a 还原酶活性：与细胞周期的可能关系
DOI：
--
复制
发表时间：
1979
影响因子：
5.6
通讯作者：
G. Melnykovych
中科院分区：
文献类型：
--
作者：
W. Cavenee;G. Melnykovych
糖皮质激素对3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶，EC 1.1.1.34）活性的升高显示依赖于培养基中激素浓度（5 × 10−10至1 × 10−8 M），尽管在试验中存在10−5 M类固醇时未引起活性增加。地塞米松的添加具有时间依赖性，即，从血清去除后0小时到6小时，添加激素导致相同的峰值活性;在12小时添加激素导致略微升高，但导致峰值活性水平的延长维持;在24小时添加激素显示没有效果。当在上述时间加入放线菌酮时，随后的动力学表明，在6和24小时，对照和处理的培养物的酶活性衰减相同，但在12小时，地塞米松处理的细胞的活性在衰减开始前表现出延长的滞后，然后以与对照相同的速率进行。激素的持续存在对于继续诱导是不必要的，并且在激素存在下孵育的培养物中加入放线菌素D导致催化活性立即衰减而没有“超诱导”的证据。与地塞米松同时加入孕酮导致浓度依赖性抑制增强，表明糖皮质激素受体参与增强，表明糖皮质激素受体参与HMG-CoA还原酶活性升高。激素处理的细胞的流动显微荧光（FMF）分析表明延迟进入细胞周期的DNA合成（S）期。这种细胞周期扰动和HMG-CoA还原酶升高之间的时间关系进行了讨论。
Elevation of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase (HMG‐CoA reductase, EC 1.1.1.34) activity by glucocorticoids was shown to be dependent on the concentration of hormone in the medium over a range of 5 × 10−10 to 1 × 10−8 M, although the presence of steroid in the assay at 10−5 M elicited no increase in activity. There was a demonstrated time dependence for the addition of dexamethasone i.e., from zero to six hours after serum removal, addition of hormone resulted in the same peak activity; addition at 12 hours gave slight elevation but resulted in an extended maintenance of the peak level of activity; addition at 24 hours showed no effect. When cycloheximide was added at the above times, subsequent kinetics showed identical decay of the enzyme activities from control and treated cultures at 6 and 24 hours, but at 12 hours the activity from dexamethasone treated cells exhibited an extended lag before the onset of decay, which then proceeded at the same rate as the control. The continuous presence of the hormone was not necessary for the induction to continue and the addition of Actinomycin D to cultures incubated in the presence of hormone resulted in an immediate decay of catalytic activity without evidence of “superinduction”. The addition of progesterone at the same time as dexamethasone resulted in a concentration‐dependent inhibition of the augmentation, suggesting the involvement of the glucocorticoid receptor in the aug‐mentation, suggesting the involvement of the glucocorticoid receptor in the elevation of HMG‐CoA reductase activity. Flow microfluorometric (FMF) analysis of hormone treated cells indicated a delayed entrance into the DNA synthesis (S) phase of the cell cycle. The temporal relationships between this cell cycle perturbation and HMG‐CoA reductase elevation are discussed.