Effects of dexamethasone and dibutyryl cyclic AMP on polyamine synthesizing enzymes in mouse lymphoma cells
Effects of dexamethasone and dibutyryl cyclic AMP on polyamine synthesizing enzymes in mouse lymphoma cells
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地塞米松和二丁酰环AMP对小鼠淋巴瘤细胞多胺合成酶的影响
DOI：
10.1002/jcp.1041060307
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发表时间：
1981
影响因子：
5.6
通讯作者：
U. Gehring
中科院分区：
文献类型：
--
作者：
Diane Handdock Russell;M. Haddox;U. Gehring
S49.1 当用 1 μM 地塞米松 (Dex) 或 0.5 mM N6, O2-二丁酰环腺苷 3′ :5′-单磷酸 (Bt2cAMP) 加 0.2 mM 茶碱处理时，淋巴瘤细胞停滞在细胞周期的 G1 期。然而，这两种药物对被捕获细胞内的多胺和环核苷酸代谢方面具有显着不同的影响。 Bt2cAMP 对鸟氨酸脱羧酶 (ODC) 活性具有早期且明显的抑制作用，导致 1 小时内降低至对照的 40%。然而，直到暴露 4 小时之前，Dex 处理的细胞中 ODC 活性没有显着抑制，此时 ODC 活性降低至对照值的约 60%。两种药物均可降低腺苷-L-甲硫氨酸脱羧酶 (SAMD) 活性，其中 Bt2cAMP 具有更明显的抑制作用。 Dex 10 小时后，SAMD 的活性降低至对照的 40%，而 Bt2cAMP 在 4 小时内将活性降低至对照的约 25%。在 Dex 处理的细胞中，细胞内多胺池迅速减少，但在暴露于 Bt2cAMP 的细胞中则没有。 Bt2cAMP 在 2 小时内将 I 型 (PKI) 和 II 型 (PKII) 环 AMP 依赖性蛋白激酶 (cAMP-PK) 活性降低至对照的 30% 或更少。相比之下，Dex 对 PKI 或 PKII 的影响非常小，直到 24 小时，此时细胞活力受到影响。在暴露于 Bt2cAMP 6 小时然后重悬于新鲜培养基中的细胞中，PKI 和 PKII 的比活性仍然显着降低。 ODC 活性对 Bt2cAMP 的响应迅速降低，并且洗脱后恢复缓慢，可能是由于总 PKI 和 PKII 活性显着降低。 Dex 对 PKI 和 PKII 比活性没有影响，仅缓慢抑制 ODC 活性，重悬于新鲜培养基中后酶活性快速恢复。这些数据进一步强调了维持细胞蛋白激酶库在调节响应天然类固醇和第二信使的生长抑制的恢复时间中的重要性。
S49.1 Lymphoma cells were arrested in G1 phase of the cell cycle when treated with either 1 μM dexamethasone (Dex) or 0.5 mM N6, O2‐dibutyryl cyclic adenosine 3′ :5′ ‐monophosphate (Bt2cAMP) plus 0.2 mM theophylline. However, the two agents had markedly different effects on aspects of polyamine and cyclic nucleotide metabolism within the arrested cells. Bt2cAMP had an early and pronounced inhibitory effect on ornithine decarboxylase (ODC) activity causing a decrease to 40% of control within 1 h. However, there was no significant inhibition of ODC activity in the Dex‐treated cells until 4 h of exposure, at which time ODC activity was reduced to approximately 60% of the control value. Sadenosyl‐L‐methionine decarboxylase (SAMD) activity was reduced by both agents, Bt2cAMP having the more pronounced inhibitory effect. The activity of SAMD was reduced to 40% of control after 10 h of Dex, whereas Bt2cAMP reduced the activity to approximately 25% of control within 4 h. Intracellular polyamine pools were decreased rapidly in Dex‐treated cells but not in those exposed to Bt2cAMP. Bt2cAMP decreased the amount of type I (PKI) and type II (PKII) cyclic AMP‐dependent protein kinase (cAMP‐PK) activity to 30% of control or less within 2 h. In contrast, Dex had very little effect on either PKI or PKII until 24 h, when cell viability was affected. The specific activity of both PKI and PKII remained significantly decreased in cells exposed to Bt2cAMP for 6 h and then resuspended in fresh medium. The rapid decrease in ODC activity in response to Bt2cAMP and the slow recovery after washout may be due to the marked decreases in total PKI and PKII activities. Dex, which had no effect on PKI and PKII specific activities, only slowly inhibited ODC activity and recovery of enzyme activity was rapid upon resuspension in fresh medium. These data further stress the importance of the maintenance of the cellular protein kinase pools in the regulation of the recovery time to growth inhibition in response to naturally occurring steroids and second messengers.