Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules.

Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules.
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内皮素通过降低 mRNA 分子的细胞内稳定性来下调 ETB 受体 mRNA 的水平。

DOI:
10.1016/s0006-291x(05)80813-7
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发表时间:
1992
影响因子:
3.1
通讯作者:
K. Goto
K. Goto
中科院分区:
生物学4区
文献类型:
--
作者:
T. Sakurai;H. Morimoto;Y. Kasuya;Y. Takuwa;H. Nakauchi;T. Masaki;K. Goto

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使用 ROS 17/2 大鼠骨肉瘤细胞作为模型系统,我们检查了内皮素 (ET) 诱导的 ETB 受体下调是否伴有 ETB 受体 mRNA 水平下降的可能性。 Northern印迹分析表明,低剂量的ET-1和ET-3导致细胞中ETBreceptor mRNA的短暂减少。 ETBreceptor mRNA 水平最大下降 (80%) 发生在细胞暴露于 ET 2∼-4 小时后,随后在 24 小时内逐渐恢复至对照水平。其作用具有剂量依赖性(EC50 ∼1 nM),ET-1 和 ET-3 在引发反应方面几乎是等价的。添加离子霉素(一种 Ca2+ 离子载体)或佛波醇二丁酸酯(一种蛋白激酶 C 激活剂)可模拟 ET 的效果。这些结果表明,ET 诱导的 ETB 受体 mRNA 下调是由 ETB 受体激活介导的,并且可能涉及 ETB 受体偶联的第二信使途径。我们还表明,ETBreceptor mRNA 具有较长的细胞内寿命,这表明 ET 诱导的 ETBreceptor mRNA 下调可能是由于 mRNA 稳定性降低,而不是 mRNA 转录失活。
Using ROS 17/2 rat osteosarcoma cells as a model system, we examined the possibility that endothelin (ET)-induced down-regulation of ETBreceptor was accompanied by a decrease in levels of ETBreceptor mRNA. Northern blot analysis showed that low doses of ET-1 and ET-3 caused a transient decrease in ETBreceptor mRNA in the cells. The maximum decrease in the levels of ETBreceptor mRNA (80 %) occurred after 2∼-4 h of exposure of the cells to ETs and was followed by a gradual recovery to control levels by 24 h. The effects were dose-dependent (EC50 ∼1 nM), and ET-1 and ET-3 were almost equipotent in eliciting the response. The addition of either ionomycin, a Ca2+ionophore, or phorbol dibutyrate, a protein kinase C activator, mimicked the effect of ETs. These results suggested that ETs-induced down-regulation of ETBreceptor mRNA was mediated by the activation of ETBreceptor and that it may have involved ETBreceptor coupled second messenger pathways. We also showed that ETBreceptor mRNA had a long intracellular life span which suggested that ETs-induced down-regulation of ETBreceptor mRNA may have been due to a decrease in the stability of mRNA, rather than inactivation of the transcription of mRNA.
DOI: --
发表时间: 1989
期刊: The Journal of biological chemistry
影响因子: --
作者:
J. Hadcock;H. Wang;C. Malbon
通讯作者: J. Hadcock;H. Wang;C. Malbon