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首页> 外文期刊>Calcified Tissue International >17β-Estradiol Rapidly Activates Calcium Release from Intracellular Stores via the GPR30 Pathway and MAPK Phosphorylation in Osteocyte-Like MLO-Y4 Cells
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17β-Estradiol Rapidly Activates Calcium Release from Intracellular Stores via the GPR30 Pathway and MAPK Phosphorylation in Osteocyte-Like MLO-Y4 Cells

机译:17β-雌二醇可通过GPR30途径快速激活钙从细胞内存储中的释放,并在像成骨细胞的MLO-Y4细胞中激活MAPK磷酸化

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摘要

Estrogen regulates critical cellular functions, and its deficiency initiates bone turnover and the development of bone mass loss in menopausal females. Recent studies have demonstrated that 17β-estradiol (E2) induces rapid non-genomic responses that activate downstream signaling molecules, thus providing a new perspective to understand the relationship between estrogen and bone metabolism. In this study, we investigated rapid estrogen responses, including calcium release and MAPK phosphorylation, in osteocyte-like MLO-Y4 cells. E2 elevated [Ca2+] i and increased Ca2+ oscillation frequency in a dose-dependent manner. Immunolabeling confirmed the expression of three estrogen receptors (ERα, ERβ, and G protein-coupled receptor 30 [GPR30]) in MLO-Y4 cells and localized GPR30 predominantly to the plasma membrane. E2 mobilized calcium from intracellular stores, and the use of selective agonist(s) for each ER showed that this was mediated mainly through the GPR30 pathway. MAPK phosphorylation increased in a biphasic manner, with peaks occurring after 7 and 60 min. GPR30 and classical ERs showed different temporal effects on MAPK phosphorylation and contributed to MAPK phosphorylation sequentially. ICI182,780 inhibited E2 activation of MAPK at 7 min, while the GPR30 agonist G-1 and antagonist G-15 failed to affect MAPK phosphorylation levels. G-1-mediated MAPK phosphorylation at 60 min was prevented by prior depletion of calcium stores. Our data suggest that E2 induces the non-genomic responses Ca2+ release and MAPK phosphorylation to regulate osteocyte function and indicate that multiple receptors mediate rapid E2 responses.
机译:雌激素调节关键的细胞功能,其缺乏引发更年期女性的骨转换和骨质流失的发展。最近的研究表明17β-雌二醇(E 2 )诱导快速的非基因组反应,激活下游信号分子,从而为了解雌激素与骨代谢之间的关系提供了新的视角。在这项研究中,我们调查了骨细胞样MLO-Y4细胞中的快速雌激素反应,包括钙释放和MAPK磷酸化。 E 2 以剂量依赖性方式升高[Ca 2 + ] i 并增加Ca 2 + 振荡频率。免疫标记法证实了MLO-Y4细胞中三种雌激素受体(ERα,ERβ和G蛋白偶联受体30 [GPR30])的表达,且GPR30主要定位于质膜。 E 2 从细胞内储存物中动员了钙,对每个ER使用选择性激动剂表明,这主要是通过GPR30途径介导的。 MAPK磷酸化以双相方式增加,在7和60分钟后出现峰。 GPR30和经典ERs对MAPK磷酸化表现出不同的时间效应,并依次促进MAPK磷酸化。 ICI182,780在7分钟时抑制MAPK的E 2 活化,而GPR30激动剂G-1和拮抗剂G-15不能影响MAPK磷酸化水平。在60分钟时,G-1介导的MAPK磷酸化被先前钙存储的消耗所阻止。我们的数据表明,E 2 诱导非基因组反应Ca 2 + 释放和MAPK磷酸化来调节骨细胞功能,并表明多个受体介导了快速的E 2 < / sub>响应。

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