β-arrestin is critical for early shear stress-induced Akt/eNOS activation in human vascular endothelial cells
β-arrestin is critical for early shear stress-induced Akt/eNOS activation in human vascular endothelial cells
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DOI：
10.1016/j.bbrc.2017.01.003
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发表时间：
2017-01-29
影响因子：
3.1
通讯作者：
Krieger, Jose Eduardo
中科院分区：
文献类型：
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作者：
Carneiro, Ana Paula;Fonseca-Alaniz, Miriam Helena;Krieger, Jose Eduardo
最近的证据表明，参与G蛋白偶联受体脱敏的β-拦阻素可能影响机械转导。在这里，我们观察到，在剪切力(SS，15dynes/cm2，10min)下，转染了针对β-arrestin 1和2的siRNA的人隐静脉内皮细胞(SVECs)中一氧化氮(NO)的产生被抑制。下调β-arrestins 1/2也可抑制SS诱导的Akt和内皮型一氧化氮合酶(eNOS，Serine 1177)磷酸化水平的升高。有趣的是，免疫沉淀显示β-arrestin与Akt、eNOS和小窝蛋白-1相互作用，这些相互作用不受SS的影响。我们的数据表明，Barrest ins和Akt/enos下游信号通路是SS诱导的早期SVECs产生NO所必需的，这与β-拦阻素和小窝蛋白-1是与细胞机械转导机制相关的预组装复合体的一部分的观点一致。(C)2017 Elsevier Inc.保留所有权利。
Recent evidence suggests that beta-arrestins, which are involved in G protein-coupled receptors desensitization, may influence mechanotransduction. Here, we observed that nitric oxide (NO) production was abrogated in human saphenous vein endothelial cells (SVECs) transfected with siRNA against beta-arrestin 1 and 2 subjected to shear stress (SS, 15 dynes/cm2, 10 min). The downregulation of beta-arrestins 1/2 in SVECs cells also prevented the SS-induced rise in levels of phosphorylation of Akt and endothelial nitric oxide synthase (eNOS, Serine 1177). Interestingly, immunoprecipitation revealed that beta-arrestin interacts with Akt, eNOS and caveolin-1 and these interactions are not influenced by SS. Our data indicate that barrestins and Akt/eNOS downstream signaling are required for early SS-induced NO production in SVECs, which is consistent with the idea that beta-arrestins and caveolin-1 are part of a pre-assembled complex associated with the cellular mechanotransduction machinery. (C) 2017 Elsevier Inc. All rights reserved.