Carneiro Ana Paula, Fonseca-Alaniz Miriam Helena, Dallan Luís Alberto Oliveira, Miyakawa Ayumi Aurea, Krieger Jose Eduardo
Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):75-81. doi: 10.1016/j.bbrc.2017.01.003. Epub 2017 Jan 4.
Recent evidence suggests that β-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 β-arrestin 1 and 2 subjected to shear stress (SS, 15 dynes/cm, 10 min). The downregulation of β-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 β-arrestin interacts with Akt, eNOS and caveolin-1 and these interactions are not influenced by SS. Our data indicate that β-arrestins and Akt/eNOS downstream signaling are required for early SS-induced NO production in SVECs, which is consistent with the idea that β-arrestins and caveolin-1 are part of a pre-assembled complex associated with the cellular mechanotransduction machinery.
最近的证据表明，参与G蛋白偶联受体脱敏的β-抑制蛋白可能影响机械转导。在此，我们观察到，在受到剪切应力（SS，15达因/平方厘米，10分钟）作用的人隐静脉内皮细胞（SVECs）中，转染针对β-抑制蛋白1和2的小干扰RNA（siRNA）后，一氧化氮（NO）的生成被消除。SVECs细胞中β-抑制蛋白1/2的下调也阻止了SS诱导的Akt和内皮型一氧化氮合酶（eNOS，丝氨酸1177）磷酸化水平的升高。有趣的是，免疫沉淀显示β-抑制蛋白与Akt、eNOS和小窝蛋白-1相互作用，且这些相互作用不受SS影响。我们的数据表明，β-抑制蛋白和Akt/eNOS下游信号传导是SVECs中早期SS诱导的NO生成所必需的，这与β-抑制蛋白和小窝蛋白-1是与细胞机械转导机制相关的预组装复合物的一部分这一观点一致。
