Coordinated endothelial nitric oxide synthase activation by translocation and phosphorylation determines flow-induced nitric oxide production in resistance vessels.
Coordinated endothelial nitric oxide synthase activation by translocation and phosphorylation determines flow-induced nitric oxide production in resistance vessels.
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DOI：
10.1159/000355301
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发表时间：
2013
影响因子：
1.7
通讯作者：
Boric MP
中科院分区：
文献类型：
--
作者：
Figueroa XF;González DR;Puebla M;Acevedo JP;Rojas-Libano D;Durán WN;Boric MP
内皮型一氧化氮合酶（eNOS）与质膜上的小窝蛋白-1（Cav-1）结合。我们测试的假设，eNOS激活的剪切应力在阻力血管依赖于同步磷酸化，解离Cav-1和易位的膜结合酶的高尔基体和胞质溶胶。在隔离，灌注大鼠动脉肠系膜床，我们评估了流量的变化（2 - 10 mL/min）的影响，NO的生产，eNOS磷酸化丝氨酸1177，eNOS亚细胞分布和免疫共沉淀与Cav-1，在存在或不存在细胞外Ca2+。流量的增加诱导了NO产生的双相上升：在第一个15秒期间达到峰值的快速瞬态阶段（3 - 5分钟），随后是持续阶段，持续到刺激结束。与此同时，流动导致eNOS从微粒体区室快速转移到胞浆和高尔基体，同时eNOS磷酸化增加和eNOS-Cav-1结合减少。瞬时NO产生，eNOS易位，Cav-1的解离依赖于细胞外Ca 2+，而持续的NO产生被PI3K-Akt阻断剂渥曼青霉素所消除。在完整的阻力血管，流量的变化诱导NO生产的瞬时Ca2+依赖性eNOS易位从膜到细胞内室和持续的Ca2+非依赖性PI3K-Akt介导的磷酸化。
Endothelial nitric oxide synthase (eNOS) is associated with caveolin-1 (Cav-1) in plasma membrane. We tested the hypothesis that eNOS activation by shear stress in resistance vessels depends on synchronized phosphorylation, dissociation from Cav-1 and translocation of the membrane-bound enzyme to Golgi and cytosol. In isolated, perfused rat arterial mesenteric beds, we evaluated the effect of changes in flow rate (2–10 mL/min), on NO production, eNOS phosphorylation at serine 1177, eNOS subcellular distribution and co-immunoprecipitation with Cav-1, in the presence or absence of extracellular Ca2+. Increases in flow induced a biphasic rise in NO production: a rapid transient phase (3–5-min) that peaked during the first 15-sec, followed by a sustained phase, which lasted until the end of stimulation. Concomitantly, flow caused a rapid translocation of eNOS from the microsomal compartment to the cytosol and Golgi, paralleled by an increase in eNOS phosphorylation and a reduction in eNOS-Cav-1 association. Transient NO production, eNOS translocation, and dissociation from Cav-1 depended on extracellular Ca2+, while sustained NO production was abolished by the PI3K-Akt blocker wortmannin. In intact resistance vessels, changes in flow induce NO production by transient Ca2+-dependent eNOS translocation from membrane to intracellular compartments and sustained Ca2+-independent PI3K-Akt-mediated phosphorylation.
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影响因子：
64.8
作者：
Dimmeler, S;Fleming, I;Zeiher, AM
通讯作者：
Zeiher, AM
影响因子：
--
作者：
KUO, L;CHILIAN, WM;DAVIS, MJ
通讯作者：
DAVIS, MJ
影响因子：
4.8
作者：
Boo, YC;Sorescu, G;Jo, HJ
通讯作者：
Jo, HJ
影响因子：
5.5
作者：
Figueroa, XF;González, DR;Boric, MP
通讯作者：
Boric, MP
影响因子：
4.8
作者：
Fulton, D;Babbitt, R;Sessa, WC
通讯作者：
Sessa, WC