Shear stress-induced NO production is dependent on ATP autocrine signaling and capacitative calcium entry.
Shear stress-induced NO production is dependent on ATP autocrine signaling and capacitative calcium entry.
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DOI：
10.1007/s12195-014-0351-x
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发表时间：
2014-12-01
影响因子：
2.8
通讯作者：
Barbee, Kenneth A.
中科院分区：
文献类型：
--
作者：
Andrews, Allison M.;Jaron, Dov;Buerk, Donald G.;Barbee, Kenneth A.
血流诱导内皮细胞产生的一氧化氮（NO）在血管稳态中起着重要作用。然而，剪切应力激活NO产生的机制仍然不清楚，部分原因是测量NO的限制，特别是在流动条件下。剪切应力elixed ATP的释放，但自分泌刺激的ATP流动诱导的NO生产的相对贡献尚未建立。此外，钙在剪切应力诱导的NO产生中的重要性仍然存在争议，特别是电容性钙进入（CCE）的作用尚未确定。我们已经利用我们独特的NO测量装置来研究ATP自分泌信号和CCE在剪切应力诱导的NO产生中的作用。我们发现，内源性释放的ATP和下游激活的嘌呤受体和CCE在剪切应力诱导的NO产生中起着重要的作用。在静态条件下ATP诱导的eNOS磷酸化也依赖于CCE。抑制蛋白激酶C显著抑制eNOS磷酸化和钙反应。据我们所知，我们是第一个报告的作用，CCE在急性剪切应力诱导的NO反应的机制。此外，我们的工作突出了ATP自分泌信号在剪切应力诱导的NO产生的重要性。
Flow-induced production of nitric oxide (NO) by endothelial cells plays a fundamental role in vascular homeostasis. However, the mechanisms by which shear stress activates NO production remain unclear due in part to limitations in measuring NO, especially under flow conditions. Shear stress elicits the release of ATP, but the relative contribution of autocrine stimulation by ATP to flow-induced NO production has not been established. Furthermore, the importance of calcium in shear stress-induced NO production remains controversial, and in particular the role of capacitive calcium entry (CCE) has yet to be determined. We have utilized our unique NO measurement device to investigate the role of ATP autocrine signaling and CCE in shear stress-induced NO production. We found that endogenously released ATP and downstream activation of purinergic receptors and CCE plays a significant role in shear stress-induced NO production. ATP-induced eNOS phophorylation under static conditions is also dependent on CCE. Inhibition of protein kinase C significantly inhibited eNOS phosphorylation and the calcium response. To our knowledge, we are the first to report on the role of CCE in the mechanism of acute shear stress-induced NO response. In addition, our work highlights the importance of ATP autocrine signaling in shear stress-induced NO production.
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影响因子：
5.5
作者：
Dedkova, EN;Blatter, LA
通讯作者：
Blatter, LA
影响因子：
37.8
作者：
da Silva, Cleide Goncalves;Specht, Anke;Kaczmarek, Elzbieta
通讯作者：
Kaczmarek, Elzbieta
DOI：
10.1016/j.niox.2010.08.003
发表时间：
2010-12-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Andrews AM;Jaron D;Buerk DG;Kirby PL;Barbee KA
通讯作者：
Barbee KA
影响因子：
8.3
作者：
Silva, G;Beierwaltes, WH;Garvin, JL
通讯作者：
Garvin, JL
影响因子：
4.8
作者：
Boo, YC;Sorescu, G;Jo, HJ
通讯作者：
Jo, HJ