一氧化氮对整合素αIIbβ3介导的血小板黏附及外向内信号传导的非环磷酸鸟苷依赖性抑制作用
cGMP-independent inhibition of integrin alphaIIbbeta3-mediated platelet adhesion and outside-in signalling by nitric oxide.
作者信息
Oberprieler Nikolaus G, Roberts Wayne, Riba Rocio, Graham Anne M, Homer-Vanniasinkam Shervanthi, Naseem Khalid M
机构信息
Centre for Atherothrombosis Research, Department of Medical Biosciences, University of Bradford, Richmond Building, Richmond Road, Bradford, West Yorkshire BD7 1DP, UK.
出版信息
FEBS Lett. 2007 Apr 3;581(7):1529-34. doi: 10.1016/j.febslet.2007.02.072. Epub 2007 Mar 7.
We examined the influence of S-nitrosoglutathione (GSNO) on alpha(IIb)beta(3) integrin-mediated platelet adhesion to immobilised fibrinogen. GSNO induced a time- and concentration-dependent inhibition of platelet adhesion. Inhibition was cGMP-independent and associated with both reduced platelet spreading and protein tyrosine phosphorylation. To investigate the cGMP-independent effects of NO we evaluated integrin beta(3) phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of beta(3) on tyrosines 773 and 785, which was reduced by GSNO in a cGMP independent manner. Similar results were observed in suspended platelets indicating that NO-induced effects were independent of spreading-induced signalling. This is the first demonstration that NO directly regulates integrin beta(3) phosphorylation.
我们研究了S-亚硝基谷胱甘肽（GSNO）对α（IIb）β（3）整合素介导的血小板与固定化纤维蛋白原黏附的影响。GSNO诱导了血小板黏附的时间和浓度依赖性抑制。抑制作用不依赖于环磷酸鸟苷（cGMP），且与血小板铺展减少和蛋白酪氨酸磷酸化有关。为了研究一氧化氮（NO）不依赖于cGMP的作用，我们评估了整合素β（3）的磷酸化。与纤维蛋白原的黏附诱导了β（3）在酪氨酸773和785处的快速磷酸化，而GSNO以不依赖于cGMP的方式降低了这种磷酸化。在悬浮血小板中也观察到了类似结果，表明NO诱导的效应不依赖于铺展诱导的信号传导。这是首次证明NO直接调节整合素β（3）的磷酸化。
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