Hoffmann Jörg, Dimmeler Stefanie, Haendeler Judith
Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
FEBS Lett. 2003 Sep 11;551(1-3):153-8. doi: 10.1016/s0014-5793(03)00917-7.
Laminar flow (shear stress) is an important stimulus for nitric oxide (NO) synthesis in endothelial cells. NO can react with free SH-groups of different proteins leading to S-nitrosylation. Since S-nitrosylation of proteins is an important regulator of protein functions, we investigated the effect of endogenously synthesized NO. Exposure to shear stress significantly increased the overall S-nitrosylation of proteins in endothelial cells. Interestingly, shear stress increased S-nitrosylation of specific target proteins, i.e. the catalytic p17 subunit of caspase-3, the GTPase p21ras and the oxidoreductase thioredoxin. S-nitrosylation resulted in an inhibition of caspase-3 and in an augmented activity of p21ras and thioredoxin. These data suggest that long term exposure to shear stress exerts its different atheroprotective effects at least in part via increased S-nitrosylation of specific signaling proteins.
层流（剪切应力）是内皮细胞中一氧化氮（NO）合成的重要刺激因素。NO可与不同蛋白质的游离巯基反应，导致蛋白质的S-亚硝基化。由于蛋白质的S-亚硝基化是蛋白质功能的重要调节因子，我们研究了内源性合成的NO的作用。暴露于剪切应力显著增加了内皮细胞中蛋白质的整体S-亚硝基化。有趣的是，剪切应力增加了特定靶蛋白的S-亚硝基化，即半胱天冬酶-3的催化p17亚基、GTP酶p21ras和氧化还原酶硫氧还蛋白。S-亚硝基化导致半胱天冬酶-3的抑制以及p21ras和硫氧还蛋白活性的增强。这些数据表明，长期暴露于剪切应力至少部分地通过增加特定信号蛋白的S-亚硝基化发挥其不同的抗动脉粥样硬化作用。
