Gosgnach W, Messika-Zeitoun D, Gonzalez W, Philipe M, Michel J B
Institut National de la Santé et de la Recherche Médicale Unit 460, Centre Hospitalier Universitaire Xavier Bichat, 75870 Paris cedex 18, France.
Am J Physiol Cell Physiol. 2000 Dec;279(6):C1880-8. doi: 10.1152/ajpcell.2000.279.6.C1880.
After deendothelialization, the most luminal smooth muscle cells of the neointima are in contact with blood flow and express inducible nitric oxide synthase (iNOS) in vivo. We hypothesized that shear stress may be a stimulus for this iNOS overexpression. We have thus submitted smooth muscle cells to laminar shear and measured the iNOS expression. Shear stress (20 dyn/cm(2)) induced iNOS mRNA and protein expression, whereas brain NOS mRNA expression was decreased. Conversely, nitrite production was increased. This production was blocked by a selective iNOS inhibitor. Pyrrolidine dithiocarbamate, an antioxidant molecule, and BXT-51072, a gluthation peroxidase mimic, both inhibited the shear-induced iNOS expression. Shear stress also increased the expression of both membrane subunits of NADPH oxidase p22(phox) and Mox-1. Shear stress activated the redox-sensitive nuclear translocation of the transcription nuclear factor-kappaB (NF-kappaB) and stimulated the degradation of both cytosolic inhibitors kappaB alpha and beta. These results show that shear stress can induce iNOS expression and nitrite production in smooth muscle cells and suggest that this regulation is probably mediated by oxidative stress-induced NF-kappaB activation.
在内皮剥脱后，新生内膜最内层的平滑肌细胞与血流接触，并在体内表达诱导型一氧化氮合酶（iNOS）。我们推测剪切应力可能是这种iNOS过表达的刺激因素。因此，我们使平滑肌细胞受到层流剪切，并测量iNOS的表达。剪切应力（20达因/平方厘米）诱导了iNOS mRNA和蛋白的表达，而脑NOS mRNA的表达则降低。相反，亚硝酸盐的生成增加。这种生成被一种选择性iNOS抑制剂所阻断。抗氧化分子吡咯烷二硫代氨基甲酸盐和谷胱甘肽过氧化物酶模拟物BXT-51072均抑制了剪切诱导的iNOS表达。剪切应力还增加了NADPH氧化酶p22（phox）和Mox-1两个膜亚基的表达。剪切应力激活了转录核因子-κB（NF-κB）的氧化还原敏感型核转位，并刺激了胞质抑制剂κBα和β的降解。这些结果表明，剪切应力可诱导平滑肌细胞中iNOS的表达和亚硝酸盐的生成，并提示这种调节可能是由氧化应激诱导的NF-κB激活介导的。
