Brandes Ralf P, Miller Francis J, Beer Stefani, Haendeler Judith, Hoffmann Jörg, Ha Tulinh, Holland Steven M, Görlach Agnes, Busse Rudi
Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.
Free Radic Biol Med. 2002 Jun 1;32(11):1116-22. doi: 10.1016/s0891-5849(02)00789-x.
An NADPH oxidase is thought to be a main source of vascular superoxide (O(2)(-)) production. The functional role of this oxidase, however, and the contribution of the different subunits of the enzyme to cellular signaling are still incompletely understood. We determined the role of the p47phox subunit of the oxidase in O(2)(-) generation and signaling in aortic rings and cultured smooth muscle cells (SMC) from wild-type (WT) and p47phox-deficient (p47phox -/-) mice. Basal O(2)(-) levels in aortae of p47phox -/- mice were lower than those in WT aortae. Infusion of [val(5)]-angiotensin II increased O(2)(-) levels in aortae from WT more than in aortae from p47phox -/- mice. O(2)(-) generation was similar in quiescent SMC from WT and p47phox -/- mice. However, exposure to thrombin selectively increased O(2)(-) generation in VSMC from WT, but not from p47phox -/- mice. Thrombin-activated redox-mediated signal transduction and gene expression was attenuated in VSMC from p47phox -/- compared to cells from WT mice as determined by p38 MAP kinase activation and VEGF gene expression. We conclude that p47phox is important for vascular ROS production and redox-modulated signaling and gene expression in VSMC.
烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶被认为是血管超氧化物（O₂⁻）产生的主要来源。然而，这种氧化酶的功能作用以及该酶不同亚基对细胞信号传导的贡献仍未完全了解。我们确定了氧化酶的p47phox亚基在野生型（WT）和p47phox基因缺陷型（p47phox -/-）小鼠的主动脉环和培养的平滑肌细胞（SMC）中O₂⁻生成及信号传导中的作用。p47phox -/-小鼠主动脉中的基础O₂⁻水平低于WT小鼠主动脉。输注[缬氨酸⁵] - 血管紧张素II使WT小鼠主动脉中的O₂⁻水平升高幅度大于p47phox -/-小鼠主动脉。WT和p47phox -/-小鼠的静止SMC中的O₂⁻生成相似。然而，暴露于凝血酶可选择性地增加WT小鼠而非p47phox -/-小鼠的血管平滑肌细胞（VSMC）中的O₂⁻生成。与WT小鼠的细胞相比，p47phox -/-小鼠的VSMC中凝血酶激活的氧化还原介导的信号转导和基因表达减弱，这通过p38丝裂原活化蛋白激酶激活和血管内皮生长因子（VEGF）基因表达来确定。我们得出结论，p47phox对于VSMC中的血管活性氧生成以及氧化还原调节的信号传导和基因表达很重要。
