Chitano Pasquale, Wang Lu, Mason Stanley N, Auten Richard L, Potts Erin N, Foster William M, Sturrock Anne, Kennedy Thomas P, Hoidal John R, Murphy Thomas M
Dept. of Pediatrics and Neonatal Perinatal Research Institute, Duke Univ. Medical Center, Rm. 302, Bell Bldg., Box 2994, Durham, NC 27710, USA.
Am J Physiol Lung Cell Mol Physiol. 2008 Jan;294(1):L139-48. doi: 10.1152/ajplung.00384.2007. Epub 2007 Nov 9.
NAD(P)H oxidase is one of the critical enzymes mediating cellular production of reactive oxygen species and has a central role in airway smooth muscle (ASM) cell proliferation. Since reactive oxygen species also affect ASM contractile response, we hypothesized a regulatory role of NAD(P)H oxidase in ASM contractility. We therefore studied ASM function in wild-type mice (C57BL/6J) and mice deficient in a component (p47phox) of NAD(P)H oxidase. In histological sections of the trachea, we found that the area occupied by ASM was 17% more in p47(phox-/-) than in wild-type mice. After correcting for the difference in ASM content, we found that force generation did not vary between the two genotypes. Similarly, their ASM shortening velocity, maximal power, and sensitivity to acetylcholine, as well as airway responsiveness to methacholine in vivo, were not significantly different. The main finding of this study was a significantly reduced ASM relaxation in p47phox-/- compared with wild-type mice both during the stimulus and after the end of stimulation. The tension relaxation attained at the 20th second of electric field stimulation was, respectively, 17.6 +/- 2.4 and 9.2 +/- 2.3% in null and wild-type mice (P <0.01 by t-test). Similar significant differences were found in the rate of tension relaxation and the time required to reduce tension by one-half. Our data suggest that NAD(P)H oxidase may have a role in the structural arrangement and mechanical properties of the airway tissue. Most importantly, we report the first evidence that the p47phox subunit of NAD(P)H oxidase plays a role in ASM relaxation.
NAD(P)H氧化酶是介导细胞产生活性氧的关键酶之一，在气道平滑肌（ASM）细胞增殖中起核心作用。由于活性氧也会影响ASM的收缩反应，我们推测NAD(P)H氧化酶在ASM收缩性中具有调节作用。因此，我们研究了野生型小鼠（C57BL/6J）和缺乏NAD(P)H氧化酶一个组分（p47phox）的小鼠的ASM功能。在气管组织切片中，我们发现p47(phox-/-)小鼠中ASM所占面积比野生型小鼠多17%。校正ASM含量差异后，我们发现两种基因型之间的力产生没有差异。同样，它们的ASM缩短速度、最大功率、对乙酰胆碱的敏感性以及体内气道对乙酰甲胆碱的反应性均无显著差异。本研究的主要发现是，与野生型小鼠相比，p47phox-/-小鼠在刺激期间和刺激结束后ASM松弛均显著降低。电场刺激第20秒时，基因敲除小鼠和野生型小鼠的张力松弛分别为17.6±2.4%和9.2±2.3%（t检验，P<0.01）。在张力松弛速率和张力减半所需时间方面也发现了类似的显著差异。我们的数据表明，NAD(P)H氧化酶可能在气道组织的结构排列和力学性能中起作用。最重要的是，我们首次报道了证据表明NAD(P)H氧化酶的p47phox亚基在ASM松弛中起作用。
