Airway smooth muscle relaxation is impaired in mice lacking the p47phox subunit of NAD(P)H oxidase.
Airway smooth muscle relaxation is impaired in mice lacking the p47phox subunit of NAD(P)H oxidase.
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缺乏 NAD(P)H 氧化酶 p47phox 亚基的小鼠气道平滑肌松弛受损。
DOI：
10.1152/ajplung.00384.2007
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Murphy,ThomasM
中科院分区：
文献类型：
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作者：
Chitano,Pasquale;Wang,Lu;Mason,StanleyN;Auten,RichardL;Potts,ErinN;Foster,WilliamM;Sturrock,Anne;Kennedy,ThomasP;Hoidal,JohnR;Murphy,ThomasM
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。由于活性氧也影响ASM的收缩反应，我们假设NAD（P）H氧化酶在ASM收缩中的调节作用。因此，我们研究了野生型小鼠（C57 BL/6 J）和NAD（P）H氧化酶的一种组分（p47 phox）缺陷小鼠的ASM功能。在气管的组织切片中，我们发现p47 phox −/−小鼠中ASM占据的面积比野生型小鼠多17%。在校正ASM含量的差异后，我们发现两种基因型之间的力生成没有变化。同样，他们的ASM缩短速度，最大功率，对乙酰胆碱的敏感性，以及气道反应性乙酰甲胆碱在体内，没有显着差异。这项研究的主要发现是在刺激期间和刺激结束后，与野生型小鼠相比，p47 phox −/−的ASM松弛显著减少。在电场刺激20秒时，null和野生型小鼠的张力松弛分别为17.6 ± 2.4%和9.2 ± 2.3%（P<0.01）。在张力松弛的速率和将张力减少一半所需的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机械性能中发挥作用。最重要的是，我们报告的第一个证据表明，p47 phox亚基的NAD（P）H氧化酶在ASM松弛中发挥作用。
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 p47phox−/−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 byt-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 p47phoxsubunit of NAD(P)H oxidase plays a role in ASM relaxation.