Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II
Localization of a constitutively active, phagocyte-like NADPH oxidase in rabbit aortic adventitia: Enhancement by angiotensin II
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DOI：
10.1073/pnas.94.26.14483
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发表时间：
1997-12-23
影响因子：
11.1
通讯作者：
Quinn, MT
中科院分区：
文献类型：
--
作者：
Pagano, PJ;Clark, JK;Quinn, MT
超氧阴离子（O-2(-)）在内源性抑制内皮源性一氧化氮（NO）的生物活性中起关键作用，并与高血压的发生有关。在先前的研究中，我们发现O-2（-）主要在离体兔主动脉外膜中产生，并作为NO的屏障。我们对负责外膜O-2（-）产生的酶进行了表征，并表明该酶是一种具有组成活性的NADPH氧化酶，其组成与吞噬细胞NADPH氧化酶相似。组成型O-2（-）生成活性定位于主动脉外膜成纤维细胞，并被强效血管收缩剂血管紧张素II增强。主动脉切片免疫组化显示，p22（phox）、gp91（phox）、p47（phox）和p67（phox）仅定位于兔主动脉外膜，与O-2（-）生成染色部位一致。p67（phox）的免疫缺失导致NADPH氧化酶活性的丧失，可以通过添加重组p67（phox）来恢复。进一步研究这种O-2（-）外来来源的调控对于阐明NO生物活性的调控机制具有重要意义，并可能有助于我们对高血压发病机制的理解。
Superoxide anion (O-2(-)) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated in the development of hypertension, In previous studies, we found that O-2(-) is produced predominantly in the adventitia of isolated rabbit aorta and acts as a barrier to NO, In the present studies, we characterize the enzyme responsible for O-2(-) production in the adventitia and show that this enzyme is a constitutively active NADPH oxidase with similar composition as the phagocyte NADPH oxidase. Constitutive O-2(-)-generating activity was localized to aortic adventitial fibroblasts and was enhanced by the potent vasoconstrictor angiotensin II, Immunohistochemistry of aortic sections demonstrated the presence of p22(phox), gp91(phox), p47(phox), and p67(phox) localized exclusively in rabbit aortic adventitia, coincident with the site of staining for O-2(-) production, Furthermore, immunodepletion of p67(phox) from adventitial fibroblast particulates resulted in the loss of NADPH oxidase activity, which could be restored by the addition of recombinant p67(phox). Further study into the regulation of this adventitial source of O-2(-) is important in elucidating the mechanisms regulating the bioactivity of NO and may contribute to our understanding of the pathogenesis of hypertension.