Homologs of gp91phox:: cloning and tissue expression of Nox3, Nox4, and Nox5
Homologs of gp91phox:: cloning and tissue expression of Nox3, Nox4, and Nox5
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DOI：
10.1016/s0378-1119(01)00449-8
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发表时间：
2001-05-16
期刊：
影响因子：
3.5
通讯作者：
Lambeth, JD
中科院分区：
文献类型：
--
作者：
Cheng, GJ;Cao, ZH;Lambeth, JD
gp 91 phox是呼吸爆发氧化酶的催化亚基，呼吸爆发氧化酶是一种存在于吞噬细胞中的NADPH依赖性超氧化物生成酶。在卵母细胞中，这种酶在宿主防御中起作用，但活性氧的产生也在各种非吞噬细胞中被描述，包括癌细胞。我们先前报道了Nox 1（NADPH氧化酶1）（gp 91 phox的同源物）的克隆，其在结肠和血管平滑肌中的表达，以及过表达时的致癌特性[Suh等人（1999）。Nature 401，79-82]。在这里，我们报告的克隆和组织表达的另外三个同源gp 91 phox，称为Nox 3。Nox 4和Nox 5是gp 91 phos同源物家族的成员。预测它们都编码约65 kDa的蛋白质，并且像gp 9 lphox一样，都显示出5-6个保守的预测的跨膜cr-螺旋，其含有推定的血红素结合区以及含有预测的FAD和NADPH结合位点的黄素蛋白同源结构域。Nox 3主要在胎儿组织中表达，Nox 4不仅在胎儿组织中表达，而且在肾、胎盘和胶质母细胞瘤细胞中表达。Nox 5在多种胎儿组织以及成人脾脏和子宫中表达。Nor亚型在几种来源于人类癌症的细胞中异常表达，Nox 4是研究的肿瘤细胞中最常表达的亚型。因此，Nor家族成员的表达可能解释了在非吞噬细胞中观察到的一些活性氧产生。(C)2001 Elsevier Science B. V.保留所有权利。
gp91phox is the catalytic subunit of the respiratory burst oxidase, an NADPH-dependent, superoxide generating enzyme present in phagocytes. In pha,oocytes, the enzyme functions in host defense, but reactive oxygen generation has also been described in a variety of non-phagocytic cells, including cancer cells. We previously reported the cloning of Nox1 (NADPH oxidase1), a homolog of gp91phox, its expression in colon and vascular smooth muscle, and its oncogenic properties when overexpressed [Suh et al. (1999). Nature 401, 79-82]. Herein, we report the cloning and tissue expression of three additional homologs of gp91phox, termed Nox3. Nox4 and Nox5, members of a growing family of gp91phos homologs. All are predicted to encode proteins of around 65 kDa, and like gp9lphox, all show 5-6 conserved predicted transmembrane cr-helices containing putative heme binding regions as well as a flavoprotein homology domain containing predicted binding sites for both FAD and NADPH. Nox3 is expressed primarily in fetal tissues, and Nox4 is expressed in not only fetal tissues, but also kidney, placenta and glioblastoma cells. Nox5 is expressed in a variety of fetal tissues as well as in adult spleen and uterus. Nor isoforms are aberrantly expressed in several cells derived from human cancers, with Nox4 being the isoform most frequently expressed in the tumor cells investigated. Thus, expression of Nor family members is likely to account for some of the reactive oxygen generation seen in non-phagocytic cells. (C) 2001 Elsevier Science B.V. All rights reserved.