Geiszt M, Kopp J B, Várnai P, Leto T L
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8010-4. doi: 10.1073/pnas.130135897.
Oxygen sensing is essential for homeostasis in all aerobic organisms, but its mechanism is poorly understood. Data suggest that a phagocytic-like NAD(P)H oxidase producing reactive oxygen species serves as a primary sensor for oxygen. We have characterized a source of superoxide anions in the kidney that we refer to as a renal NAD(P)H oxidase or Renox. Renox is homologous to gp91(phox) (91-kDa subunit of the phagocyte oxidase), the electron-transporting subunit of phagocytic NADPH oxidase, and contains all of the structural motifs considered essential for binding of heme, flavin, and nucleotide. In situ RNA hybridization revealed that renox is highly expressed at the site of erythropoietin production in the renal cortex, showing the greatest accumulation of renox mRNA in proximal convoluted tubule epithelial cells. NIH 3T3 fibroblasts overexpressing transfected Renox show increased production of superoxide and develop signs of cellular senescence. Our data suggest that Renox, as a renal source of reactive oxygen species, is a likely candidate for the oxygen sensor function regulating oxygen-dependent gene expression and may also have a role in the development of inflammatory processes in the kidney.
氧感应对于所有需氧生物的体内平衡至关重要，但其机制尚不清楚。数据表明，一种产生活性氧的吞噬样NAD(P)H氧化酶作为氧的主要传感器。我们已经鉴定出肾脏中一种超氧阴离子的来源，我们将其称为肾NAD(P)H氧化酶或Renox。Renox与gp91(phox)（吞噬细胞氧化酶的91 kDa亚基）同源，是吞噬性NADPH氧化酶的电子转运亚基，并且包含所有被认为对于血红素、黄素和核苷酸结合至关重要的结构基序。原位RNA杂交显示，renox在肾皮质促红细胞生成素产生部位高度表达，在近端小管上皮细胞中renox mRNA的积累最为显著。过表达转染Renox的NIH 3T3成纤维细胞显示超氧产生增加并出现细胞衰老迹象。我们的数据表明，Renox作为肾脏活性氧的来源，可能是调节氧依赖性基因表达的氧传感器功能的候选者，并且可能在肾脏炎症过程的发展中也起作用。
