NOX1 Membrane Protein Introduction

Introduction of NOX1

NOX1 gene product is a member of the NADPH oxidase family of enzymes. This family is associated with the catalytic one-electron transfer of oxygen to generate hydrogen peroxide or superoxide. There are two alternatively spliced transcript variants encoding multiple isoforms have been found for this gene: NOH1L and NOH1S. It has been reported that NOH1L may express in the uterus, prostate, colon carcinoma, and colon, but not in peripheral blood leukocytes. While NOH1S is only found in colon carcinoma and colon.

Function of NOX1 Membrane Protein

NADPH oxidase enzyme is a membrane protein with many subunits, one of which is NOX1. NOX1 has two isoforms with different tissue-specific expressions and dissimilar functions. As a voltage-gated proton channel, NOH1S regulates the H⁺ currents of resting phagocytes and other tissues. It plays a role in mediating the cellular pH, and the process can be interrupted by zinc. Different from NOH1S, NOH1L is a pyridine nucleotide-dependent oxidoreductase, and it contains an electron transport chain while NOH1S doesn’t have. NOH1L can generate superoxide and may be associated with H⁺ conducting through its electron transport chain. NOX1 has several cofactor binding sites, including NADP⁺ and FAD. The oxidase activity of NOX1 is mediated by NOXA1 and NOXO1. Diseases associated with NOX1 include Retinitis Pigmentosa 47 and Chronic Granulomatous Disease.

Fig.1 Interplay between NADPH oxidase and other sources of ROS. (Ray, 2005)

Application of NOX1 Membrane Protein in Literature

1. Bertram K., et al. NOX1 supports the metabolic remodeling of HepG2 cells. PLoS One. 2015, 10(3): e0122002. PubMed ID: 25806803
   
   

   This article reveals NOX1 is involved in the remodeling of hepatoblastoma cells metabolism towards a continuous production of building blocks which is required to keep a high rate of proliferation, suggesting that NOX1 might be a potential target for cancer therapy.

2. Sobey C.G., et al. NOX1 deficiency in apolipoprotein E-knockout mice is associated with elevated plasma lipids and enhanced atherosclerosis. Free Radic Res. 2015, 49(2): 186-98. PubMed ID: 25496431
   
   

   This article suggests that NOX1 may play a protective role in NOX1 against atherosclerosis and hyperlipidemia in APOE (-/-) mice, and further clarifies the distinct roles of different NOX isoforms in vascular pathology.

3. Hayes P., et al. Defects in NADPH Oxidase Genes NOX1 and DUOX2 in Very Early Onset Inflammatory Bowel Disease. Cell Mol Gastroenterol Hepatol. 2015, 1(5): 489-502. PubMed ID: 26301257
   
   

   This article confirms that the inactivating mutations in NOX1 contribute to the very early onset of inflammatory bowel disease (VEOIBD) by producing defective reactive oxygen species (ROS) in intestinal epithelial cells.

4. Streeter J., et al. Phosphorylation of Nox1 regulates association with NoxA1 activation domain. Circ Res. 2014, 115(11): 911-8. PubMed ID: 25228390
   
   

   This report demonstrates that Nox1 can be phosphorylated at threonine 429 by protein kinase C-beta1 through isothermal titration calorimetry and site-directed mutagenesis, and then facilitates the association of Nox1 with the NoxA1 activation domain, which is indispensable for the assembly of NADPH oxidase complex, production of reactive oxygen species, and migration of vascular smooth muscle cell.

5. Zhan M., et al. NOX1 mediates chemoresistance via HIF1α/MDR1 pathway in gallbladder cancer. Biochem Biophys Res Commun. 2015, 468(1-2): 79-85. PubMed ID: 26545779
   
   

   This article reveals that down-regulated NOX1 expression can lead to cisplatin efficiency in GBC-SD cells, whereas overexpression of which probably represses the sensitivity of cisplatin in SGC-996 cells.

NOX1 Preparation Options

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Reference

1. Ray R and Shah A M. (2005). NADPH oxidase and endothelial cell function. Clin Sci (Lond). 109(3): 217-26.

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