NAD(P)H oxidase 1, a product of differentiated colon epithelial cells, can partially replace glycoprotein 91phox in the regulated production of superoxide by phagocytes.
نویسندگان
چکیده
Reactive oxygen species (ROS) serve several physiological functions; in some settings they act in host defense, while in others they function in cellular signaling or in biosynthetic reactions. We studied the expression and function of a recently described source of ROS, NAD(P)H oxidase 1 or Nox1, which has been associated with cell proliferation. In situ hybridization in mouse colon revealed high Nox1 expression within the lower two-thirds of colon crypts, where epithelial cells undergo proliferation and differentiation. Human multitumor tissue array analysis confirmed colon-specific Nox1 expression, predominantly in differentiated epithelial tumors. Differentiation of Caco2 and HT29 cells with 1alpha,25-dihydroxyvitamin D(3) or IFN-gamma enhances Nox1 expression and decreases cell proliferation, suggesting that Nox1 does not function as a mitogenic oxidase in colon epithelial cells. Transduction with retrovirus encoding Nox1 restored activation and differentiation-dependent superoxide production in gp91(phox)-deficient PLB-985 cells, indicating close functional similarities to the phagocyte oxidase (phox). Furthermore, coexpression of cytosolic components, p47(phox) and p67(phox), augments Nox1 activity in reconstituted K562 cells. Finally, Nox1 partially restores superoxide production in neutrophils differentiating ex vivo from gp91(phox)-deficient CD34(+) peripheral blood-derived stem cells derived from patients with X-linked chronic granulomatous disease. These studies demonstrate a significant functional homology (cofactor-dependent and activation-regulated superoxide production) between Nox1 and its closest homologue, gp91(phox), suggesting that targeted up-regulation of Nox1 expression in phagocytic cells could provide a novel approach in the molecular treatment of chronic granulomatous disease.
منابع مشابه
NAD(P)H Oxidase 1, a Product of Differentiated Colon Epithelial Cells, Can Partially Replace Glycoprotein 91 in the Regulated Production of Superoxide by Phagocytes
متن کامل
EPITHELIAL CELL BIOLOGY Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells
Background: Superoxide (O2) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells. Aims: To measure O2 production and effects of modulators of NAD(P)H oxidase activity and inhibitors of potential O2 generating enzymes i...
متن کاملSuperoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells.
BACKGROUND Superoxide (O(2)(-)) generation through the activity of reduced nicotinamide dinucleotide (NADH) or reduced nicotinamide dinucleotide phosphate (NADPH) oxidases has been demonstrated in a variety of cell types, but not in human colonic epithelial cells. AIMS To measure O(2)(-) production and effects of modulators of NAD(P)H oxidase activity and inhibitors of potential O(2)(-) gener...
متن کاملNutrient regulation of β cells NADPH - oxidase activity
In the presence of high glucose concentration (16.7 mM), pancreatic islets show increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). This activation may be a result of reactive oxygen species (ROS) stimulation, which is generated during glucose metabolism. NAD(P)H oxidase is mainly responsible for ROS production by phagocytic cells but its isoforms have been fo...
متن کاملNovel sources of reactive oxygen species in the human body.
There are several sources of reactive oxygen in the human body. Production of superoxide in mitochondria is a by-product of the function of the respiratory chain [1]. The first known example of regulated generation of reactive oxygen species (ROS) in mammalian cells was through the respiratory burst of phagocytic cells by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This enzyme ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 171 1 شماره
صفحات -
تاریخ انتشار 2003