NADPH oxidase system

These stimuli elicit a complex series of responses that result in cell functions such as chemotaxis and release of inflammatory compounds, oxidants, and proteases. Probably related to chemotaxis is a rapid, transient actin polymerization response. Inflammation results in part from the release of proteases and myeloperoxidase normally stored in granules inside the cell (5) and from oxidants produced by an NADPH-oxidase system (6) located primarily... 

In this experiment FLPEP is the stimulus. When occupancy of new receptors is blocked by the addition of a formylpeptide receptor antagonist 30 s after stimulation (dashed line. Figure 8), the intracellular Ca remains elevated for 10 s, but then decays rapidly. The oxidant production rapidly plateaus. The first derivative of these data represent the time course of activation then turn-off of the NADPH oxidase system. The fact that Ca and oxidant production decay in concert may indicate that these events are linked in formylpeptide-stimulated cells. 

Mutations in the Genes for Components of the NADPH Oxidase System Cause Chronic Granulomatous Disease... 

The H2O2 used as substrate is generated by the NADPH oxidase system. CT is the halide usually employed, since it is present in relatively high concentration in plasma and body fluids. HOCI, the active ingredient of household liquid bleach, is a powerful oxidant and is highly microbicidal. When applied to normal tissues, its potential for causing damage is diminished be-... 

Oxygen is converted to the oxidizing agent superoxide anion (Oy) by cellular NADPH oxidase systems (prinicipally in phagocytes) and by xanthine oxidase (Figure 27.10). Hydrogen peroxide (H202) is formed by the further oxidation of Oy by superoxide dismutase (SOD) ... 

At least three different sources of ROS contribute to oxidative stress in the respiratory system. First, the initial inflammatory response involving macrophage-mediated phagocytosis involves the release of Oy, which is primarly generated by the NADPH oxidase system in these cells. This respiratory burst likely evolved as... 

An alternative source of the superoxide radical anion is leukocytic xanthine oxidase, acting in polymorphonuclear leukocytes of individuals with impairment of the NADPH oxidase system. Superoxide is one of the major metabolites produced in stimulated neutrophiles. Various estimations of Oj production yielded values ranging from 850 to 1350 p.mol/h/1010 cells (Bl, K16). 

The relative importance of the contribution of superoxide/hydrogen peroxide and hypochlorous acid in the bacterial killing mechanism is seen in patients with chronic granulomatous disease (CGD, with a defective NADPH-oxidase system), and those that are myeloperoxidase-deficient. CGD patients show persistent multiple infections especially in the skin, lungs, liver and bones by those bacterial strains whose killing by neutrophils requires oxygen. Individuals who are deficient in myeloperoxidase show no symptoms. 

NADPH-cytochrome P-450 reductase catalyzes the reduction of ferric ion to ferrous ion in the presence of chelators (384, 588). This reaction is similar to the peroxidation of microsomal lipids which has been shown to be dependent on the NADPH oxidase system of microsomes (389, 390). Lipid peroxidation is thought to be involved in prostaglandin biosynthesis (390-392). The microsomal system can be mimicked in the peroxidation of extracted microsomal lipid by a combination of NADPH, NADPH-cytochrome P-450 reductase, and ferric ion chelated with EDTA (374,... 

Other less-studied defense enzymes NADPH oxidase "system 2O2 + NADPH + H+ = 2O2 + NADP+... 

The inhibitory effects of berbamine and ISO natural products on the cytotoxic activity of polymorphonuclear leukocytes (PMN) was investigated. The research employed the effects of natural products on the PMN activation by the antitumor immunomodulator TAK (a linear P-1,3-D-glucan from Alcaligenes faecalis var. myxogenes) using a PMN cytotoxicity assay system. Berbamine was found to inhibit the activation of PMN activation by TAK, showing an IDJ0 33 pg/ml. From this, and related studies, it was postulated that berbamine may impair the NADPH oxidase system in the plasma membrane of PMN [199]. 

The reactive oxygen species production, stimulated by PMA, essentially due to the activity of NADPH oxidase system, was adopted as cellular functional character in human HL-60 cell line. R.O.S. metabolism was studied by CL assay as described. Assays were performed in triplicates at 25 °C. CL system contained in 1.00 mL final volume with modified KRP solution 100 nmoles luminol, 1 x 10 cells without treatment (control) or treated with ATRA or monomers, in presence or absence of... 

We then examined the inhibitory effects of nobiletin on differentiated HL-60 cells, known to generate 02 - with TPA stimulation and compared them with those of luteolin. As shown in Figure 6, nobiletin exhibited a much higher level of inhibition than luteolin, while the IC50 value of nobiletin (1.2 pM) was approximately 8 times lower than that of luteolin (9.8 pM). Because nobiletin did not significantly scavenge O2 generated from the xanthine/xanthine oxidase system nor inhibited xanthine oxidase activity up to a concenPation of 500 pM (data not shown), it may inhibit the assembly or activity of multicomponent NADPH oxidase system in differentiated HL-60 cells. 

In the induction of skin carcinogenesis, the phorbol ester PMA was used as a potent tumor promoter in mouse skin. A NADPH oxidase system of neutrophil is dominant for O2 generating in TPA-treated mouse skin (15). ROS from leukocytes, including 0, plays an important role for continuous and excessive production of chemotactic factors, leading to chronic inflammation and hyperplasia. 

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