The leucocyte NADPH oxidase of neutrophils is a membrane-bound enzyme that catalyses the reduction of oxygen to O(-)(2) at the expense of NADPH. The enzyme is dormant in resting neutrophils but becomes active when the cells are exposed to the appropriate stimuli. During oxidase activation, the highly basic cytosolic oxidase component p47(phox) becomes phosphorylated on several serines and migra...

Macrophages play an important role in the pathogenesis of chronic inflammatory disease. Activation of these phagocytes induces the production of proinflammatory cytokines, such as IL-1 and TNFand the generation of reactive oxygen species (ROS), such as superoxide anion (O2 •–). Recently, we found that TNFtreatment of human monocytic cells (MonoMac1) and isolated human monocytes resulted in up-r...

Nitric oxide provokes vasodilation and inhibits platelet aggregation. We examined the effect of nitric oxide on superoxide anion production by three sources: activated intact neutrophils, xanthine oxidase/hypoxanthine, and the NADPH oxidase. Nitric oxide significantly inhibited the generation of superoxide anion by neutrophils exposed to either FMLP (10(-7)M) or PMA (150 ng/ml) (IC50 = 30 micro...

Chronic granulomatous disease (CGD) is characterized by inherited immune defects resulting from mutations in the NADPH oxidase complex genes. The X-linked type of CGD is caused by defects in the CYBB gene that encodes gp91-phox, a fundamental component of the NADPH oxidase complex. This mutation originates the most common and severe form of CGD, which typically has absence of NADPH oxidase func...

BACKGROUND AND PURPOSE One of the major contributors to brain injury after subarachnoid hemorrhage (SAH) is oxidative stress, and 1 of the major enzymatic sources of superoxide anion production in the brain is NADPH oxidase. Therefore, we studied whether hyperbaric oxygen (HBO) suppresses neuronal NADPH oxidase in a rat model of SAH. METHODS Eighty-three Sprague-Dawley male rats were assigned...

BACKGROUND/AIMS Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) ox...

Several studies have linked the production of reactive oxygen species (ROS) by the NADPH oxidase to cellular growth control. In many cases, activation of the NADPH oxidase and subsequent ROS generation is required for growth factor signaling and mitogenesis in nonimmune cells. In this study, we demonstrate that the transcriptional repressor HBP1 (HMG box-containing protein 1) regulates the gene...

BACKGROUND It has been reported that 20-hydroxyeicosatetraenoic acid (20-HETE) aggravates myocardial ischemia/reperfusion (I/R) injury, but the exact mechanism of action is still unclear. METHODS AND RESULTS Experiments were performed in isolated rat hearts subjected to 35 min of ischemia followed by 40 min of reperfusion in Langendorff preparations. Perfusion with HET0016, an inhibitor of 20...

Interactions of polymorphonuclear neutrophils (PMNs) with endothelial cells may contribute to the activation of endothelial cell responses involved in innate immunity. We explored a novel function of PMN NADPH oxidase in the mechanism of Toll-like receptor-2 (TLR2) upregulation induced by LPS-TLR4 signaling in endothelial cells. We showed that LPS induced TLR2 up-regulation through TLR4- and My...

Recent studies have indicated that lipid rafts (LRs) in the cell membrane are clustered in response to different stimuli to form signaling platforms for transmembrane transduction. It remains unknown whether this LR clustering participates in redox signaling in endothelial cells. The present study tested a hypothesis that clustering of LRs on the membrane of coronary endothelial cells produces ...