Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.3.1 (NADPH oxidase)
 11,281 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of the present study was to investigate the effects of advanced glycation end products (AGEs) modified protein on the permeability of endothelium monolayers and morphological changes of actin cytoskeleton. The roles of receptor for AGEs (RAGE), oxidant stress and the activation of p38 MAPK pathway in this pathological procedure were elucidated. Human umbilical vein endothelial cells (HUVECs)-derived cell line (ECV304) were incubated with AGEs modified human serum albumin (AGE-HSA) in concentrations of 12.5, 25, 50, and 100 microg/ml respectively, for 2, 4, 8, 12 and 24 h. As control, HSA of the same concentration was administered to cells. Then TRITC-albumin was added to evaluate Pa value that reflects the permeability of endothelial monolayer. Furthermore, to visualize the morphological changes of actin cytoskeleton, the treated cells were incubated with rhodamine-phalloidin to stain F-actin. The results showed that the trans-endothelial membrane flux of albumin was significantly increased in a concentration- and time-dependent manner upon the stimulation of AGE-HSA, accompanying with actin reorganization. The blockage of AGE and RAGE binding with anti-RAGE IgG and the pharmacological inhibition of NADPH oxidase or p38 MAP kinase greatly attenuated the AGE-induced hyperpermeability response, respectively. These results indicate that RAGE, NADPH oxidase and p38 MAPK are possibly involved in the mediation of AGEs-induced barrier dysfunction and actin cytoskeleton reorganization in endothelial cells.
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PMID:[Mechanism of advanced glycation end products-induced hyperpermeability in endothelial cells]. 1583 Jan 6

Glycated human serum albumin (Glc-HSA) has previously been reported (Higai K., et al., 2006) to induce E-selectin expression on human umbilical vein endothelial cells through activation of NADPH oxidase; however, Glc-HSA signaling in monocytes remains obscure. To clarify the influence on human monocyte-derived U937 cells, U937 cells were stimulated with Glc-HSA and glycoaldehyde-dimer-modified HSA (GA-HSA) for 2 h in the absence and presence of the protein kinase C (PKC) inhibitor calphostin and the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) and NADPH oxidase inhibitor apocynin; interleukin-8 (IL-8) mRNA expression was determined by RT-PCR. As a result, IL-8 mRNA expression in U-937 cells was time- and dose-dependently enhanced by stimulation with Glc-HSA and GA-HSA. Furthermore, promoter activity of the IL-8 reporter gene was enhanced approximately 2-fold by stimulation with Glc-HSA and GA-HSA. Nuclear factor kappaB (NFkappaB) and activator protein-1 (AP-1) reporter genes were also enhanced although CCAAT/enhancer binding protein (C/EBP) was not affected. IL-8 mRNA expression was suppressed by NAC and apocynin but not calphostin in cells stimulated with Glc-HSA; however, its expression in cells stimulated with GA-HSA was suppressed by calphostin but not NAC. These results indicated that IL-8 mRNA expression was upregulated by NFkappaB and AP-1 in U937 cells stimulated with Glc-HSA and GA-HSA, but the signaling pathways were different.
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PMID:Glycated human serum albumin induces interleukin 8 mRNA expression through reactive oxygen species and NADPH oxidase-dependent pathway in monocyte-derived U937 cells. 1791 46

The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.
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PMID:Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. 1857 17

Increased oxidative stress (OS) in diabetes mellitus is one of the major factors leading to diabetic pathology. However, the mediators and mechanism that provoke OS in diabetes is not fully understood, and it is possible that accumulation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions may incite circulating polymorphonuclear neutrophils (PMN) to generate reactive oxygen species (ROS). In this report, we aim to investigate the effect of AGE on reactive oxygen and nitrogen species generation and subsequent OS in PMN. AGE-HSA exert dose- and time-dependent enhancement of ROS and reactive nitrogen intermediates (RNI) generation by PMN. Increased ROS and RNI generation were found to be mediated through the upregulation of NADPH oxidase and inducible nitric oxide synthase (iNOS), respectively, as evident from the fact that AGE-treated neutrophils failed to generate ROS and RNI in presence of diphenyleneiodonium, a flavoprotein inhibitor for both enzymes. Further increased generation of ROS and RNI ceased when the cells were incubated with anti-RAGE antibody suggesting the involvement of AGE-RAGE interaction. Also increased malondialdehyde (MDA) and protein carbonyl formation in AGE-exposed PMN suggest induction of OS by AGE. This study provides evidence that AGEs may play a key role in the induction of oxidative stress through the augmentation of PMN-mediated ROS and RNI generation and this may be in part responsible for development of AGE-induced diabetic pathology.
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PMID:Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. 2204 12