)| PMID |
17046555 ( ) |
|---|---|
| Title | Activation of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase by advanced glycation end products links oxidative stress to altered retinal vascular endothelial growth factor expression. |
| Abstract | Increasing evidence indicates that advanced glycation end products (AGEs) promote retinal alterations through oxidative stress. However, the pathways involved in AGE-induced generation of reactive oxygen species (ROS) in retinal cells are poorly defined. In the present study, we investigated the role of nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase in AGE-induced ROS intracellular generation and vascular endothelial growth factor (VEGF) expression in bovine retinal endothelial cells (BRECs). Incubation of BRECs with 100 microg/mL AGEs increased ROS generation and VEGF expression in these cells. Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects. In retinal endothelial cells exposed to AGEs, translocation of protein kinase C (PKC)-beta2 and p47phox was observed. Inhibition of PKC by treatment of the cells with calphostin C, GF10923X, and LY379196 totally suppressed AGE-mediated p47phox translocation and ROS generation. Incubation of BRECs with gliclazide inhibited AGE-induced PKC-beta2 and p47phox translocation and totally abrogated AGE-mediated ROS generation and VEGF expression. Overall, these results demonstrate that AGEs induce intracellular ROS generation and VEGF expression in retinal endothelial cells through a PKC-dependent activation of NADPH oxidase. Inhibition of retinal NADPH oxidase expression and ROS generated by this system provides a new potential mechanism by which gliclazide may affect retinal VEGF expression and exert a beneficial effect on diabetic retinopathy. Department of Medicine, University of Montreal, Quebec, Canada H2L 4M1. |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 37 | p47phox | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 36 | nadph oxidase | |
| 12680 | VEGFA | vascular endothelial growth factor A | 31 | VEGF | vascular endothelial growth factor | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 4 | SOD | superoxide dismutase | |
| 399 | ALB | albumin | 3 | albumin | serum albumin | |
| 1516 | CAT | catalase | 3 | catalase | |
| 9393 | PRKCA | protein kinase C, alpha | 2 | protein kinase c | |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | 2 | endothelial cell growth factor | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | Nox2 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 1 | angiotensin ii | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22phox | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | AGE-induced ROS intracellular generation and vascular endothelial growth factor (VEGF) VEGF expression in bovine retinal endothelial cells (BRECs) BRECs |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | 100 _amp_#x3bc;g/mL _amp_#x3bc g mL AGEs increased ROS generation and VEGF expression in these cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | translocation of protein kinase C (PKC)-_amp_#x3b2;2 PKC -_amp_#x3b2 2 and p47phox was observed |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | cells with calphostin C GF10923X and LY379196 totally suppressed AGE-mediated p47phox translocation and ROS generation |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Incubation of BRECs with gliclazide inhibited AGE-induced PKC-_amp_#x3b2 2 and p47phox translocation and totally abrogated AGE-mediated ROS generation and VEGF expression |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | and p47phox translocation and totally abrogated AGE-mediated ROS generation and VEGF expression |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | these results demonstrate that AGEs induce intracellular ROS generation and VEGF expression in retinal endothelial cells through a PKC-dependent activation of |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | a new potential mechanism by which gliclazide may affect retinal VEGF expression and exert a beneficial effect on diabetic retinopathy |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | leukostasis cell death and apoptosis vascular endothelial growth factor (VEGF) VEGF expression and cell proliferation 7 8 9 10 11 and |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | role of NADPH oxidase activity in hypoxia-induced increases in retinal VEGF expression and neovascularization has been established 20 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | this enzyme in the stimulatory effect of AGEs on retinal VEGF expression 8 |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | a sulfonylurea with antioxidant properties 21 effectively inhibits AGE-induced retinal VEGF expression 8 we also evaluated the modulatory effect of this |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | ROS in BRECs and stimulate through PKC-dependent NADPH oxidase activation VEGF expression in these cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Antibody against p47phox was obtained from R_amp_#x26 D Systems (Minneapolis, Minneapolis MN |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | Polyclonal antibody to VEGF was purchased from Preprotech (Rock Rock Hill NJ |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Measurement of PKC-_amp_#x3b2 2 p47phox and VEGF protein expression |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | Measurement of PKC-_amp_#x3b2 2 p47phox and VEGF protein expression |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Cytosol and membrane PKC-_amp_#x3b2 2 expression membrane p47phox and VEGF expression were measured by Western blot analysis using |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | Cytosol and membrane PKC-_amp_#x3b2 2 expression membrane p47phox and VEGF expression were measured by Western blot analysis using specific antibodies |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Intracellular superoxide dismutase (SOD), SOD catalase and glutathione peroxidase activities were measured by using spectrophotometric |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | glucose had any significant effects on antioxidant enzyme activities (SOD, SOD catalase and glutathione peroxidase in BRECs (data data not shown |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | AGEs increase p47phox expression in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | stimuli that activate NADPH oxidase cause translocation of the cytosolic p47phox NADPH subunit 24 levels of p47phox protein in the membrane |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | translocation of the cytosolic p47phox NADPH subunit 24 levels of p47phox protein in the membrane fractions of AGE-stimulated BRECs were determined |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | g mL for 1 hour significantly increased the level of p47phox expression in the membrane fractions of these cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Translocation of p47phox was also observed in PMA-treated BRECs ( Fig 2 A |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | suggesting a role of PKC as an upstream kinase regulating p47phox in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | used as internal control was observed ( Fig 2 B p47phox protein levels normalized to the levels of _amp_#x3b2 -actin are |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Induction of p47phox expression in AGE-treated BRECs is PKC dependent |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | classical PKC inhibitors calphostin C and GF10923X respectively on AGE-induced p47phox translocation in BRECs was next assessed |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Incubation of BRECs with these agents totally abolished AGE-induced p47phox translocation in these cells ( Fig 3 A |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | used as internal control was observed ( Fig 3 B p47phox protein levels normalized to the levels of _amp_#x3b2 -actin are |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | NADPH oxidase mediates AGE-induced VEGF protein expression in BRECs |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | We previously documented that AGEs up-regulate VEGF expression in cultured BRECs through PKC activation and increased oxidative |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | next evaluated whether NADPH oxidase activation is required for AGE-induced VEGF expression in BRECs |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | the NADPH oxidase inhibitors apocynin or DPI totally suppresses AGE-induced VEGF expression in BRECs confirm this hypothesis 3.6 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Inhibitory effect of gliclazide on AGE-induced ROS generation and p47phox translocation in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | 2.5 _amp_#x3bc g/mL), g mL also totally abolished AGE-induced membrane p47phox protein expression ( Fig 6 B-a in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | used as internal control was observed ( Fig 6 B-b p47phox protein levels normalized to the levels of _amp_#x3b2 -actin are |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | NADPH oxidase in the ischemic retina has been associated with VEGF expression and neovascularization 20 and increased expression of this enzyme |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | and proliferation 7 and represents an important signaling component for VEGF 8 and retinal leukostasis 9 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | of NADPH by PKC is the PKC-dependent phosphorylation of the p47phox regulatory subunit and its translocation to the Nox2/p22phox Nox2 p22phox |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 1.0 | the p47phox regulatory subunit and its translocation to the Nox2/p22phox Nox2 p22phox heterodimer 24 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22phox | 0.3 | p47phox regulatory subunit and its translocation to the Nox2/p22phox Nox2 p22phox heterodimer 24 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | present study shows that exposure of BRECs to AGEs induces p47phox translocation and that PKC inhibitors abolish this effect |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | causal relationship has been established between phosphorylation and translocation of p47phox by PKC-_amp_#x3b2 and enhanced oxidative stress in diabetic vascular cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | the cells with the PKC-_amp_#x3b2 inhibitor LY379196 completely abolished AGE-induced p47phox translocation and ROS production |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | These data together with previous ones showing that translocation of p47phox by PKC-_amp_#x3b2 activation is required for ROS generation in diabetic |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | g/mL), g mL effectively inhibits intracellular production of ROS and p47phox expression in retinal endothelial cells identify NADPH oxidase as a |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | be achieved through inhibition of PKC-dependent phosphorylation and translocation of p47phox |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | have been reported to inhibit the phosphorylation and translocation of p47phox in vascular cells and inhibition of these molecular events have |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | VEGF is an important determinant of AGE-induced retinal vascular alterations |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | and in vivo studies have shown that AGEs induce retinal VEGF expression and convincing evidence has been provided for a role |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | NADPH oxidase inhibitors abolish the stimulatory effect of AGEs on VEGF expression in these cells demonstrate that activation of NADPH oxidase |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | of NADPH oxidase by AGEs links oxidant stress to retinal VEGF induction |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | with the observation that inhibition of NADPH oxidase activity blocks VEGF overexpression during ischemic retinopathy 20 clearly identify this enzyme as |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | Because neural cells primarily express VEGF in diabetic retinopathy 55 and 56 and show increased VEGF |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | VEGF in diabetic retinopathy 55 and 56 and show increased VEGF expression after acute exposure to exogenous AGEs 10 substantiation of |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | central role of NADPH oxidase in AGE-mediated ROS generation and VEGF induction in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Fig 2._amp_#xa0 Effect of AGEs on membrane p47phox protein levels in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Membrane p47phox (A) A and _amp_#x3b2 -actin (B) B protein levels were |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | (B) B protein levels were measured by Western blot analysis p47phox protein levels were normalized to the levels of _amp_#x3b2 -actin |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | Fig 3._amp_#xa0 Effect of PKC inhibitors on AGE-induced p47phox expression in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | At the end of these incubation periods membrane p47phox (A) A and _amp_#x3b2 -actin (B) B protein expression were |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | (B) B protein expression were measured by Western blot analysis p47phox protein levels were normalized to the levels of _amp_#x3b2 -actin |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | Fig 5._amp_#xa0 Role of NADPH oxidase in mediating AGE-induced VEGF expression in BRECs |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 6.8 | VEGF protein levels were normalized to the levels of _amp_#x3b2 -actin |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | 6._amp_#xa0 Inhibitory effect of gliclazide on AGE-induced ROS production and p47phox translocation in BRECs |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | At the end of this incubation period membrane p47phox (a) a and _amp_#x3b2 -actin (b) b protein levels were |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47phox | 6.1 | (b) b protein levels were measured by Western blot analysis p47phox protein levels were normalized to the levels of _amp_#x3b2 -actin |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the present study we investigated the role of nicotinamide adenine dinucleotide phosphate reduced form nadph oxidase in age induced ros intracellular generation and vascular endothelial growth factor vegf expression in bovine retinal endothelial cells brecs . |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | in the present study we investigated the role of nicotinamide adenine dinucleotide phosphate reduced form nadph oxidase in age induced ros intracellular generation and vascular endothelial growth factor vegf expression in bovine retinal endothelial cells brecs . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | treatment of the cells with the nadph oxidase inhibitors apocynin and diphenylene iodonium inhibited these effects. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | in retinal endothelial cells exposed to ages translocation of protein kinase c pkc _amp_#x3b2;2 and p47phox was observed. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | overall these results demonstrate that ages induce intracellular ros generation and vegf expression in retinal endothelial cells through a pkc dependent activation of nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | inhibition of retinal nadph oxidase expression and ros generated by this system provides a new potential mechanism by which gliclazide may affect retinal vegf expression and exert a beneficial effect on diabetic retinopathy. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | pathogenic mechanisms linking hyperglycemia with diabetic retinopathy include increased polyol pathway flux protein kinase c pkc activation and increased advanced glycation end product age formation [1] [2] [3] [4] [5] and [6] . |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | indeed we and others have demonstrated that ages promote through generation of oxidative stress retinal leukostasis cell death and apoptosis vascular endothelial growth factor vegf expression and cell proliferation [7] [8] [9] [10] [11] and [12] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | recently an important role of the nadph oxidase system in mediating increased retinal oxidative stress and complications in diabetes has been proposed. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in keeping with this it has been shown that pericytes do express a functional phagocyte type nadph oxidase which is up regulated by high glucose levels and a role of this enzyme in palmitate induced apoptosis of pericytes has been suggested [18] and [19] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | more importantly a role of nadph oxidase activity in hypoxia induced increases in retinal vegf expression and neovascularization has been established [20] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | our results demonstrate that ages increase nadph oxidase_amp_#x2013;driven ros in brecs and stimulate through pkc dependent nadph oxidase activation vegf expression in these cells. |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | endothelial cell growth factor | 1.0 | bovine endothelial cell growth factor was purchased from roche molecular biochemicals laval quebec canada . |
| 399 | ALB | albumin | serum albumin | 1.0 | plasma derived horse serum fibronectin 2_amp_#x2032; 7_amp_#x2032; dichlorodihydrofluorescein diacetate dcf da buthionine sulfoximine bso vitamin e immunoglobulin ig free bovine serum albumin bsa and phorbol myristate acetate pma a pkc activator were obtained from sigma st louis mo . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | gf109203x a selective inhibitor of classical pkc; calphostin c a pan specific pkc inhibitor; apocynin a selective nadph oxidase inhibitor; diphenylene iodonium dpi chloride an inhibitor of flavoprotein containing enzymes; and n acetylcysteine nac were obtained from calbiochem la jolla ca . |
| 399 | ALB | albumin | albumin | 1.0 | nonglycated albumin was obtained by incubating bsa in the same reaction mixture in the absence of glucose. |
| 3665 | FGF1 | fibroblast growth factor 1 (acidic) | endothelial cell growth factor | 1.0 | brecs were grown in endothelial basal medium supplemented with 10% plasma derived horse serum 3% fbs 50 _amp_#x3bc; g/ml heparin 50 _amp_#x3bc; g/ml bovine endothelial cell growth factor and 1% vol/vol penicillin streptomycin in fibronectin coated flasks 25 cm 2 at 37_amp_#xb0;c in 5% carbon dioxide/95% air atmosphere. |
| 1516 | CAT | catalase | catalase | 1.0 | measurement of superoxide dismutase catalase and glutathione peroxidase activities |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | measurement of superoxide dismutase catalase and glutathione peroxidase activities |
| 1516 | CAT | catalase | catalase | 1.0 | intracellular superoxide dismutase sod catalase and glutathione peroxidase activities were measured by using spectrophotometric analysis bioxytech sod 525 and catalase 520 kits portland or and colorimetic assay bioxytech gpx 340 kit respectively. 2.9. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | intracellular superoxide dismutase sod catalase and glutathione peroxidase activities were measured by using spectrophotometric analysis bioxytech sod 525 and catalase 520 kits portland or and colorimetic assay bioxytech gpx 340 kit r |
| 399 | ALB | albumin | albumin | 1.0 | treatment of brecs with ages 100 _amp_#x3bc; g/ml for 1 or 24 hours enhanced ros accumulation in these cells as compared with that observed with nonglycated albumin bsa fig 1 a ros production [% of control values]: age 1 hour 150 _amp_#xb1; 3 p _amp_#x3c; .01; age 24 hours 154 _amp_#xb1; 3 p _amp_#x3c; .01 . |
| 1516 | CAT | catalase | catalase | 1.0 | neither ages nor high glucose had any significant effects on antioxidant enzyme activities sod catalase and glutathione peroxidase in brecs data not shown . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | treatment of brecs with the nadph oxidase inhibitors apocynin or dpi chloride suppressed age induced ros production fig 1 b . 3.2. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | because stimuli that activate nadph oxidase cause translocation of the cytosolic p47phox nadph subunit [24] levels of p47phox protein in the membrane fractions of age stimulated brecs were determined next. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to further evaluate whether the nadph oxidase activation documented in brecs exposed to ages is pkc dependent the effect of the pan specific and selective classical pkc inhibitors calphostin c and gf10923x respectively on age induced p47phox tra |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a similar effect was observed when cells were treated with the selective pkc _amp_#x3b2; inhibitor ly379196 or with the nadph oxidase inhibitors apocynin or dpi fig 3 a . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to investigate whether activation of nadph oxidase by pkc and more specifically by the pkc _amp_#x3b2; isoform is involved in age induced ros accumulation in retinal endothelial cells brecs were pretreated for 1 hour with gf10923x calphostin c or ly3 |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase mediates age induced vegf protein expression in brecs |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | on the basis of our present results showing pkc dependent nadph oxidase activation in age treated brecs we next evaluated whether nadph oxidase activation is required for age induced vegf expression in brecs. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | data presented in fig. 5 which demonstrate that treatment of brecs with the nadph oxidase inhibitors apocynin or dpi totally suppresses age induced vegf expression in brecs confirm this hypothesis. 3.6. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | among the cellular sources of ros in the diabetic vascular system attention has been increasingly paid to nadph oxidase as the most important one [15] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | supporting the involvement of this multicomponent enzyme in the pathogenesis of diabetic vasculopathies increased nadph oxidase activity and subunit protein expression has been documented in vessels [16] [17] and [25] kidney [26] [27] [28] and [29] and retina [20] from diabetic animals and patients. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with an important role of nadph oxidase_amp_#x2013;driven ros production in the pathogenesis of diabetic retinopathy up regulation of nadph oxidase in the ischemic retina has been associated with vegf expression and neovascularization [20] and increased expression of this enzyme has been documented in cultured retinal cells exposed to a diabetic |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | recent findings have underscored the central role of nadph oxidase in age rage_amp_#x2013;mediated rage = receptor for age generation of ros in human umbilical vein endothelial cells [30] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in line with these results data generated in the present study demonstrate that activation of nadph oxidase mediates age induced enhancing oxidative stress in retinal endothelial cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in vascular cells exposed to high glucose levels a major consequence of pkc activation is the activation of nadph oxidase with subsequent ros production [37] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in diabetic vascular tissues pkc dependent activation of nadph oxidase can be amplified by various factors including high levels of glucose [18] [38] and [39] fatty acid [19] and angiotensin ii [18] and [40] . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | in diabetic vascular tissues pkc dependent activation of nadph oxidase can be amplified by various factors including high levels of glucose [18] [38] and [39] fatty acid [19] and angiotensin ii [18] and [40] . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | with the observation that both pkc and nadph inhibitors totally suppress age induced ros accumulation in brecs indicate that generation of oxidative stress in these cells occurs through pkc dependent nadph oxidase activation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | e that gliclazide at concentrations in the therapeutic range 5 to 10 _amp_#x3bc; g/ml effectively inhibits intracellular production of ros and p47phox expression in retinal endothelial cells identify nadph oxidase as a new key molecular target of this drug in retinal cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these results along with previous ones showing a similar effect of gliclazide on renal expression of nadph oxidase in diabetic rats [52] suggest a novel mechanism by which gliclazide may be effective in preventing diabetic vascular complications. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | our present data showing that ages induce nadph oxidase activation in cultured retinal endothelial cells and that nadph oxidase inhibitors abolish the stimulatory effect of ages on vegf expression in these cells demonstrate that activation of nadph oxidase by ages links oxidant stress to retinal vegf induction. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | inhibitors abolish the stimulatory effect of ages on vegf expression in these cells demonstrate that activation of nadph oxidase by ages links oxidant stress to retinal vegf induction. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these data along with the observation that inhibition of nadph oxidase activity blocks vegf overexpression during ischemic retinopathy [20] clearly identify this enzyme as one potential key target for the inhibition of the deleterious effect of ages in diabetic retinopa |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in summary the results of the present study demonstrate a central role of nadph oxidase in age mediated ros generation and vegf induction in brecs. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 1._amp_#xa0;effect of ages on ros generation in brecs: role of nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | b brecs were pretreated or not for 1 hour with the nadph oxidase inhibitors apocynin apo 10 _amp_#x3bc; m or dpi 10 _amp_#x3bc; m then incubated in the presence of ages 100 _amp_#x3bc; g/ml for a further 24 hour period with addition of 20 _amp_#x3bc; g/ml dcf da d |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | brecs were preincubated for 1 hour with the pkc inhibitors gf10923x gf 20 nmol/l calphostin c cal c 0.1 _amp_#x3bc; g/ml or ly379196 ly 30 nmol/l or with the nadph oxidase inhibitor apocynin apo 10 _amp_#x3bc; m or dpi 10 _amp_#x3bc; m before exposure to ages 100 _amp_#x3bc; g/ml for a further 1 hour period. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | fig. 5._amp_#xa0;role of nadph oxidase in mediating age induced vegf expression in brecs. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | brecs were preincubated for 1 hour with the nadph oxidase inhibitors apocynin apo 10 _amp_#x3bc; m or dpi 10 _amp_#x3bc; m before exposure to ages 100 _amp_#x3bc; g/ml for an additional 24 hour period. |