)| PMID |
11287350 ( ) |
|---|---|
| Title | Activation of NADPH oxidase by AGE links oxidant stress to altered gene expression via RAGE. |
| Abstract | Engagement of the receptor for advanced glycation end products (RAGE) by products of nonenzymatic glycation/oxidation triggers the generation of reactive oxygen species (ROS), thereby altering gene expression. Because dissection of the precise events by which ROS are generated via RAGE is relevant to the pathogenesis of complications in AGE-related disorders, such as diabetes and renal failure, we tested the hypothesis that activation of NADPH oxidase contributed, at least in part, to enhancing oxidant stress via RAGE. Here we show that incubation of human endothelial cells with AGEs on the surface of diabetic red blood cells, or specific AGEs, (carboxymethyl)lysine (CML)-modified adducts, prompted intracellular generation of hydrogen peroxide, cell surface expression of vascular cell adhesion molecule-1, and generation of tissue factor in a manner suppressed by treatment with diphenyliodonium, but not by inhibitors of nitric oxide. Consistent with an important role for NADPH oxidase, although macrophages derived from wild-type mice expressed enhanced levels of tissue factor upon stimulation with AGE, macrophages derived from mice deficient in a central subunit of NADPH oxidase, gp91phox, failed to display enhanced tissue factor in the presence of AGE. These findings underscore a central role of NADPH oxidase in AGE-RAGE-mediated generation of ROS and provide a mechanism for altered gene expression in AGE-related disorders. Paris, France 75475. wautier@ints.fr |
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 |
|---|---|---|---|---|
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | 29 | vascular cell adhesion molecule 1 | VCAM-1 | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 21 | nadph oxidase | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 8 | SOD | superoxide dismutase | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 7 | NF-kB | NF-kappaB | |
| 1516 | CAT | catalase | 6 | catalase | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 5 | ERK | MAP | p38 | |
| 4983 | HMGB1 | high-mobility group box 1 | 4 | amphoterin | |
| 3528 | F10 | coagulation factor X | 4 | factor xa | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 4 | gp91phox-containing | gp91 phox | |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | 4 | p21 | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 2 | amyloid-induced | |
| 10486 | S100A1 | S100 calcium binding protein A1 | 2 | S100 | |
| 6204 | JUN | jun oncogene | 2 | c jun | c-Jun | |
| 19986 | CYCS | cytochrome c, somatic | 2 | cytochrome c | |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | 2 | p44 | |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 2 | NOS | |
| 21420 | CCRK | cell cycle related kinase | 1 | p42 | |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | 1 | heme oxygenase 1 | |
| 914 | B2M | beta-2-microglobulin | 1 | beta 2 microglobulin | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 1 | tumor necrosis factor alpha | |
| 12805 | XDH | xanthine dehydrogenase | 1 | xanthine oxidase | |
| 399 | ALB | albumin | 1 | albumin | |
| 4827 | HBB | hemoglobin, beta | 1 | hemoglobin | |
| 613 | APOE | apolipoprotein E | 1 | apolipoprotein e | |
| 6677 | LPL | lipoprotein lipase | 1 | lipoprotein lipase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 2.8 | from mice deficient in a central subunit of NADPH oxidase gp91phox failed to display enhanced tissue factor in the presence of |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | p21 | 0.3 | cascade of signal transduction events involving at least in part p21 p44/p42 p44 p42 mitogen-activated protein kinases and NF-kappaB ( 10 |
| 21420 | CCRK | cell cycle related kinase | p42 | 0.6 | transduction events involving at least in part p21 p44/p42 p44 p42 mitogen-activated protein kinases and NF-kappaB ( 10 13 21 50 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | in part p21 p44/p42 p44 p42 mitogen-activated protein kinases and NF-kappaB ( 10 13 21 50 56 |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | p44 | 0.4 | signal transduction events involving at least in part p21 p44/p42 p44 p42 mitogen-activated protein kinases and NF-kappaB ( 10 13 21 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | Specifically CML-mediated activation of NF-kappaB by CML-ovalbumin was markedly suppressed in DN-RAGE-transfected cells vs mock-transfected |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | TBARS increased mRNA for heme oxygenase-1 enhanced nuclear translocation of NF-kappaB and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | and increased endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) VCAM-1 and endothelial permeability ( 44 51 52 56 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 1.6 | this concept in vascular smooth muscle cells AGE-RAGE-mediated activation of ERK 1/2 1 2 kinases was enhanced in the presence of |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | p21 | 0.3 | demonstrated that ROIs generated in the cellular milieu directly activated p21 in those experiments the cysteine at position 118 was a |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | p21 | 0.3 | transduction pathways RAGE-bearing PC12 cells stably transfected to express mutant p21 in which Cys was mutated to a serine displayed complete |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 1.6 | mutated to a serine displayed complete suppression of activation of ERK 1/2 1 2 kinases upon exposure to AGE-albumin |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | ERK | 1.6 | In contrast AGE-mediated activation of ERK 1/2 1 2 kinases in PC12 cells overexpressing wild-type p21 |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | p21 | 0.3 | ERK 1/2 1 2 kinases in PC12 cells overexpressing wild-type p21 was intact ( 21 |
| 4827 | HBB | hemoglobin, beta | hemoglobin | 1.0 | The mean level of glycemia and %glycosylated hemoglobin observed in diabetic patients was 14.6 _amp_#177 3.3 mmol/l mmol |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Where indicated superoxide dismutase (SOD; SOD 300 U/ml; U ml Sigma catalase (100 100 U/ml; U |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | sRAGE (60 60 microg/ml), microg ml probucol (50 50 microM SOD (300 300 U/ml), U ml or catalase (100 100 U/ml) |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | Determination of VCAM-1 expression |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | with the indicated mediators for 16 h before determination of VCAM-1 expression |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | VCAM-1 expression was measured using mouse anti-human VCAM-1 IgG (R_amp_D R_amp_D |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | VCAM-1 expression was measured using mouse anti-human VCAM-1 IgG (R_amp_D R_amp_D Systems Abington Oxon UK |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kB | 0.3 | range of markers of oxidant stress including TBARS activation of NF-kB and induction of monolayer hyperpermeability all of these effects were |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | Antioxidants including catalase SOD probucol and NAC inhibited DRBC-mediated generation of ROI in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | However the antioxidants catalase and SOD were without significant effect on DRBC-mediated generation of intracellular H |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox-containing | 2.8 | Importantly recent studies indicating that endothelial cells express a gp91phox-containing NADPH oxidase ( 8 support our hypothesis that activation of |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.3 | to AGEs RAGE serves as a cell surface receptor for amyloid beta-peptide (A A beta a cleavage product of the beta-amyloid |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid-induced | 1.3 | of RAGE in a murine model of systemic amyloidosis suppressed amyloid-induced nuclear translocation of NF-kappaB and cellular activation ( 58 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | murine model of systemic amyloidosis suppressed amyloid-induced nuclear translocation of NF-kappaB and cellular activation ( 58 |
| 10486 | S100A1 | S100 calcium binding protein A1 | S100 | 1.3 | binding protein (ENRAGEs) ENRAGEs and related members of the S100/calgranulin S100 calgranulin family of proinflammatory cytokines ( 10 |
| 10486 | S100A1 | S100 calcium binding protein A1 | S100 | 1.3 | The S100/calgranulin S100 calgranulin family is comprised of closely related polypeptides released from |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | the inflammatory phenotype inhibition of RAGE-S100/calgranulin RAGE-S100 calgranulin interaction decreased NF-kappaB activation and expression of proinflammatory cytokines in tissues suggesting that |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 1.6 | signaling on amphoterin-coated matrices suppressed activation of p44/42, p44 42 p38 and stress-activated and c-Jun NH 2 -terminal protein kinases ( |
| 6204 | JUN | jun oncogene | c-Jun | 1.3 | suppressed activation of p44/42, p44 42 p38 and stress-activated and c-Jun NH 2 -terminal protein kinases ( 50 |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | p44 | 0.2 | RAGE RAGE signaling on amphoterin-coated matrices suppressed activation of p44/42, p44 42 p38 and stress-activated and c-Jun NH 2 -terminal protein |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 1.6 | In this context one consequence of ligand-RAGE-mediated activation of MAP kinases and NF-kappaB is increased transcription and translation of VCAM-1 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.3 | context one consequence of ligand-RAGE-mediated activation of MAP kinases and NF-kappaB is increased transcription and translation of VCAM-1 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | MAP kinases and NF-kappaB is increased transcription and translation of VCAM-1 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | adhesion of proinflammatory mononuclear cells at least in part via VCAM-1 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | Recent studies have suggested that the proinflammatory effects of VCAM-1 are not limited to cellular adhesion events as binding of |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | limited to cellular adhesion events as binding of ligand to VCAM-1 in endothelial cell lines and primary cultures induced activation of |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | NADPH oxidase and a range of proinflammatory mediators such as VCAM-1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | products (sRAGE; sRAGE 60 microg/ml), microg ml superoxide dismutase (SOD; SOD 300 U/ml), U ml catalase (100 100 U/ml), U ml |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | 60 microg/ml), microg ml catalase (100 100 U/ml), U ml SOD (300 300 U/ml), U ml probucol (50 50 microM diphenyliodonium |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | enhances cell surface expression of vascular cell adhesion molecule-1 (VCAM-1) VCAM-1 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | VCAM-1 expression was measured using mouse anti-human VCAM-1 Ig and binding |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | VCAM-1 expression was measured using mouse anti-human VCAM-1 Ig and binding was revealed with a second antibody I-labeled |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91phox | 2.8 | Thioglycollate-elicited MPs were retrieved from mice deficient in gp91phox or wild-type C57BL/6J C57BL 6J mice |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | patients with diabetes resulted in increased transcription and translation of VCAM-1 ( 44 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | resulted in an 1.8-fold increase in cell surface expression of VCAM-1 (Fig Fig 2 A |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | these events was demonstrated by suppression of DRBC-mediated induction of VCAM-1 in the presence of sRAGE (Fig Fig 2 A |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | was the finding that marked suppression of DRBC-mediated expression of VCAM-1 resulted in the presence of DPI (Fig Fig 2 A |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | indicate that the effects of DPI on DRBC-mediated expression of VCAM-1 were dose dependent |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | Compared with induction of VCAM-1 by DRBC in the absence of DPI (2.73 2.73 _amp_#177 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | microM resulted in an 90% reduction in specific activity for VCAM-1 (0.359 0.359 _amp_#177 0.035 cpm _amp_#215 10 P _lt_ 0.001 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | Compared with induction of VCAM-1 by DRBC in the absence of DPI treatment with DPI |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | microM resulted in an 70% reduction in specific activity for VCAM-1 (0.814 0.814 _amp_#177 0.105 cpm _amp_#215 10 P _lt_ 0.01 |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | (0.5 0.5 microM an 50% reduction in specific activity for VCAM-1 was noted 1.355 _amp_#177 0.15 x 10 counts/min counts min |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | (0.25 0.25 microM an 24% reduction in specific activity for VCAM-1 was noted (2.105 2.105 _amp_#177 0.32 cpm _amp_#215 10 P |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | In contrast blockade of NO synthase (NOS) NOS with L -NMMA had no effect (Fig Fig 2 A |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | resulted in a significant increase in cell surface expression of VCAM-1 (Fig Fig 2 B |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | DRBC or CML-modified adducts did not affect basal expression of VCAM-1 in these studies (data data not shown |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 0.9 | In contrast blockade of NOS with L -NMMA had no effect (Fig Fig 3 |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ise events by which ros are generated via rage is relevant to the pathogenesis of complications in age related disorders such as diabetes and renal failure we tested the hypothesis that activation of nadph oxidase contributed at least in part to enhancing oxidant stress via rage. |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | cells with ages on the surface of diabetic red blood cells or specific ages carboxymethyl lysine cml modified adducts prompted intracellular generation of hydrogen peroxide cell surface expression of vascular cell adhesion molecule 1 and generation of tissue factor in a manner suppressed by treatment with diphenyliodonium but not by inhibitors of nitric oxide. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with an important role for nadph oxidase although macrophages derived from wild type mice expressed enhanced levels of tissue factor upon stimulation with age macrophages derived from mice deficient in a central subunit of nadph oxidase gp9 |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although macrophages derived from wild type mice expressed enhanced levels of tissue factor upon stimulation with age macrophages derived from mice deficient in a central subunit of nadph oxidase gp91phox failed to display enhanced tissue factor in the presence of age. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings underscore a central role of nadph oxidase in age rage mediated generation of ros and provide a mechanism for altered gene expression in age related disorders. |
| 914 | B2M | beta-2-microglobulin | beta 2 microglobulin | 1.0 | a key consequence of the interaction of ages either those prepared in vitro such as age or cml modified adducts of proteins or those formed endogenously in vivo such as age beta 2 microglobulin ages formed on the surface of diabetic red blood cells or ages immunoisolated from the serum of patients with diabetes or renal failure with rage is the generation of reactive oxygen intermediates ro |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | raction resulted in generation of thiobarbituric acid reactive substances tbars increased mrna for heme oxygenase 1 enhanced nuclear translocation of nf kappab and increased endothelial expression of vascular cell adhesion molecule 1 vcam 1 and endothelial permeability 44 51 52 56 . |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | heme oxygenase 1 | 1.0 | in vitro and/or in vivo age rage interaction resulted in generation of thiobarbituric acid reactive substances tbars increased mrna for heme oxygenase 1 enhanced nuclear translocation of nf kappab and increased endothelial expression of vascular cell adhesion molecule 1 vcam 1 and endothelial permeability 44 51 52 56 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | here we tested the hypothesis that activation of nadph oxidase by age rage interaction contributed at least in part to the generation of rois and initiation of a cascade of signal transduction events leading to altered gene expression in the cellular microenviro |
| 1516 | CAT | catalase | catalase | 1.0 | where indicated superoxide dismutase sod; 300 u/ml; sigma catalase 100 u/ml; sigma probucol 50 microm; sigma or n acetylcysteine nac; 0.03 m; sigma was added to the incubation buffer. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | where indicated superoxide dismutase sod; 300 u/ml; sigma catalase 100 u/ml; sigma probucol 50 microm; sigma or n acetylcysteine nac; 0.03 m; sigma was added to the incubation buffer. |
| 1516 | CAT | catalase | catalase | 1.0 | iators were co incubated with diphenyliodonium chloride 31 dpi; 5 microm; alexis san diego ca n monomethyl l arginine l nmma; 0.001 m; alexis rat srage 60 microg/ml probucol 50 microm sod 300 u/ml or catalase 100 u/ml . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | confluent huvec in 35 mm plastic dishes were incubated in phenol free medium 199 0.5 ml; life technologies containing cytochrome c 160 microm; sigma . |
| 19986 | CYCS | cytochrome c, somatic | cytochrome c | 1.0 | tion of superoxide in nanomoles was calculated as d absorbance at 550 nm _amp_#215; 100 /6.3 where d absorbance is calculated as the difference between the absorbance of reduced and oxidized forms of cytochrome c . |
| 3528 | F10 | coagulation factor X | factor xa | 1.0 | procoagulant activity was assessed by an amydolytic assay using a factor xa specific chromogenic substrate cbs 31 39 stago asni_amp_egrave;res france according to previously published methods 36 . |
| 3528 | F10 | coagulation factor X | factor xa | 1.0 | for each plate a standard curve from 0 to 1 mu of purified human factor xa/well was established. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | male gp91 phox null mice backcrossed 11 generations into the c57bl/6 background were a generous gift from dr. mary dinauer indiana university school of medicine indianapolis in 17 35 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to test the concept that nadph oxidase was a central target of age rage interaction in the cellular milieu by which rois were generated within the cell we studied the effects of ages on rage bearing huvec and in vivo derived murine macrop |
| 1516 | CAT | catalase | catalase | 1.0 | antioxidants including catalase sod probucol and nac inhibited drbc mediated generation of roi in the extracellular milieu fig 1 a . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these effects of drbc were inhibited in the presence of srage and by dpi the latter strongly suggestive of a role for nadph oxidase in generation of intracellular roi fig 1 b . |
| 1516 | CAT | catalase | catalase | 1.0 | however the antioxidants catalase and sod were without significant effect on drbc mediated generation of intracellular h 2 o 2 consistent with their inability to penetrate living cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings highlight the contribution of a specific pathway activation of nadph oxidase by which age mediated generation of rois and triggering of signal transduction events lead to altered gene expression in ec and macrophages via rage. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although dpi may inhibit other flavoprotein dehydrogenases in addition to nadph oxidase 26 31 our observations that hmap another inhibitor of nadph oxidase 42 similarly suppresses age mediated generation of rois and the finding that enhanced activity of tf in age stimulated macrophages retrieved from gp91 null mice was suppressed compared with wild type |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | f rois and the finding that enhanced activity of tf in age stimulated macrophages retrieved from gp91 null mice was suppressed compared with wild type macrophages strongly suggest important roles for nadph oxidase in age mediated processes. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | importantly recent studies indicating that endothelial cells express a gp91phox containing nadph oxidase 8 support our hypothesis that activation of this enzyme provides a source of roi upon age engagement of rage in ec. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 8 it was shown that nadph oxidase was a major source of roi generation in the arterial wall because its activation was associated with impaired bioavailability of endothelium derived no. |
| 4983 | HMGB1 | high-mobility group box 1 | amphoterin | 1.0 | previous studies further indicated that rage was likely a receptor for amphoterin a molecule linked to neurite outgrowth in developing neurons of the central and peripheral nervous system 12 . |
| 4983 | HMGB1 | high-mobility group box 1 | amphoterin | 1.0 | these studies suggested that amphoterin rage was linked to cellular migration and invasiveness. |
| 4983 | HMGB1 | high-mobility group box 1 | amphoterin | 1.0 | consistent with this concept the expression of amphoterin and rage is increased in murine and human tumors. |
| 4983 | HMGB1 | high-mobility group box 1 | amphoterin | 1.0 | consistent with an important role for rage mediated signal transduction in these processes blockade of rage/rage signaling on amphoterin coated matrices suppressed activation of p44/42 p38 and stress activated and c jun nh 2 terminal protein kinases 50 . |
| 6204 | JUN | jun oncogene | c jun | 1.0 | h an important role for rage mediated signal transduction in these processes blockade of rage/rage signaling on amphoterin coated matrices suppressed activation of p44/42 p38 and stress activated and c jun nh 2 terminal protein kinases 50 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor alpha | 1.0 | at the cell surface endothelium stimulated by a range of mediators such as lipoprotein lipase tumor necrosis factor alpha ages and enrages for example displays increased adhesion of proinflammatory mononuclear cells at least in part via vcam 1. |
| 6677 | LPL | lipoprotein lipase | lipoprotein lipase | 1.0 | at the cell surface endothelium stimulated by a range of mediators such as lipoprotein lipase tumor necrosis factor alpha ages and enrages for example displays increased adhesion of proinflammatory mononuclear cells at least in part via vcam 1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | that the proinflammatory effects of vcam 1 are not limited to cellular adhesion events as binding of ligand to vcam 1 in endothelial cell lines and primary cultures induced activation of endothelial nadph oxidase a process shown to be essential for lymphocyte migration through the stimulated cells 24 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings suggest that activation of rage at the cell surface may initiate a cascade of events including activation of nadph oxidase and a range of proinflammatory mediators such as vcam 1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | finally it is essential to consider that ligand induced activation of rage results in generation of rois by routes other than nadph oxidase in distinct milieu. |
| 12805 | XDH | xanthine dehydrogenase | xanthine oxidase | 1.0 | for example additional potential sources of rage mediated roi include activation of the mitochondrial respiratory chain microsomal enzymes xanthine oxidase and arachidonic acid pathways 7 47 49 54 . |
| 613 | APOE | apolipoprotein E | apolipoprotein e | 1.0 | consistent with the concept that multiple sources of pathogenic roi exist in the cellular microenvironment it was not surprising that breeding of gp91phox null mice with mice deficient in apolipoprotein e did not inhibit or suppress atherosclerosis 15 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although the present studies support the concept that activated nadph oxidase is a central target of rage and that rois generated by this mechanism may significantly impact on cellular properties a challenge of future work will be to determine the potential contribution of dis |
| 1516 | CAT | catalase | catalase | 1.0 | where indicated drbc were incubated in the presence or absence of the soluble receptor for advanced glycation end products srage; 60 microg/ml superoxide dismutase sod; 300 u/ml catalase 100 u/ml probucol 50 microm or n acetylcysteine nac; 0.03 m . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | where indicated drbc were incubated in the presence or absence of the soluble receptor for advanced glycation end products srage; 60 microg/ml superoxide dismutase sod; 300 u/ml catalase 100 u/ml probucol 50 microm or n acetylcysteine nac; 0.03 m . |
| 1516 | CAT | catalase | catalase | 1.0 | where indicated drbc were incubated in the presence or absence of rat srage 60 microg/ml catalase 100 u/ml sod 300 u/ml probucol 50 microm diphenyliodonium chloride dpi; 5 microm or n monomethyl l arginine l nmma; 0.001 m . |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | incubation of huvec with drbc a or cml modified adducts b enhances cell surface expression of vascular cell adhesion molecule 1 vcam 1 . |
| 3528 | F10 | coagulation factor X | factor xa | 1.0 | procoagulant activity was assessed by an amydolytic assay using a factor xa specific chromogenic substrate as described in text. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase is required for age mediated enhanced tissue factor activity in murine macrophages mps . |
| 3528 | F10 | coagulation factor X | factor xa | 1.0 | procoagulant activity was assessed by an amydolytic assay by use of a factor xa specific chromogenic substrate as described in text. |
| 399 | ALB | albumin | albumin | 1.0 | our previous studies suggested that incubation of huvec with age albumin or ages immunoisolated from the plasma of patients with diabetes resulted in increased transcription and translation of vcam 1 44 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | strongly suggestive of a role for activation of nadph oxidase was the finding that marked suppression of drbc mediated expression of vcam 1 resulted in the presence of dpi fig 2 a . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in addition preincubation of the monolayers with dpi and another inhibitor of nadph oxidase hmap 42 resulted in suppression of the effects of cml ova fig 2 b . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to determine whether the observed effects of ages were due at least in part to activation of nadph oxidase we tested the concept that in murine macrophages lacking a critical component of nadph oxidase gp91 the effects of age would be abrogated. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with an important role for nadph oxidase in mediating the effects of age rage macrophages retrieved from gp91 null mice displayed complete inhibition of age induced tf activity fig 4 . |