)| PMID |
18378574 ( ) |
|---|---|
| Title | Role of NADPH oxidase in retinal vascular inflammation. |
| Abstract | PURPOSE: In another study, it was demonstrated that NADPH oxidase-derived reactive oxygen species (ROS) are important for ischemia-induced increases in vascular endothelial growth factor (VEGF) and retinal neovascularization. Diabetes-induced increases in retinal ROS, VEGF expression, and vascular permeability are accompanied by increases in the NADPH oxidase catalytic subunit NOX2 within the retinal vessels. The goal of this study was to evaluate the potential role of NOX2 and NADPH oxidase activity in the development of retinal vascular inflammation. METHODS: Studies were performed in wild-type mice, mice lacking NOX2, and mice treated with the NADPH oxidase inhibitor apocynin in models of endotoxemia and streptozotocin-induced diabetes. Intracellular adhesion molecule (ICAM)-1 expression was determined by Western blot analysis. Leukocyte adhesion was assessed by labeling adherent leukocytes with concanavalin A. Vascular permeability was assessed by extravasation of FITC-conjugated albumin. ROS production was determined by dichlorofluorescein imaging. RESULTS: Both endotoxemia- and diabetes-induced increases in ICAM-1 expression and leukostasis were significantly inhibited by deletion of NOX2, indicating that this enzyme is critically involved in both conditions. Moreover, apocynin treatment and deletion of NOX2 were equally effective in preventing diabetes-induced increases in ICAM-1, leukostasis, and breakdown of the blood-retinal barrier, suggesting that NOX2 is primarily responsible for these early signs of diabetic retinopathy. CONCLUSIONS: These data suggest that NOX2 activity has a primary role in retinal vascular inflammation during acute and chronic conditions associated with retinal vascular inflammatory reactions. Targeting this enzyme could be a novel therapeutic strategy for treatment of the retinopathies associated with vascular inflammation. Augusta, Georgia 30912, USA. malshabrawey@mcg.edu |
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 |
|---|---|---|---|---|
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 56 | NOX2-Deficient | NOX2-deficient | NOX2-containing | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 35 | nadph oxidase | |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | 21 | ICAM-1 | |
| 12680 | VEGFA | vascular endothelial growth factor A | 6 | VEGF | vascular endothelial growth factor | |
| 9666 | PTPRC | protein tyrosine phosphatase, receptor type, C | 3 | CD45 | |
| 7891 | NOX4 | NADPH oxidase 4 | 3 | NOX4 | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 2 | mcp 1 | MCP-1 | |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | 2 | ap 1 | AP-1 | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 2 | TNF-alpha | tnf alpha | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 2 | IL-6 | il 6 | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 2 | angiotensin ii | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 1 | p67 | |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | 1 | VCAM-1 | |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | 1 | cytochrome b | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 1 | Rac | |
| 399 | ALB | albumin | 1 | serum albumin | |
| 9393 | PRKCA | protein kinase C, alpha | 1 | protein kinase c | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 1 | NF-kappaB | |
| 1516 | CAT | catalase | 1 | catalase | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 1 | p47 | |
| 7889 | NOX1 | NADPH oxidase 1 | 1 | NOX1 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 1 | p22 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | important for ischemia-induced increases in vascular endothelial growth factor (VEGF) VEGF and retinal neovascularization |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | Diabetes-induced increases in retinal ROS VEGF expression and vascular permeability are accompanied by increases in the |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | are accompanied by increases in the NADPH oxidase catalytic subunit NOX2 within the retinal vessels |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | of this study was to evaluate the potential role of NOX2 and NADPH oxidase activity in the development of retinal vascular |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Studies were performed in wild-type mice mice lacking NOX2 and mice treated with the NADPH oxidase inhibitor apocynin in |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Both endotoxemia- and diabetes-induced increases in ICAM-1 expression and leukostasis were significantly inhibited by deletion of NOX2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | ICAM-1 expression and leukostasis were significantly inhibited by deletion of NOX2 indicating that this enzyme is critically involved in both conditions |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Moreover apocynin treatment and deletion of NOX2 were equally effective in preventing diabetes-induced increases in ICAM-1 leukostasis |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | of NOX2 were equally effective in preventing diabetes-induced increases in ICAM-1 leukostasis and breakdown of the blood-retinal barrier suggesting that NOX2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | ICAM-1 leukostasis and breakdown of the blood-retinal barrier suggesting that NOX2 is primarily responsible for these early signs of diabetic retinopathy |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | These data suggest that NOX2 activity has a primary role in retinal vascular inflammation during |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | AP-1 | 1.0 | Furthermore ROS activate the transcription factors NF-kappaB and AP-1 which play a central and crucial role in inducing the |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | crucial role in inducing the expression of inflammatory cytokines and ICAM-1 |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.0 | Furthermore ROS activate the transcription factors NF-kappaB and AP-1 which play a central and crucial role in |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | Previous work has shown that diabetes-induced increases in VEGF expression leukocyte adhesion and breakdown of the blood-retinal barrier (BRB) |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | cytochrome b 558 which is composed of the catalytic subunit NOX2 (formerly formerly known as gp91 p22 the cytoplasmic subunits p47 |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.3 | of the catalytic subunit NOX2 (formerly formerly known as gp91 p22 the cytoplasmic subunits p47 and p67 and the small Rho |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 0.6 | NOX2 (formerly formerly known as gp91 p22 the cytoplasmic subunits p47 and p67 and the small Rho GTPase Rac |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.3 | formerly known as gp91 p22 the cytoplasmic subunits p47 and p67 and the small Rho GTPase Rac |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | Rac | 0.0 | cytoplasmic subunits p47 and p67 and the small Rho GTPase Rac |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | endothelial cells express the same subunits as well as two NOX2 homologues NOX1 and NOX4 (for for review see Ref |
| 7889 | NOX1 | NADPH oxidase 1 | NOX1 | 0.9 | express the same subunits as well as two NOX2 homologues NOX1 and NOX4 (for for review see Ref |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | express the same subunits as well as two NOX2 homologues NOX1 and NOX4 (for for review see Ref |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | same subunits as well as two NOX2 homologues NOX1 and NOX4 (for for review see Ref |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | studies in animal and tissue culture models have shown that NOX2 is expressed at low levels in normal retinas and in |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | have found that inhibiting NADPH oxidase blocks the upregulation of VEGF expression during diabetic and ischemic retinopathy and prevents vitreoretinal neovascularization |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | was to determine the specific role of NADPH oxidase and NOX2 in retinal vascular inflammation related to acute and chronic vascular |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-deficient | 1.3 | Experiments were performed with C57Bl/6J C57Bl 6J mice and age-matched NOX2-deficient mice backcrossed on a C57Bl/6 C57Bl 6 background (Jackson Jackson |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-deficient | 1.3 | Genotyping of NOX2-deficient mice was performed before the experiment |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Mice lacking NOX2 and age-matched wild-type mice (25 25 g were injected with |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | hours later and prepared for quantification of leukocyte adhesion and ICAM-1 expression in the retina |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Additional groups of age-matched wild-type and NOX2 mice (25 25 g were made diabetic by intraperitoneal injections |
| 9666 | PTPRC | protein tyrosine phosphatase, receptor type, C | CD45 | 1.3 | CD45 immunohistochemistry was performed with a specific anti-CD45 antibody (BD-PharMingen, BD-PharMingen |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | For analysis of ICAM-1 pooled retinas were homogenized in a modified RIPA buffer (20 |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Abrogation of LPS-Induced Increases in Leukocyte Adhesion and ICAM-1 Expression in the Retinas of NOX2-Deficient Mice |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-Deficient | 1.3 | in Leukocyte Adhesion and ICAM-1 Expression in the Retinas of NOX2-Deficient Mice |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-containing | 1.3 | To evaluate whether activity of NOX2-containing NADPH oxidase plays a role in retinal vascular inflammation we |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-deficient | 1.3 | leukocyte adhesion in the retinal vessels of LPS-treated wild-type and NOX2-deficient mice |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | LPS-injected mice was reduced by ~60% in the mice lacking NOX2 compared with wild-type (mean mean _amp_#177 SE = 53 _amp_#177 |
| 9666 | PTPRC | protein tyrosine phosphatase, receptor type, C | CD45 | 1.3 | Immunoreactivity for CD45 confirmed that the adherent cells were leukocytes (Fig Fig 1B |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Because ICAM-1 is a key mediator of leukocyte adhesion we tested whether |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | key mediator of leukocyte adhesion we tested whether deletion of NOX2 affects its expression in the retina |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | blot analyses showed a significant increase in retinal expression of ICAM-1 after the LPS treatment |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | However this increase was significantly reduced in mice lacking NOX2 (Fig Fig 2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | These experiments showed that knocking out NOX2 or inhibiting NADPH oxidase activity by apocynin treatment completely blocks |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | activity by apocynin treatment completely blocks diabetes-induced increases in retinal ICAM-1 levels and leukocyte adhesion and preserves the BRB |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Furthermore the NOX2 deletion and apocynin treatment also substantially reduced ROS formation implying |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | during LPS-induced endotoxemia we also determined the effect of deleting NOX2 on ICAM-1 expression and leukostasis in LPS-injected mice |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | endotoxemia we also determined the effect of deleting NOX2 on ICAM-1 expression and leukostasis in LPS-injected mice |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | treatment and that this effect is abrogated in mice lacking NOX2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | These findings confirm the importance of the activity of NOX2 NADPH oxidase in mediating retinal vascular inflammatory reactions in both |
| 12680 | VEGFA | vascular endothelial growth factor A | VEGF | 2.8 | studies showing that diabetes-induced increases in oxidative stress expression of VEGF and ICAM-1 leukostasis and breakdown of the BRB are all |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | that diabetes-induced increases in oxidative stress expression of VEGF and ICAM-1 leukostasis and breakdown of the BRB are all blocked by |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | oxidase activation blocks leukocyte adhesion to the retinal vessels and ICAM-1 expression in models of uveitis or diabetes |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.0 | oxidase activity are accompanied by upregulation of inflammatory cytokines (IL-6 IL-6 and TNF-alpha chemokines (MCP-1), MCP-1 and vascular cell adhesive molecules |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | are accompanied by upregulation of inflammatory cytokines (IL-6 IL-6 and TNF-alpha chemokines (MCP-1), MCP-1 and vascular cell adhesive molecules (VCAM-1), VCAM-1 |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 1.0 | upregulation of inflammatory cytokines (IL-6 IL-6 and TNF-alpha chemokines (MCP-1), MCP-1 and vascular cell adhesive molecules (VCAM-1), VCAM-1 providing further support |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.2 | TNF-alpha chemokines (MCP-1), MCP-1 and vascular cell adhesive molecules (VCAM-1), VCAM-1 providing further support for the role of NADPH oxidase in |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | knowledge the present study is the first to show that NOX2 is critically involved in retinal vascular inflammation and diabetes-induced breakdown |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | our finding that diabetes-induced ROS formation is reduced in the NOX2 knockout mouse retina others have reported that deletion of NOX2 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | NOX2 knockout mouse retina others have reported that deletion of NOX2 inhibits ROS production in various tissues including aorta in DOCA |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Furthermore knocking out NOX2 has been shown to reduce leukocyte adhesion in a mouse |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | However our finding that increases in retinal expression of ICAM-1 and leukocyte adhesion to endothelial cells were substantially inhibited in |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | model and completely blocked in mice with diabetes that lacked NOX2 or in diabetic mice treated with apocynin provides strong evidence |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | apocynin provides strong evidence of the critical role played by NOX2 and NADPH oxidase activity in mediating retinal vascular inflammatory reactions |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | NOX2 is expressed by both phagocytic and vascular endothelial cells |
| 7891 | NOX4 | NADPH oxidase 4 | NOX4 | 0.9 | endothelial cells ROS are produced mainly by activity of the NOX4 enzyme |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | shown that diabetes and high-glucose treatment promote significant increases in NOX2 levels in retinal endothelial cells |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | present results suggest that reactive oxygen species produced by the NOX2 NADPH oxidase mediate retinal vascular inflammatory reactions associated with both |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Wild-type mice and mice lacking NOX2 were injected with LPS (0.1 0.1 mg/kg, mg kg intraperitoneal |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | of LPS-injected wild-type mice (+/+) compared with the mice lacking NOX2 (-/-) - - * P _lt_ 0.05 vs WT ( |
| 9666 | PTPRC | protein tyrosine phosphatase, receptor type, C | CD45 | 1.3 | ( B Immunolabeling with Con A and an antibody against CD45 confirms that the adherent cells were leukocytes |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Western blot analysis of ICAM-1 in LPS-injected mice |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | ICAM-1 is increased in LPS-injected wild-type mice (+/+) compared with the |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | The effect was significantly inhibited in mice lacking NOX2 (LPS LPS * P _lt_ 0.05 vs control # P |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | mice (C) C and decreased leukocytes in diabetic mice lacking NOX2 (DM DM or treated with apocynin (DM+apocynin) DM apocynin * |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Western blot analysis of ICAM-1 in diabetic mice |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | ICAM-1 was increased in diabetic wild-type mice (DM DM compared with |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | This effect was prevented in diabetic mice lacking NOX2 (D D or treated with apocynin (DM+apocynin) DM apocynin * |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | The increase was blocked in NOX2 diabetic mice (D D and in diabetic mice treated with |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | (DM DM compared with the control wild-type (C) C or NOX2 knockout (C C mice |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | diabetic mice with apocynin (DM-apocynin) DM-apocynin or by deletion of NOX2 (DM DM * P _lt_ 0.05 vs C # P |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Blockade of Diabetes-Induced Increases in Leukocyte Adhesion and ICAM-1 Expression by Deletion of NOX2 or Inhibition of NADPH Oxidase |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Increases in Leukocyte Adhesion and ICAM-1 Expression by Deletion of NOX2 or Inhibition of NADPH Oxidase |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | To test whether NOX2 expression and NADPH oxidase activity have a role in vascular |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | diabetic retinopathy we examined leukocyte-endothelial cell attachment and expression of ICAM-1 in the retinas of diabetic mice lacking NOX2 or treated |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | expression of ICAM-1 in the retinas of diabetic mice lacking NOX2 or treated with apocynin |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | This increase was substantially reduced by deletion of NOX2 or apocynin treatment (Fig Fig 3 |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Western blot analysis showed a significant increase in expression of ICAM-1 in the diabetic retina which also was completely blocked by |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | which also was completely blocked by apocynin or deletion of NOX2 (Fig Fig 4 |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-containing | 1.3 | These results indicate that activity of NOX2-containing NADPH oxidase is critically involved in leukocyte-endothelial cell attachment in |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Effect of Deletion of NOX2 on ROS Formation in the Diabetic Retina |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Deletion of NOX2 or treatment of the mice with apocynin prevented the diabetes-induced |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | in ROS formation (Fig Fig 5 indicating the role of NOX2 and NADPH oxidase activity in diabetes-induced increases in oxidative stress |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | Effect of Deletion of NOX2 on the BRB in Diabetic Mice |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | ICAM-1 | 1.5 | Because increases in ICAM-1 expression and leukocyte adhesion have been shown to correlate with |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | of BRB in diabetes we also determined the effects of NOX2 deletion and apocynin treatment on retinal vascular permeability |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2 | 1.3 | an assay for extravasation of BSA-Alexa-Fluor 488 conjugate showed that NOX2 deletion or apocynin treatment prevented diabetes-induced increases in retinal vascular |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | NOX2-containing | 1.3 | retinal vascular permeability (Fig Fig 6 indicating that activity of NOX2-containing NADPH oxidase also plays a role in mediating the vascular |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in another study it was demonstrated that nadph oxidase derived reactive oxygen species ros are important for ischemia induced increases in vascular endothelial growth factor vegf and retinal neovascularization. |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | in another study it was demonstrated that nadph oxidase derived reactive oxygen species ros are important for ischemia induced increases in vascular endothelial growth factor vegf and retinal neovascularization. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | diabetes induced increases in retinal ros vegf expression and vascular permeability are accompanied by increases in the nadph oxidase catalytic subunit nox2 within the retinal vessels. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the goal of this study was to evaluate the potential role of nox2 and nadph oxidase activity in the development of retinal vascular inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies were performed in wild type mice mice lacking nox2 and mice treated with the nadph oxidase inhibitor apocynin in models of endotoxemia and streptozotocin induced diabetes. |
| 3796 | FOS | v-fos FBJ murine osteosarcoma viral oncogene homolog | ap 1 | 1.0 | furthermore ros activate the transcription factors nf kappab and ap 1 which play a central and crucial role in inducing the expression of inflammatory cytokines and icam 1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | however studies in models of atherosclerosis and other forms of peripheral vascular disease have implicated nadph oxidase in the inflammatory reaction. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in phagocytic cells nadph oxidase is a multiprotein complex consisting of membrane bound cytochrome b 558 which is composed of the catalytic subunit nox2 formerly known as gp91 p22 the cytoplasmic subunits p47 and p67 and the small r |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | in phagocytic cells nadph oxidase is a multiprotein complex consisting of membrane bound cytochrome b 558 which is composed of the catalytic subunit nox2 formerly known as gp91 p22 the cytoplasmic subunits p47 and p67 and the small rho gtpase rac. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | moreover we have found that inhibiting nadph oxidase blocks the upregulation of vegf expression during diabetic and ischemic retinopathy and prevents vitreoretinal neovascularization during ischemic retinopathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the goal of the present study was to determine the specific role of nadph oxidase and nox2 in retinal vascular inflammation related to acute and chronic vascular inflammatory reactions in endotoxemia and diabetic retinopathy respectively. |
| 399 | ALB | albumin | serum albumin | 1.0 | both diabetic and control mice received external jugular vein injections of 10 mg/kg bovine serum albumin bsa alexa fluor 488 conjugate invitrogen molecular probes eugene or . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | measurement of nadph oxidase activity |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activity of nadph oxidase was assayed using dichlorofluorescein imaging of retinal frozen sections. |
| 1516 | CAT | catalase | catalase | 1.0 | the specificity of the reaction was determined by incubating the retinal sections in buffer containing dhdcf with or without peg sod catalase or apocynin sigma aldrich . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to evaluate whether activity of nox2 containing nadph oxidase plays a role in retinal vascular inflammation we analyzed leukocyte adhesion in the retinal vessels of lps treated wild type and nox2 deficient mice. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these experiments showed that knocking out nox2 or inhibiting nadph oxidase activity by apocynin treatment completely blocks diabetes induced increases in retinal icam 1 levels and leukocyte adhesion and preserves the brb. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | furthermore the nox2 deletion and apocynin treatment also substantially reduced ros formation implying a causal role of nadph oxidase derived ros in the inflammatory reaction. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these findings confirm the importance of the activity of nox2 nadph oxidase in mediating retinal vascular inflammatory reactions in both acute and chronic disease conditions. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a potential link between nadph oxidase activity and vascular inflammatory reactions has been suggested by previous studies showing that diabetes induced increases in oxidative stress expression of vegf and icam 1 leukostasis and breakdown |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | revious studies showing that diabetes induced increases in oxidative stress expression of vegf and icam 1 leukostasis and breakdown of the brb are all blocked by simvastatin which is known to inhibit nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies showing that diabetes induced increases in systemic oxidative stress are blocked by apocynin also support the role of nadph oxidase in diabetic tissue damage. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies showing that retinal leukostasis induced by diabetes or intravitreous injection of angiotensin ii is prevented by treatment with apocynin also support a role for nadph oxidase activity in retinopathy. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | studies showing that retinal leukostasis induced by diabetes or intravitreous injection of angiotensin ii is prevented by treatment with apocynin also support a role for nadph oxidase activity in retinopathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | further support for the role of nadph oxidase in retinal vascular inflammatory reactions comes from studies showing that blockade of angiotensin ii type 1 receptor signaling a known stimulus for nadph oxidase activation blocks leukocyte adhesion to the retinal vessels and icam 1 expression in models of uveitis or diabetes. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | further support for the role of nadph oxidase in retinal vascular inflammatory reactions comes from studies showing that blockade of angiotensin ii type 1 receptor signaling a known stimulus for nadph oxidase activation blocks leukocyte adhesion to the retinal vessels and icam 1 expression in models of uveitis or diabetes. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | es of coronary arteries from diabetic pigs have shown that diabetes induced increases in nadph oxidase activity are accompanied by upregulation of inflammatory cytokines il 6 and tnf alpha chemokines mcp 1 and vascular cell adhesive molecules vcam 1 providing further support for the role of nadph oxidase in vascular inflammation. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | studies of coronary arteries from diabetic pigs have shown that diabetes induced increases in nadph oxidase activity are accompanied by upregulation of inflammatory cytokines il 6 and tnf alpha chemokines mcp 1 and vascular cell adhesive molecules vcam 1 providing further support for the role of nadph oxidase in vascular inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | studies of coronary arteries from diabetic pigs have shown that diabetes induced increases in nadph oxidase activity are accompanied by upregulation of inflammatory cytokines il 6 and tnf alpha chemokines mcp 1 and vascular cell adhesive molecules vcam 1 providing further support for the role of nadph oxid |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activity are accompanied by upregulation of inflammatory cytokines il 6 and tnf alpha chemokines mcp 1 and vascular cell adhesive molecules vcam 1 providing further support for the role of nadph oxidase in vascular inflammation. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | studies of coronary arteries from diabetic pigs have shown that diabetes induced increases in nadph oxidase activity are accompanied by upregulation of inflammatory cytokines il 6 and tnf alpha chemokines mcp 1 and vascular cell adhesive molecules vcam 1 providing further support for the role of nadph oxidase in vascular inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | overall these reports suggest that nadph oxidase derived ros are critically involved in triggering leukocyte endothelial cell adhesion and vascular injury during diabetes or other inflammatory conditions. |
| 9393 | PRKCA | protein kinase C, alpha | protein kinase c | 1.0 | mitochondria derived ros trigger the activation of multiple pathways of hyperglycemic damage including nadph oxidase via protein kinase c. moreover studies in other models indicate that although mitochondrial derived ros are important for the initiation of oxidative stress responses activity of nadph oxidase is needed to sustain suffic |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | mitochondria derived ros trigger the activation of multiple pathways of hyperglycemic damage including nadph oxidase via protein kinase c. moreover studies in other models indicate that although mitochondrial derived ros are important for the initiation of oxidative stress responses activity of nadph oxidase is nee |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | via protein kinase c. moreover studies in other models indicate that although mitochondrial derived ros are important for the initiation of oxidative stress responses activity of nadph oxidase is needed to sustain sufficient levels of ros formation for the transduction of specific cellular responses. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | further study is needed to determine the potential role of mitochondrial ros in activating nadph oxidase in models of diabetes and endotoxemia. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | lly inhibited in the lps model and completely blocked in mice with diabetes that lacked nox2 or in diabetic mice treated with apocynin provides strong evidence of the critical role played by nox2 and nadph oxidase activity in mediating retinal vascular inflammatory reactions in both models. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | further work is also needed to identify the specific cellular source s of the nadph oxidase activity responsible for the retinal vascular inflammatory reactions observed in our experiments. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | during conditions of inflammation or host defense reactions ros are produced at high levels by phagocyte nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in summary our present results suggest that reactive oxygen species produced by the nox2 nadph oxidase mediate retinal vascular inflammatory reactions associated with both acute and chronic models of retinal vascular disease. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | blockade of diabetes induced increases in leukocyte adhesion and icam 1 expression by deletion of nox2 or inhibition of nadph oxidase |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to test whether nox2 expression and nadph oxidase activity have a role in vascular inflammatory processes associated with diabetic retinopathy we examined leukocyte endothelial cell attachment and expression of icam 1 in the retinas of diabetic mice |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | these results indicate that activity of nox2 containing nadph oxidase is critically involved in leukocyte endothelial cell attachment in the diabetic retina. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | to assess the potential contribution of nadph oxidase activity to oxidative stress in the diabetic retina we studied ros generation by using real time dcf imaging of flash frozen retinas. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | deletion of nox2 or treatment of the mice with apocynin prevented the diabetes induced increases in ros formation fig 5 indicating the role of nox2 and nadph oxidase activity in diabetes induced increases in oxidative stress in the retina. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | f bsa alexa fluor 488 conjugate showed that nox2 deletion or apocynin treatment prevented diabetes induced increases in retinal vascular permeability fig 6 indicating that activity of nox2 containing nadph oxidase also plays a role in mediating the vascular permeability increase in diabetes. |