)| PMID |
12874435 ( ) |
|---|---|
| Title | ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. |
| Abstract | Oxidative stress has emerged as an important pathogenic factor in the development of long-term complications, such as atherosclerosis and nephropathy, in patients with diabetes. Whereas multiple enzymes and processes can contribute to oxidative stress, recent studies indicate that a multicomponent phagocyte-type NADPH oxidase is a major source of reactive oxygen species (ROS) production in many nonphagocytic cells, including fibroblasts, vascular smooth muscle cells, endothelial cells, renal mesangial cells, and tubular cells. Under physiologic conditions, nonphagocytic NADPH oxidases have very low-level constitutive activity. However, enzyme activity can be upregulated both acutely and chronically in response to stimuli such as growth factors, cytokines, high glucose, and hyperlipidemia. ROS production by the oxidase may serve a signaling role or may lead to oxidative damage. This article reviews current knowledge of the nonphagocyte-NADPH oxidases at both structural and biochemical levels and discusses the possible role of these enzymes in the pathophysiology of diabetic nephropathy. King's College London, London, United Kingdom. jian-mei.li@kcl.ac.uk |
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 |
|---|---|---|---|---|
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 61 | nadph oxidase | |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | 17 | p47 protein | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 14 | angiotensin ii | ang ii | Ang | |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | 11 | rac1 | rac1-induced | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 10 | TNF-alpha. | tnf alpha | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 7 | p40 | MAPK | |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | 6 | cytochrome b | |
| 7891 | NOX4 | NADPH oxidase 4 | 6 | Nox4 | Renox | |
| 7889 | NOX1 | NADPH oxidase 1 | 5 | mitogenic oxidase | Mox-1 | gp91 2 | Nox1 | |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | 5 | p22 | |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | 3 | chronic granulomatous disease | p67 | |
| 3415 | EPO | erythropoietin | 2 | erythropoietin | |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | 2 | rac | |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | 2 | PDGF | PDGF-induced | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | Nox2 | |
| 6081 | INS | insulin | 1 | insulin | |
| 12680 | VEGFA | vascular endothelial growth factor A | 1 | vascular endothelial growth factor | |
| 1516 | CAT | catalase | 1 | catalase | |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | 1 | p21 | |
| 7890 | NOX3 | NADPH oxidase 3 | 1 | Nox3 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | one gp91 subunit and at least four cytosolic subunits (p47 p47 p67 p40 and the small GTPase rac 1 or rac |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p40 | 1.7 | subunit and at least four cytosolic subunits (p47 p47 p67 p40 and the small GTPase rac 1 or rac 2 ( |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | It comprises a membrane-associated cytochrome b 558 composed of one p22 (where where phox stands for phagocyte oxidase and one gp91 |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.2 | gp91 subunit and at least four cytosolic subunits (p47 p47 p67 p40 and the small GTPase rac 1 or rac 2 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | rac | 0.0 | cytosolic subunits (p47 p47 p67 p40 and the small GTPase rac 1 or rac 2 ( 1 |
| 391 | AKT1 | v-akt murine thymoma viral oncogene homolog 1 | rac | 0.0 | p47 p67 p40 and the small GTPase rac 1 or rac 2 ( 1 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | For example both types of oxidase express p22 p47 and rac1 subunits |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | For example both types of oxidase express p22 p47 and rac1 subunits |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.1 | For example both types of oxidase express p22 p47 and rac1 subunits |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | Nox2 | 1.3 | Using this new terminology Nox2 represents the neutrophil gp91 ( Table 1 gp91 is also |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | The first homologue of gp91 namely Nox1 was found to have significant pro-proliferative activity and is also |
| 7889 | NOX1 | NADPH oxidase 1 | Mox-1 | 0.9 | also therefore known by the alternative term mitogenic oxidase or Mox-1 |
| 7889 | NOX1 | NADPH oxidase 1 | Nox1 | 0.9 | Nox1 shares 56% sequence homology with neutrophil gp91 ( 2 12 |
| 7890 | NOX3 | NADPH oxidase 3 | Nox3 | 0.9 | Nox3 is known only from its genomic sequence ( 11 |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 2.4 | A homologue of gp91 termed Nox4 (or or Renox has been cloned in the kidney |
| 7891 | NOX4 | NADPH oxidase 4 | Renox | 1.9 | A homologue of gp91 termed Nox4 (or or Renox has been cloned in the kidney |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 2.4 | The predicted Nox4 protein consists of 578 amino acids with 39% homology to |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 2.4 | Nox4 expression was found to be abundant in human distal tubular |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 2.4 | Nox4 was also found abundantly expressed in fetal kidney an organ |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | it is generally accepted that the majority of the gp91 -p22 heterodimer is located on the plasma membrane whereas other regulatory |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | Upon neutrophil activation the cytosolic components p47 p67 p40 and rac1 translocate to the membrane and associate |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p40 | 1.7 | Upon neutrophil activation the cytosolic components p47 p67 p40 and rac1 translocate to the membrane and associate with the |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | Upon neutrophil activation the cytosolic components p47 p67 p40 and rac1 translocate to the membrane and associate with the cytochrome to |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | p67 | 0.2 | Upon neutrophil activation the cytosolic components p47 p67 p40 and rac1 translocate to the membrane and associate with |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | Several studies have shown a crucial role of the p47 subunit in agonist-induced (angiotensin angiotensin II Ang II PMA TNF-alpha |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | p47 subunit in agonist-induced (angiotensin angiotensin II Ang II PMA TNF-alpha growth factors and thrombin vascular cell NADPH oxidase activation ( |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | endothelial cells isolated from wild-type mice respond to PMA and TNF-alpha with a significant increase in O 2 generation |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | This response was completely lost in cells isolated from p47 knockout mice |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | Transfection of the full-length p47 cDNA into p47 coronary microvascular endothelial cells (CMEC) CMEC caused |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | Transfection of the full-length p47 cDNA into p47 coronary microvascular endothelial cells (CMEC) CMEC caused expression of p47 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | p47 coronary microvascular endothelial cells (CMEC) CMEC caused expression of p47 protein and restoration of the ROS response to PMA and |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 0.5 | protein and restoration of the ROS response to PMA and TNF-alpha. |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | In wild-type CMEC transfection of antisense p47 cDNA substantially reduced p47 expression and caused loss of the |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | In wild-type CMEC transfection of antisense p47 cDNA substantially reduced p47 expression and caused loss of the ROS response to PMA |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha | 0.5 | and caused loss of the ROS response to PMA and TNF-alpha ( 18 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | It is widely known that p47 phosphorylation plays a pivotal role in neutrophil NADPH oxidase activation |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | of activation of NADPH oxidase correspond to the kinetics of p47 phosphorylation ( 25 26 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | It is possible that phosphorylation of p47 may also play a role in agonist-induced upregulation of nonphagocytic |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | that has been well studied in nonphagocytes is the GTPase rac1 which binds to p67 and activates NADPH oxidase in its |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | In endothelial cells dominant-negative rac1 abrogates both basal ( 29 and shear stress-induced NADPH oxidase-dependent |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | threshold level of NADPH oxidase-generated ROS which was regulated by rac1 |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | PDGF-induced | 0.3 | ( 32 reported that PDGF-induced cell cycle activation in airway smooth muscle cells was NADPH |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | oxidase dependent and was inhibited by a dominant-negative allele of rac1 |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | aortic endothelial cells was connected to a feedback loop whereby rac1 protein turnover was accelerated via increased degradation of rac1 by |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | whereby rac1 protein turnover was accelerated via increased degradation of rac1 by the proteasome and was strongly dependent on the redox |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1-induced | 0.0 | ( 33 showed that rac1-induced O 2 production in human aortic endothelial cells was connected |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | as H 2 O 2 promote the degradation of ubiquitinated rac1 whereas inhibitors of NADPH oxidase such as diphenyleneiodonium block the |
| 9801 | RAC1 | ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) | rac1 | 0.5 | NADPH oxidase such as diphenyleneiodonium block the degradation of ubiquitinated rac1 by the proteasome ( 33 |
| 1784 | CDKN1A | cyclin-dependent kinase inhibitor 1A (p21, Cip1) | p21 | 1.4 | sensitive including the transcriptional factor NF-kB the small G protein p21 (Ras), Ras and Src ( 8 36 37 |
| 8799 | PDGFA | platelet-derived growth factor alpha polypeptide | PDGF | 0.3 | transduction in response to several cytokines e.g Ang II thrombin PDGF TNF-alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF-alpha. | 0.5 | in response to several cytokines e.g Ang II thrombin PDGF TNF-alpha. |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | Several members of the mitogen-activated protein kinase (MAPK) MAPK family are redox sensitive |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | Ang II-induced MAPK activation in vascular cells requires NADPH oxidase-derived ROS because Ang |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | NADPH oxidase-derived ROS because Ang II was unable to activate MAPK in aortas from p47 knockout mice ( 23 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | Ang II was unable to activate MAPK in aortas from p47 knockout mice ( 23 |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 0.1 | Ang II-induced MAPK activation in vascular cells requires NADPH oxidase-derived ROS |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 0.1 | MAPK activation in vascular cells requires NADPH oxidase-derived ROS because Ang II was unable to activate MAPK in aortas from p47 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | Similarly in cultured VSMC Ang II-induced MAPK activation could be inhibited by antisense oligonucleotides or an antibody |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | Ang | 0.1 | Similarly in cultured VSMC Ang II-induced MAPK activation could be inhibited by antisense oligonucleotides or |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.0 | could be inhibited by antisense oligonucleotides or an antibody against p22 implicating a role of NADPH oxidase-derived ROS ( 40 |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAPK | 1.7 | found a good correlation between NADPH oxidase-derived ROS production and MAPK activation during the development of cardiac hypertrophy ( 41 |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | The expression of p22 p47 and p67 has been reported in renal mesangial cells ( |
| 7891 | NOX4 | NADPH oxidase 4 | Nox4 | 2.4 | has been reported in renal mesangial cells ( 5 and Nox4 was cloned from the kidney and found highly expressed in |
| 2577 | CYBA | cytochrome b-245, alpha polypeptide | p22 | 0.1 | The expression of p22 p47 and p67 has been reported in renal mesangial cells |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 | 1.1 | in a rat model of diabetic nephropathy upregulation of the p47 subunit of NADPH oxidase and an increase in ROS production |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | whereas multiple enzymes and processes can contribute to oxidative stress recent studies indicate that a multicomponent phagocyte type nadph oxidase is a major source of reactive oxygen species ros production in many nonphagocytic cells including fibroblasts vascular smooth muscle cells endothelial cells renal mesangial cells and tubular cells. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the nadph oxidase was originally discovered in neutrophils where it is a potent source of millimolar quantities of superoxide o 2 during phagocytosis and plays a vital role in nonspecific host defense 1 . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | it comprises a membrane associated cytochrome b 558 composed of one p22 where phox stands for phagocyte oxidase and one gp91 subunit and at least four cytosolic subunits p47 p67 p40 and the small gtpase rac 1 or rac 2 1 . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | is normally dormant in resting neutrophils but is rapidly activated upon appropriate stimulation in a process involving the translocation and association of cytosolic subunits with the membrane bound cytochrome b 558 . |
| 7661 | NCF2 | neutrophil cytosolic factor 2 (65kDa, chronic granulomatous disease, autosomal 2) | chronic granulomatous disease | 1.0 | mutations in essential components of the oxidase lead to the condition of chronic granulomatous disease which is characterized by recurrent life threatening infections. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nphagocytic cells such as fibroblasts; endothelial cells; vascular smooth muscle cells vsmc ; and renal mesangial tubular and other cells also possess o 2 producing enzymes analogous to the phagocyte nadph oxidase 2 7 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the low amounts of ros produced by nonphagocytic nadph oxidase may function as second messengers to influence redox sensitive signal transduction pathways referred to as redox signaling . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | potential role of nonphagocytic nadph oxidase in the pathogenesis of diabetic nephropathy. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | various factors are involved in the activation of nadph oxidase and ros production. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | gp91 is the beta subunit of cytochrome b 558 and is the key catalytic subunit of the nadph oxidase. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | gp91 is the beta subunit of cytochrome b 558 and is the key catalytic subunit of the nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | several homologues of gp91 termed nox for nadph oxidase have recently been reported to be expressed in nonphagocytic cells 11 . |
| 7889 | NOX1 | NADPH oxidase 1 | mitogenic oxidase | 1.0 | the first homologue of gp91 namely nox1 was found to have significant pro proliferative activity and is also therefore known by the alternative term mitogenic oxidase or mox 1. |
| 7889 | NOX1 | NADPH oxidase 1 | gp91 2 | 1.0 | nox1 shares 56% sequence homology with neutrophil gp91 2 12 . |
| 3415 | EPO | erythropoietin | erythropoietin | 1.0 | nox4 expression was found to be abundant in human distal tubular cells and suggested to function as an oxygen sensor for erythropoietin synthesis 6 13 . |
| 3415 | EPO | erythropoietin | erythropoietin | 1.0 | nox4 was also found abundantly expressed in fetal kidney an organ that is not considered to produce highly erythropoietin; it might be involved in the regulation of renal cell growth and death 6 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | subcellular location and assembly of the nonphagocytic nadph oxidase |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | on the basis of the above information it was assumed that in unstimulated nonphagocytic cells the nadph oxidase would also comprise a predominantly plasma membrane bound cytochrome b 558 with the other units present in the cytosol. |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | on the basis of the above information it was assumed that in unstimulated nonphagocytic cells the nadph oxidase would also comprise a predominantly plasma membrane bound cytochrome b 558 with the other units present in the cytosol. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | y using a range of complementary methods including confocal microscopy plasma membrane protein biotinylation subcellular fractionation and co immunoprecipitation we showed that 1 the vast majority of nadph oxidase subunit expression and functional activity in endothelial cells is intracellular rather than plasma membrane bound; 2 a significant proportion of the nadph oxidase subunits in unstimulated cells are |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | subunit expression and functional activity in endothelial cells is intracellular rather than plasma membrane bound; 2 a significant proportion of the nadph oxidase subunits in unstimulated cells are present as fully preassembled and functional ros generating complexes; and 3 the functional oxidase is associated with the intracellular cytoskeleton particularly i |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | because the association of "cytosolic" subunits with cytochrome b 558 is thought to initiate oxidase activity the finding of seemingly preassembled nadph oxidase complexes in endothelial cells is likely to account for the low level ros generating activity observed in unstimulated nonproliferating cells 14 15 . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | because the association of "cytosolic" subunits with cytochrome b 558 is thought to initiate oxidase activity the finding of seemingly preassembled nadph oxidase complexes in endothelial cells is likely to account for the low level ros generating activity observed |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the interaction between the cytoskeleton and oxidase components may play an important role in localizing and stabilizing the nadph oxidase complex. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although the structure of the nadph oxidase in other nonphagocytic cells has not yet been reported it seems likely that it will be similar. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | agonist induced nadph oxidase activation |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | one of the particular attributes of the nonphagocyte nadph oxidase is that the oxidase not only is "constitutively" active but also responds to hormones growth factors cytokines and mechanical stress 2 8 16 20 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | precise mechanisms underlying agonist induced nonphagocyte nadph oxidase activation are not yet understood but it is clear that both acute protein modification and chronic changes in expression levels may be involved. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | several studies have shown a crucial role of the p47 subunit in agonist induced angiotensin ii [ang ii] pma tnf alpha growth factors and thrombin vascular cell nadph oxidase activation 18 21 23 and in the development of atherosclerotic lesions in apoe / mice 24 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | several studies have shown a crucial role of the p47 subunit in agonist induced angiotensin ii [ang ii] pma tnf alpha growth factors and thrombin vascular cell nadph oxidase activation 18 21 23 and in the development of atherosclerotic lesions in apoe / mice 24 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | several studies have shown a crucial role of the p47 subunit in agonist induced angiotensin ii [ang ii] pma tnf alpha growth factors and thrombin vascular cell nadph oxidase activation 18 21 23 and in the development of atherosclerotic lesions in apoe / mice 24 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | several studies have shown a crucial role of the p47 subunit in agonist induced angiotensin ii [ang ii] pma tnf alpha growth factors and thrombin vascular cell nadph oxidase activation 18 21 23 and in the development of atherosclerotic lesions in apoe / mice 24 . |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | we also found that coronary microvascular endothelial cells isolated from wild type mice respond to pma and tnf alpha with a significant increase in o 2 generation. |
| 7660 | NCF1 | neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1) | p47 protein | 1.0 | transfection of the full length p47 cdna into p47 coronary microvascular endothelial cells cmec caused expression of p47 protein and restoration of the ros response to pma and tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | transfection of the full length p47 cdna into p47 coronary microvascular endothelial cells cmec caused expression of p47 protein and restoration of the ros response to pma and tnf alpha. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | in wild type cmec transfection of antisense p47 cdna substantially reduced p47 expression and caused loss of the ros response to pma and tnf alpha 18 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it is widely known that p47 phosphorylation plays a pivotal role in neutrophil nadph oxidase activation by providing physical binding domains to cytochrome b 558 and p67 25 . |
| 7427 | MT-CYB | mitochondrially encoded cytochrome b | cytochrome b | 1.0 | it is widely known that p47 phosphorylation plays a pivotal role in neutrophil nadph oxidase activation by providing physical binding domains to cytochrome b 558 and p67 25 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the kinetics of activation of nadph oxidase correspond to the kinetics of p47 phosphorylation 25 26 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | another regulatory subunit that has been well studied in nonphagocytes is the gtpase rac1 which binds to p67 and activates nadph oxidase in its gtp bound state 27 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | microinjection of constitutively active h rac1 into hepg2 cells increases nadph oxidase dependent ros generation whereas microinjection of dominant negative mutant h rac1 inhibits nadph oxidase 28 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in endothelial cells dominant negative rac1 abrogates both basal 29 and shear stress induced nadph oxidase dependent ros production 30 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 31 found that human endothelial cell responses to vascular endothelial growth factor required a threshold level of nadph oxidase generated ros which was regulated by rac1. |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | 31 found that human endothelial cell responses to vascular endothelial growth factor required a threshold level of nadph oxidase generated ros which was regulated by rac1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 32 reported that pdgf induced cell cycle activation in airway smooth muscle cells was nadph oxidase dependent and was inhibited by a dominant negative allele of rac1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | redox regulation of nadph oxidase: feedback and feedforward mechanisms |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | another feature of nonphagocyte nadph oxidase from the literature is that enzyme activity may be regulated by its own product ros. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ros such as h 2 o 2 promote the degradation of ubiquitinated rac1 whereas inhibitors of nadph oxidase such as diphenyleneiodonium block the degradation of ubiquitinated rac1 by the proteasome 33 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 34 showed a feedforward mechanism such that exogenous exposure of smc or fibroblasts to h 2 o 2 activated nadph oxidase to produce endogenous o 2 thereby amplifying the vascular injury process. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the hypothesis is that the self limiting mechanism may be involved mainly in the maintenance of the low output of the nonphagocyte nadph oxidase during physiologic conditions whereas the feedforward mechanism may play a role in nadph oxidase dependent oxidative stress in a variety of diseases including atherosclerosis and inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | during physiologic conditions whereas the feedforward mechanism may play a role in nadph oxidase dependent oxidative stress in a variety of diseases including atherosclerosis and inflammation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the amount of ros produced by nonphagocyte nadph oxidase is normally relatively low even in many pathologic settings and is mainly generated in the intracellular compartment. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tnf alpha | 1.0 | it has been clearly demonstrated that ros generated by nadph oxidase are involved in signal transduction in response to several cytokines e.g. ang ii thrombin pdgf tnf alpha. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | it has been clearly demonstrated that ros generated by nadph oxidase are involved in signal transduction in response to several cytokines e.g. ang ii thrombin pdgf tnf alpha. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it has been clearly demonstrated that ros generated by nadph oxidase are involved in signal transduction in response to several cytokines e.g. ang ii thrombin pdgf tnf alpha. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | agonist binding to receptor rapidly activates nadph oxidase followed by elevated intracellular o 2 and h 2 o 2 levels and activation of signaling molecules including protein tyrosine kinases serine/threonine kinases phospholipases and ca dependent pathways. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in vsmc ang ii dependent rises in intracellular ca can be blocked by inhibitors of nadph oxidase or genetic manipulation of nadph oxidase expression 2 8 29 38 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in vsmc ang ii dependent rises in intracellular ca can be blocked by inhibitors of nadph oxidase or genetic manipulation of nadph oxidase expression 2 8 29 38 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in blood vessels ang ii infusion results in an increased expression and activity of nadph oxidase which is partly pkc dependent 39 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in blood vessels ang ii infusion results in an increased expression and activity of nadph oxidase which is partly pkc dependent 39 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in the heart ang ii increases o 2 production and cardiac hypertrophy only in wild type animals but not in gp91 knockout mice suggesting a role for nadph oxidase 36 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the heart ang ii increases o 2 production and cardiac hypertrophy only in wild type animals but not in gp91 knockout mice suggesting a role for nadph oxidase 36 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii induced mapk activation in vascular cells requires nadph oxidase derived ros because ang ii was unable to activate mapk in aortas from p47 knockout mice 23 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ang ii induced mapk activation in vascular cells requires nadph oxidase derived ros because ang ii was unable to activate mapk in aortas from p47 knockout mice 23 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | similarly in cultured vsmc ang ii induced mapk activation could be inhibited by antisense oligonucleotides or an antibody against p22 implicating a role of nadph oxidase derived ros 40 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | similarly in cultured vsmc ang ii induced mapk activation could be inhibited by antisense oligonucleotides or an antibody against p22 implicating a role of nadph oxidase derived ros 40 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in the heart we also found a good correlation between nadph oxidase derived ros production and mapk activation during the development of cardiac hypertrophy 41 . |
| 1516 | CAT | catalase | catalase | 1.0 | ess antioxidant defense systems that include ros degrading molecules ros scavengers such as uric acid ascorbic acid and sulfhydryl containing molecules e.g glutathione and antioxidant enzymes such as catalase glutathione peroxidase and superoxide dismutases. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | 3 nadph oxidase was regarded as the most important source of o 2 in the vessel wall of experimental hypertension models including ang ii induced hypertension renovascular hypertension and genetic hypertension. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 3 nadph oxidase was regarded as the most important source of o 2 in the vessel wall of experimental hypertension models including ang ii induced hypertension renovascular hypertension and genetic hypertension. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 42 reported that vessels from patients with coronary heart disease and with identified risk factors had much higher nadph oxidase activity than vessels from control groups; they also found that diabetes and hypercholesterolemia were independently associated with increased nadph oxidase derived ros generation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | activity than vessels from control groups; they also found that diabetes and hypercholesterolemia were independently associated with increased nadph oxidase derived ros generation. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in an animal model of pressure overload cardiac hypertrophy and failure enhanced nadph oxidase activity coexisted with cardiac dysfunction 41 43 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | impaired endothelium dependent cardiac function as a result of increased nadph oxidase dependent ros generation could be restored by treatment with the antioxidant vitamin c or deferoxamine 43 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | targeted inhibition of nadph oxidase protected the liver from ischemia reperfusion injury figure 1 44 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although the role of nadph oxidase in type 1 diabetes is still not clear ros have been found to be among the first damaging species generated in islet cells after streptozotocin administration in rodents and may kill islet cells 45 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | 46 showed that incubation of human endothelial cells with red blood cells isolated from patients with type 1 diabetes but not from normal volunteers activated endothelial nadph oxidase and increased endothelial ros generation which was due to the formation of advanced glycation end products on the surface of diabetic red blood cells. |
| 6081 | INS | insulin | insulin | 1.0 | in type 2 diabetes a major pathophysiological alteration is insulin resistance and there is a growing body of evidence demonstrating the coexistence of insulin resistance and endothelial dysfunction. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | endothelial dysfunction characterized by increased nadph oxidase dependent ros generation has been shown in animal models of diabetes 47 48 and in patients with diabetes 42 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | although the origin of increased ros generation in renal diseases is multifactorial the kidney is now known to express nadph oxidase and generate ros 6 10 13 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | it has been shown that kidneys from adult spontaneously hypertensive rats shr express significantly higher level of nadph oxidase and produce more ros than normal controls 49 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in another study the enzymatic sources of o 2 generation were examined in different regions of the rat kidney and it was reported that a higher nadph oxidase dependent o 2 generation was present in renal cortex and outer medulla than in the papilla 50 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | glomerular mesangial cells are target cells of diabetic nephropathy and endowed with a nadph oxidase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | the endothelial cell lining of the glomerulus is strategically situated at the interface between the blood and the mesangium and expresses a constitutively active nadph oxidase 49 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | exposing mesangial cells as well as endothelial cells to a diabetic environment such as high glucose or free fatty acids activates nadph oxidase and increases ros generation 20 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | increased levels of oxidized ldl and hyperlipidemia are also potent activators of nadph oxidase and also recognized as pathogenic factors in long term complications of diabetes 52 53 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | in addition the intrarenal concentration of ang ii is much higher than in the serum. |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | ang ii | 1.0 | ang ii activates nadph oxidase in both mesangial cells 17 and endothelial cells 39 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | ang ii activates nadph oxidase in both mesangial cells 17 and endothelial cells 39 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | more direct in a rat model of diabetic nephropathy upregulation of the p47 subunit of nadph oxidase and an increase in ros production has been demonstrated 54 . |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | in summary the nonphagocytic nadph oxidase has emerged as a potentially important target to focus on to explore the mechanisms underlying the pathogenesis of long term complications in patients with diabetes. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | possible therapeutic approaches include the use of antioxidants or direct pharmaceutical or genetic manipulation of nadph oxidase expression and activity. |