)| PMID |
15297385 ( ) |
|---|---|
| Title | Protein glycation: a firm link to endothelial cell dysfunction. |
| Abstract | The advanced glycation end products (AGEs) are a heterogeneous class of molecules, including the following main subgroups: bis(lysyl)imidazolium cross-links, hydroimidazolones, 3-deoxyglucosone derivatives, and monolysyl adducts. AGEs are increased in diabetes, renal failure, and aging. Microvascular lesions correlate with the accumulation of AGEs, as demonstrated in diabetic retinopathy or renal glomerulosclerosis. On endothelial cells, ligation of receptor for AGE (RAGE) by AGEs induces the expression of cell adhesion molecules, tissue factor, cytokines such as interleukin-6, and monocyte chemoattractant protein-1. A chief means by which AGEs via RAGE exert their effects is by generation of reactive oxygen species, at least in part via stimulation of NADPH oxidase. Diabetes-associated vascular dysfunction in vivo can be prevented by blockade of RAGE. Thus, agents that limit AGE formation, increase the catabolism of these species, or antagonize their binding to RAGE may provide new targets for vascular protection in diabetes. Transfusion Sanguine, Paris, France. |
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 |
|---|---|---|---|---|
| 2197 | COL1A1 | collagen, type I, alpha 1 | 5 | collagen | collagen-induced | |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | 4 | monocyte chemoattractant protein 1 | monocyte chemotactic protein 1 | mcp 1 | MCP-1 | |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | 4 | fibroblast growth factor 2 | FGF2 | |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | 4 | IL-6 | il 6 | interleukin 6 | |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | 4 | nadph oxidase | |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | 3 | vascular cell adhesion molecule 1 | VCAM-1 | |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | 3 | p38 | MAP | |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | 3 | fgf2 | bFGF | |
| 4827 | HBB | hemoglobin, beta | 3 | hemoglobin | |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | 2 | pai 1 | PAI-1 | |
| 4323 | GLO1 | glyoxalase I | 2 | glyoxalase i | |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | 2 | NF-kappaB | |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 2 | SOD | superoxide dismutase | |
| 21420 | CCRK | cell cycle related kinase | 1 | p42 | |
| 2345 | CREB1 | cAMP responsive element binding protein 1 | 1 | CREB | |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | 1 | gp91 phox | |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | 1 | intercellular adhesion molecule 1 | |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | 1 | JNK | |
| 399 | ALB | albumin | 1 | albumin | |
| 11362 | STAT1 | signal transducer and activator of transcription 1, 91kDa | 1 | STAT | |
| 6563 | LGALS3 | lectin, galactoside-binding, soluble, 3 | 1 | galectin 3 | |
| 12680 | VEGFA | vascular endothelial growth factor A | 1 | vascular endothelial growth factor | |
| 1662 | CD34 | CD34 molecule | 1 | CD34 | |
| 6886 | MAPK9 | mitogen-activated protein kinase 9 | 1 | SAPK | |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | 1 | p44 | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.6 | agent in this class and has been shown to enhance collagen solubility and to reduce expression of RAGE and AGE-R3 mRNA |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | VCAM-1 | 1.8 | VCAM-1 indicates vascular cell adhesion molecule ICAM intercellular adhesion molecule TF |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | IL-6 | 1.3 | adhesion molecule TF tissue factor AGE advanced glycation end product IL-6 interleukin-6 MCP-1 monocyte chemotactic protein-1 EC endothelial cell RBC red |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | MCP-1 | 2.0 | TF tissue factor AGE advanced glycation end product IL-6 interleukin-6 MCP-1 monocyte chemotactic protein-1 EC endothelial cell RBC red blood cell |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 0.9 | SOD superoxide dismutase |
| 4827 | HBB | hemoglobin, beta | hemoglobin | 1.0 | in vivo began in the mid-1970s with the study of hemoglobin A1c (HbA1c), HbA1c a naturally occurring minor human hemoglobin that |
| 4827 | HBB | hemoglobin, beta | hemoglobin | 1.0 | of hemoglobin A1c (HbA1c), HbA1c a naturally occurring minor human hemoglobin that is elevated in diabetic patients |
| 4827 | HBB | hemoglobin, beta | hemoglobin | 1.0 | the N-terminal valine amino group of the _amp_#223 chain of hemoglobin in which the glucose was thought to be attached via |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.0 | The thiamine monophosphate derivative benfotiamine inhibits hyperglycemia-dependent pathways and NF-kappaB activation and prevents experimental diabetic retinopathy |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.6 | N -carboxymethyl-lysine adducts are increased in soluble proteins and insoluble collagen in patients with diabetes and renal impairment |
| 21420 | CCRK | cell cycle related kinase | p42 | 0.3 | signaling pathways including p21ras erk 1/2 1 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 0.8 | pathways including p21ras erk 1/2 1 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho GTPases |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | p38 | 0.8 | p21ras erk 1/2 1 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho GTPases phosphoinositol-3 kinase |
| 6886 | MAPK9 | mitogen-activated protein kinase 9 | SAPK | 1.3 | 1 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho GTPases phosphoinositol-3 kinase and the JAK/STAT |
| 6881 | MAPK8 | mitogen-activated protein kinase 8 | JNK | 0.3 | 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho GTPases phosphoinositol-3 kinase and the JAK/STAT JAK |
| 6871 | MAPK1 | mitogen-activated protein kinase 1 | MAP | 0.8 | (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases rho GTPases phosphoinositol-3 kinase and the JAK/STAT JAK STAT |
| 2345 | CREB1 | cAMP responsive element binding protein 1 | CREB | 1.0 | JAK STAT pathway and downstream effectors such as NF-kappaB and CREB |
| 6877 | MAPK3 | mitogen-activated protein kinase 3 | p44 | 0.5 | multiple signaling pathways including p21ras erk 1/2 1 2 (p44/p42) p44 p42 MAP kinases p38 and SAPK/JNK SAPK JNK MAP kinases |
| 11362 | STAT1 | signal transducer and activator of transcription 1, 91kDa | STAT | 0.0 | MAP kinases rho GTPases phosphoinositol-3 kinase and the JAK/STAT JAK STAT pathway and downstream effectors such as NF-kappaB and CREB |
| 7794 | NFKB1 | nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105) | NF-kappaB | 0.0 | the JAK/STAT JAK STAT pathway and downstream effectors such as NF-kappaB and CREB |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | FGF2 | 2.5 | For example glycation of fibroblast growth factor 2 (FGF2) FGF2 lowered its chemotactic effect toward endothelial cells and when injected |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | FGF2 | 2.5 | toward endothelial cells and when injected in normoglycemic mice glycated FGF2 displayed a weaker angiogenic effect compared with nonglycated FGF2 |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | FGF2 | 2.5 | glycated FGF2 displayed a weaker angiogenic effect compared with nonglycated FGF2 |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | bFGF | 1.0 | Glycation of bFGF with the intracellular sugars fructose and glucose-6-phosphate reduced its high-affinity |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.6 | Endothelial cells cultured on matrices containing glycated collagen display a defect in branching angiogenesis in part by the |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | PAI-1 | 1.8 | in branching angiogenesis in part by the early induction of PAI-1 which is accompanied by a time-dependent reduction in cell proliferation |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen | 0.6 | Glycated collagen induces premature endothelial cell senescence as indicated by the appearance |
| 2197 | COL1A1 | collagen, type I, alpha 1 | collagen-induced | 0.3 | This glycated collagen-induced senescence is associated with a decreased synthesis of NO |
| 1662 | CD34 | CD34 molecule | CD34 | 0.6 | premise that progenitor cells may be impaired in diabetes cultured CD34 blood cells retrieved from type 1 diabetic subjects produced fewer |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | interleukin 6 | 1.0 | on endothelial cells ligation of receptor for age rage by ages induces the expression of cell adhesion molecules tissue factor cytokines such as interleukin 6 and monocyte chemoattractant protein 1. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemoattractant protein 1 | 1.0 | on endothelial cells ligation of receptor for age rage by ages induces the expression of cell adhesion molecules tissue factor cytokines such as interleukin 6 and monocyte chemoattractant protein 1. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | a chief means by which ages via rage exert their effects is by generation of reactive oxygen species at least in part via stimulation of nadph oxidase. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | mcp 1 | 1.0 | vcam 1 indicates vascular cell adhesion molecule; icam intercellular adhesion molecule; tf tissue factor; age advanced glycation end product; il 6 interleukin 6; mcp 1 monocyte chemotactic protein 1; ec endothelial cell; rbc red blood cell; rage receptor for age. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | interleukin 6 | 1.0 | vcam 1 indicates vascular cell adhesion molecule; icam intercellular adhesion molecule; tf tissue factor; age advanced glycation end product; il 6 interleukin 6; mcp 1 monocyte chemotactic protein 1; ec endothelial cell; rbc red blood cell; rage receptor for age. |
| 10618 | CCL2 | chemokine (C-C motif) ligand 2 | monocyte chemotactic protein 1 | 1.0 | vcam 1 indicates vascular cell adhesion molecule; icam intercellular adhesion molecule; tf tissue factor; age advanced glycation end product; il 6 interleukin 6; mcp 1 monocyte chemotactic protein 1; ec endothelial cell; rbc red blood cell; rage receptor for age. |
| 6018 | IL6 | interleukin 6 (interferon, beta 2) | il 6 | 1.0 | vcam 1 indicates vascular cell adhesion molecule; icam intercellular adhesion molecule; tf tissue factor; age advanced glycation end product; il 6 interleukin 6; mcp 1 monocyte chemotactic protein 1; ec endothelial cell; rbc red blood cell; rage receptor for age. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | nadph oxidase inhibitors: diphenyliodonium chloride dpi 4'hydroxy 3' methoxy acetophenone hmap . |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | sod: superoxide dismutase. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | oxidative reactions may be increased by oxidative stress arising from mitochondrial dysfunction and activation of nadph oxidase. |
| 4323 | GLO1 | glyoxalase I | glyoxalase i | 1.0 | incubation of gm7373 endothelial cells that stably express human glyoxalase i in high glucose concentration 30 micromol/l did not result in increased age formation whereas the age content in the nontransfected cells was increased 13.6 fold demonstrating that enzymatic defense |
| 4323 | GLO1 | glyoxalase I | glyoxalase i | 1.0 | oxidative stress is inextricably linked to glycation because the depletion of gsh and nadph also decreases the in situ activities of glyoxalase i and nadph dependent aldehyde reductases. |
| 5344 | ICAM1 | intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | intercellular adhesion molecule 1 | 1.0 | when endothelial cells undergo inflammatory activation the increased expression of selectins vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 may promote the adherence of monocytes. |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | when endothelial cells undergo inflammatory activation the increased expression of selectins vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 may promote the adherence of monocytes. |
| 12680 | VEGFA | vascular endothelial growth factor A | vascular endothelial growth factor | 1.0 | in reaction to hypoxemia induced microvascular damage the retinal epithelial and endothelial cells increase production of vascular endothelial growth factor and promote neoangiogenesis a process prevented by antibodies to rage. |
| 12663 | VCAM1 | vascular cell adhesion molecule 1 | vascular cell adhesion molecule 1 | 1.0 | the binding of ages to rage produces a local inflammatory reaction likely as a consequence of vascular cell adhesion molecule 1 overexpression leukocyte adhesion and cytokine release. |
| 14874 | NOX5 | NADPH oxidase, EF-hand calcium binding domain 5 | nadph oxidase | 1.0 | consistent with an important role for nadph oxidase in age rage triggered events macrophages derived from wild type mice expressed enhanced levels of tissue factor on stimulation with age. |
| 2578 | CYBB | cytochrome b-245, beta polypeptide (chronic granulomatous disease) | gp91 phox | 1.0 | in contrast macrophages derived from mice deficient in gp91 phox failed to display enhanced tissue factor on incubation with ages figure 3 . |
| 399 | ALB | albumin | albumin | 1.0 | postconfluent cultured endothelial cells incubated with red blood cells harvested from diabetic patients revealed increased diffusional transit permeability of macromolecular tracers i albumin and h inulin compared with endothelial cells incubated with red blood cells from nondiabetic subjects. |
| 3676 | FGF2 | fibroblast growth factor 2 (basic) | fibroblast growth factor 2 | 1.0 | for example glycation of fibroblast growth factor 2 fgf2 lowered its chemotactic effect toward endothelial cells and when injected in normoglycemic mice glycated fgf2 displayed a weaker angiogenic effect compared with nonglycated fgf2. |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | fgf2 | 1.0 | for example glycation of fibroblast growth factor 2 fgf2 lowered its chemotactic effect toward endothelial cells and when injected in normoglycemic mice glycated fgf2 displayed a weaker angiogenic effect compared with nonglycated fgf2. |
| 8053 | NUDT6 | nudix (nucleoside diphosphate linked moiety X)-type motif 6 | fgf2 | 1.0 | displayed a weaker angiogenic effect compared with nonglycated fgf2. |
| 8583 | SERPINE1 | serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1 | pai 1 | 1.0 | endothelial cells cultured on matrices containing glycated collagen display a defect in branching angiogenesis in part by the early induction of pai 1 which is accompanied by a time dependent reduction in cell proliferation. |
| 6563 | LGALS3 | lectin, galactoside-binding, soluble, 3 | galectin 3 | 1.0 | age r3 galectin 3 is proposed as a scavenger receptor because mice genetically devoid of age r3 develop a rapid glomerulosclerosis compared with wild type animals. |