)| PMID |
11978481 ( ) |
|---|---|
| Title | Oxidatively modified proteins in aging and disease. |
| Abstract | There is a large body of evidence implicating oxidative damage in the pathogenesis of both normal aging and neurodegenerative diseases. Oxidative damage to proteins has been well established. Although there are a large number of potential oxidative modifications only a few have been systematically studied. The most frequently studied marker of oxidative damage to proteins is protein carbonyl groups. 3-Nitrotyrosine is thought to be a relatively specific marker of oxidative damage mediated by peroxynitrite. Increased concentrations of both protein carbonyls and 3-nitrotyrosine have been documented in both normal aging as well as in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). These findings help to provide a rationale for trials of antioxidants in neurodegenerative diseases. University, New York Presbyterian Hospital, New York, NY 10021, USA. fbeal@mail.med.cornell.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 |
|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | 9 | NOS | nNOS | neuronal nitric oxide synthase | |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | 4 | manganese superoxide dismutase | |
| 1991 | CKB | creatine kinase, brain | 4 | creatine kinase | |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | 3 | glutamine synthetase | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 3 | iNOS | nitric oxide synthase | |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 2 | amyloid | |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | 2 | endothelial nitric oxide synthase | eNOS | |
| 6893 | MAPT | microtubule-associated protein tau | 2 | microtubule associated protein tau | |
| 118 | ACO2 | aconitase 2, mitochondrial | 1 | aconitase | |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | 1 | heme oxygenase 1 | |
| 14133 | SEPX1 | selenoprotein X, 1 | 1 | methionine sulfoxide reductase | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.7 | isoforms of nitric oxide synthase neuronal nitric oxide synthase (nNOS), nNOS endothelial nitric oxide synthase (eNOS), eNOS and inducible nitric oxide |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | eNOS | 2.2 | nitric oxide synthase (nNOS), nNOS endothelial nitric oxide synthase (eNOS), eNOS and inducible nitric oxide synthase (iNOS) iNOS |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | iNOS | 2.7 | oxide synthase (eNOS), eNOS and inducible nitric oxide synthase (iNOS) iNOS |
| 118 | ACO2 | aconitase 2, mitochondrial | aconitase | 1.3 | immunochemical probe for oxidative damage it was demonstrated that mitochondrial aconitase was particularly vulnerable to oxidative damage accompanying aging in drosophila |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | The neuropathologic hallmarks are senile plaques containing _amp_#x3b2 -amyloid and neurofibrillary tangles which occur in pyramidal neurons of the |
| 6893 | MAPT | microtubule-associated protein tau | tau | 2.7 | aggregates which are largely made up of the microtubule-associated protein tau |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 1.0 | Histochemical methods showed 4-hydroxynonenal staining of amyloid deposits 32 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | NOS | 2.7 | 3-nitrotyrosine generation are also attenuated in mice deficient in inducible NOS 48 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.7 | An increase in neuronal nitric oxide synthase (nNOS) nNOS was found in motor neurons in one study 65 66 |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.7 | Other recent studies showed no alteration in nNOS in motor neurons but showed an increase in nNOS in |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | nNOS | 2.7 | in nNOS in motor neurons but showed an increase in nNOS in reactive astrocytes in ALS spinal cord and subcortical white |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | the generation of nitric oxide no _amp_#x2022; from arginine by nitric oxide synthase is a process which is involved in neurotransmission regulation of vascular relaxation and in inflammatory processes. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | the generation of no _amp_#x2022; is catalyzed by three isoforms of nitric oxide synthase neuronal nitric oxide synthase nnos endothelial nitric oxide synthase enos and inducible nitric oxide synthase inos . |
| 7876 | NOS3 | nitric oxide synthase 3 (endothelial cell) | endothelial nitric oxide synthase | 1.0 | the generation of no _amp_#x2022; is catalyzed by three isoforms of nitric oxide synthase neuronal nitric oxide synthase nnos endothelial nitric oxide synthase enos and inducible nitric oxide synthase inos . |
| 14133 | SEPX1 | selenoprotein X, 1 | methionine sulfoxide reductase | 1.0 | recent work showed that transgenic mice with a knockout of methionine sulfoxide reductase which repairs oxidized methione have a reduced life span and show increased protein carbonyls [ 17 ]. |
| 1991 | CKB | creatine kinase, brain | creatine kinase | 1.0 | prior studies showed that glutamine synthetase and creatine kinase are particularly vulnerable to oxidative damage [ 12 and 20 ]. |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | glutamine synthetase | 1.0 | prior studies showed that glutamine synthetase and creatine kinase are particularly vulnerable to oxidative damage [ 12 and 20 ]. |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | manganese superoxide dismutase | 1.0 | one protein was manganese superoxide dismutase which was previously shown to be selectively nitrated at tyr 34 and inactivated [ 22 ]. |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | glutamine synthetase | 1.0 | nitration of tyrosine residues in glutamine synthetase by peroxynitrite inhibits oxidation of methione residues and leads to inactivation of the enzyme [ 3 ]. |
| 1991 | CKB | creatine kinase, brain | creatine kinase | 1.0 | creatine kinase is another key intracellular enzyme regulating energy metabolism that is nitrated and inactivated by peroxynitrite [ 25 ]. |
| 1991 | CKB | creatine kinase, brain | creatine kinase | 1.0 | there were also significant decreases in glutamine synthetase and creatine kinase activity and alterations in spin labeled synaptosomes consistent with oxidative damage. |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | glutamine synthetase | 1.0 | there were also significant decreases in glutamine synthetase and creatine kinase activity and alterations in spin labeled synaptosomes consistent with oxidative damage. |
| 6893 | MAPT | microtubule-associated protein tau | microtubule associated protein tau | 1.0 | neurofibrillary tangles are protein aggregates which are largely made up of the microtubule associated protein tau. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | the source of the nitric oxide is possibly from upregulation of an inducible nitric oxide synthase in neurofibrillary tangle bearing neurons or from nitric oxide synthase in astrocytes and microglia adjacent to senile plaques [ 38 and 39 ]. |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | manganese superoxide dismutase | 1.0 | a 6 fold increase in 3 nitrotyrosine concentrations was detected in ad cerebrospinal fluid as compared to age matched controls [ 41 ] and an increase in nitrated manganese superoxide dismutase was also reported [ 42 ]. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | we and others showed that inhibitors of neuronal nitric oxide synthase blocked mptp induced dopaminergic toxicity in mice and that mptp neurotoxicity was attenuated in mice deficient in neuronal nitric oxide synthase [ 45 and 46 ]. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | we subsequently showed that neuronal nitric oxide synthase inhibitors blocked mptp neurotoxicity in baboons and this was accompanied by an inhibition of 3 nitrotyrosine staining [ 47 ]. |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | manganese superoxide dismutase | 1.0 | an increase in nitrated manganese superoxide dismutase was found in cerebrospinal fluid [ 42 ]. |
| 5013 | HMOX1 | heme oxygenase (decycling) 1 | heme oxygenase 1 | 1.0 | other evidence for oxidative damage to proteins in pd is increased expression of neural heme oxygenase 1 and increased immunostaining of glycosylated proteins [ 55 and 56 ]. |
| 11180 | SOD2 | superoxide dismutase 2, mitochondrial | manganese superoxide dismutase | 1.0 | other groups reported marked increases of both free 3 nitrotyrosine and nitrated manganese superoxide dismutase in the cerebrospinal fluid of sporadic als patients [ 42 and 62 ]. |
| 1991 | CKB | creatine kinase, brain | creatine kinase | 1.0 | we found significant decreases in creatine kinase activity in the transgenic als mice that were mimicked by exposure of brain extracts of peroxynitrite [ 63 ]. |
| 7872 | NOS1 | nitric oxide synthase 1 (neuronal) | neuronal nitric oxide synthase | 1.0 | an increase in neuronal nitric oxide synthase nnos was found in motor neurons in one study [ 65 66 and 67 ]. |