)| PMID |
16043017 ( ) |
|---|---|
| Title | Redox proteomics analysis of oxidatively modified proteins in G93A-SOD1 transgenic mice--a model of familial amyotrophic lateral sclerosis. |
| Abstract | Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron degenerative disease characterized by the loss of neuronal function in the motor cortex, brain stem, and spinal cord. Familial ALS cases, accounting for 10-15% of all ALS disease, are caused by a gain-of-function mutation in Cu,Zn-superoxide dismutase (SOD1). Two hypotheses have been proposed to explain the toxic gain of function of mutant SOD (mSOD). One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species generation, whereas the other hypothesis suggests that mSODs are prone to aggregation due to instability or association with other proteins. However, the hypotheses of oxidative stress and protein aggregation are not mutually exclusive. G93A-SOD1 transgenic mice show significantly increased protein carbonyl levels in their spinal cord from 2 to 4 months and eventually develop ALS-like motor neuron disease and die within 5-6 months. Here, we used a parallel proteomics approach to investigate the effect of the G93A-SOD1 mutation on protein oxidation in the spinal cord of G93A-SOD1 transgenic mice. Four proteins in the spinal cord of G93A-SOD1 transgenic mice have higher specific carbonyl levels compared to those of non-transgenic mice. These proteins are SOD1, translationally controlled tumor protein (TCTP), ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), and, possibly, alphaB-crystallin. Because oxidative modification can lead to structural alteration and activity decline, our current study suggests that oxidative modification of UCH-L1, TCTP, SOD1, and possibly alphaB-crystallin may play an important role in the neurodegeneration of ALS. |
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 |
|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | 46 | SOD1 | SOD1-related | mSOD1 | SOD1-linked | SOD | superoxide dismutase | mSOD | |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | 42 | uch l1 | UCH-L1 | |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | 17 | TCTP | |
| 10417 | RPS27A | ribosomal protein S27a | 7 | ubiquitin | |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | 3 | TNF--modulating | tumor necrosis factor | TNF- | |
| 12609 | USP11 | ubiquitin specific peptidase 11 | 2 | ubiquitin carboxyl terminal hydrolase | |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | 2 | HSPs | |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | 1 | glutamine synthetase | |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | 1 | nitric oxide synthase | |
| 12468 | UBC | ubiquitin C | 1 | ubiquitin c | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | caused by a gain-of-function mutation in Cu Zn-superoxide dismutase (SOD1) SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | proposed to explain the toxic gain of function of mutant SOD (mSOD) mSOD |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | explain the toxic gain of function of mutant SOD (mSOD) mSOD |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | These proteins are SOD1 translationally controlled tumor protein (TCTP), TCTP ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | These proteins are SOD1 translationally controlled tumor protein (TCTP), TCTP ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), UCH-L1 and possibly B-crystallin |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | translationally controlled tumor protein (TCTP), TCTP ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1), UCH-L1 and possibly B-crystallin |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | activity decline our current study suggests that oxidative modification of UCH-L1 TCTP SOD1 and possibly B-crystallin may play an important role |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | decline our current study suggests that oxidative modification of UCH-L1 TCTP SOD1 and possibly B-crystallin may play an important role in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | our current study suggests that oxidative modification of UCH-L1 TCTP SOD1 and possibly B-crystallin may play an important role in the |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | caused by a gain-of-function mutation in Cu Zn-superoxide dismutase (SOD1) SOD1 3 and 4 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | SOD1 catalyzes the disproportionation of superoxide anion radical to hydrogen peroxide |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Over 100 different missense substitutions in the 153-amino-acid SOD1 have been described in individuals and kindreds affected by SOD1-linked |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-linked | 1.9 | SOD1 have been described in individuals and kindreds affected by SOD1-linked FALS 5 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | One of the most common mutations of SOD1 is the substitution of glycine by alanine at residue 93 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | proposed to explain the toxic gain of function of mutant SOD (mSOD) mSOD 6 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | explain the toxic gain of function of mutant SOD (mSOD) mSOD 6 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | One is that mSOD can directly promote reactive oxygen species and reactive nitrogen species |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | in tissues from ALS patients 23 24 and 25 and mSOD transgenic mice 22 and 26 reportedly are rich in mSOD |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | mSOD transgenic mice 22 and 26 reportedly are rich in mSOD ubiquitin and neurofilament proteins |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-related | 1.9 | oxidative modification of macromolecules was demonstrated in neuronal tissues of SOD1-related FALS patients and transgenic mice 30 31 and 32 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | Enhanced susceptibility of exogenous oxidative stress in mSOD1 cell cultures was also observed in in vitro studies 33 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD | 1.9 | Exogenous oxidative stress can even inhibit the rapid degradation of mSOD 36 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | higher capacity to generate free radicals 9 compared to wild-type SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | of the oxidatively modified proteins in G93A-SOD1 transgenic mice is SOD1 32 indicating that oxidation of SOD1 is likely important to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | G93A-SOD1 transgenic mice is SOD1 32 indicating that oxidation of SOD1 is likely important to the development of this model of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Transgenic mice expressing the human SOD1 gene with a G93A mutation strain B6SJL/TgN B6SJL TgN (SOD1-G93A)-2Gur) |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) UCH-L1 assay |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | The activities of UCH-L1 in the spinal cord were measured by determining the rate |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | UCH-L1 activities of each individual were assayed by the change of |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | The average UCH-L1 activities of six transgenic animals were compared to those of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | These proteins were identified as SOD1 translationally controlled tumor protein (TCTP), TCTP UCH-L1 and B-crystallin |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | proteins were identified as SOD1 translationally controlled tumor protein (TCTP), TCTP UCH-L1 and B-crystallin |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | were identified as SOD1 translationally controlled tumor protein (TCTP), TCTP UCH-L1 and B-crystallin |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | We report here that the specific carbonyl levels of human SOD1 TCTP UCH-L1 and possibly B-crystallin are significantly increased in the |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | report here that the specific carbonyl levels of human SOD1 TCTP UCH-L1 and possibly B-crystallin are significantly increased in the spinal |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | here that the specific carbonyl levels of human SOD1 TCTP UCH-L1 and possibly B-crystallin are significantly increased in the spinal cord |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Spots close to human SOD1 are modified SOD1 possibly phosphorylated SOD1 |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | oxidative modification inactivated protein activity we compared the activity of UCH-L1 in the G93A-SOD1 transgenic mice to that in the control |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | of activity of oxidatively modified proteins 49 50 and 51 UCH-L1 activity was significantly decreased (29%) 29% in the G93A-SOD1 transgenic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD | 1.9 | provide insight into the mechanisms of the neurotoxicity of mutant SOD in vivo |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | It is well established that mutant SOD1 enhances oxidative activity by acting as a peroxidase 9 11 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | carbonyl levels compared to those of the nontransgenic mice as SOD1 TCTP UCH-L1 and B-crystallin |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | levels compared to those of the nontransgenic mice as SOD1 TCTP UCH-L1 and B-crystallin |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | compared to those of the nontransgenic mice as SOD1 TCTP UCH-L1 and B-crystallin |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | SOD1 previously was identified immunochemically as one of the oxidatively modified |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | proteomics approach to confirm that the specific carbonyl level of SOD1 is increased in the spinal cords of G93A-SOD1 transgenic mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Although G93A-SOD1 shows dismutation activity identical to that of wild-type SOD1 the activity of SOD1 in FALS patients with mutations is |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | activity identical to that of wild-type SOD1 the activity of SOD1 in FALS patients with mutations is decreased 50% in motor |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | radical production in the G93A-SOD1 transgenic animals is induced by SOD1 mutation 32 alteration of tumor necrosis factor TNF- and TNF--modulating |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF- | 1.2 | induced by SOD1 mutation 32 alteration of tumor necrosis factor TNF- and TNF--modulating cytokines 38 and 46 |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | TNF--modulating | 1.2 | SOD1 mutation 32 alteration of tumor necrosis factor TNF- and TNF--modulating cytokines 38 and 46 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | study is consistent with the notion that oxidative modification of SOD1 plays a role in the neurotoxicity of mutant SOD1 in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | of SOD1 plays a role in the neurotoxicity of mutant SOD1 in the disease |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | modified protein in G93A-SOD1 transgenic mice identified by proteomics was TCTP |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | TCTP processes calcium-binding activity (reviewed reviewed in 55 and has a |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | Overexpression of TCTP stabilizes microtubules and alters cell morphology 57 |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | Other molecular interactions of TCTP include self-interaction 58 and the interaction with myeloid cell leukemia |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | TCTP levels are highly regulated in response to various stress conditions |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | characterization as an antiapoptotic protein 67 these observations suggest that TCTP may exert a cytoprotective function for cells |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | The current study showed that TCTP was oxidatively modified in the spinal cord of G93A-SOD1 mice |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | the putative cytoprotective function and the calcium binding affinity of TCTP are impaired in G93A-SOD1 mice because oxidative modification alters the |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | lymphocytes from ALS patients 70 suggesting that oxidative modification of TCTP may also play an important role in neurotoxicity of G93A-SOD1 |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | UCH-L1 belongs to a family of ubiquitin carboxyl-terminal hydrolases that play |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | Loss of UCH-L1 function causes neuroaxonal dystrophy 74 75 and 76 significant protein |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | Similarly decreased UCH-L1 activity by mutation also enhances protein aggregation in Escherichia coli |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | Therefore based on the prior literature oxidative inactivation of UCH-L1 presented in the current study possibly contributes to both the |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | notion and consistent with our finding ( Fig 4 that UCH-L1 activity is decreased in G93A-SOD1 mouse spinal cord the inclusions |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.9 | G93A-SOD1 mouse spinal cord the inclusions of human ALS and mSOD1 (including including G93A mice are excessively ubiquitinated 79 80 81 |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 1.2 | HSPs are cellular constituents synthesized by living organisms under stress conditions |
| 5232 | HSPA1A | heat shock 70kDa protein 1A | HSPs | 1.2 | to stabilize other proteins under stress conditions whereas the high-molecular-weight HSPs normally play roles in protein folding during biosynthesis 83 and |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | remarkable feature of the oxidatively modified proteins (except except for TCTP in G93A-SOD1 transgenic mice is that they are involved in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Aberrant accumulation of mutant SOD1 is demonstrated in Caenorhabditis elegans expressing human mutant SOD1 36 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | mutant SOD1 is demonstrated in Caenorhabditis elegans expressing human mutant SOD1 36 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | Based on our current observations the increased oxidative modification of SOD1 UCH-L1 and B-crystallin plays a significant role in the protein |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | on our current observations the increased oxidative modification of SOD1 UCH-L1 and B-crystallin plays a significant role in the protein aggregation |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | involves oxidative modification of a Ca 2 regulating protein (TCTP) TCTP and proteins involved in inclusion formation (SOD1, SOD1 UCH-L1 and |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | protein (TCTP) TCTP and proteins involved in inclusion formation (SOD1, SOD1 UCH-L1 and B-crystallin suggesting a potential relationship between protein oxidation |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | (TCTP) TCTP and proteins involved in inclusion formation (SOD1, SOD1 UCH-L1 and B-crystallin suggesting a potential relationship between protein oxidation protein |
| 12022 | TPT1 | tumor protein, translationally-controlled 1 | TCTP | 2.5 | proteins impairs protein stability ( B-crystallin Ca 2 binding (TCTP), TCTP protein degradation (UCH-L1), UCH-L1 and antioxidant capacity (SOD1) SOD1 |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | ( B-crystallin Ca 2 binding (TCTP), TCTP protein degradation (UCH-L1), UCH-L1 and antioxidant capacity (SOD1) SOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.7 | (TCTP), TCTP protein degradation (UCH-L1), UCH-L1 and antioxidant capacity (SOD1) SOD1 |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | Fig 4._amp_#xa0 Activity of UCH-L1 in G93A-SOD1 transgenic mice as a percentage of the nontransgenic |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | UCH-L1 | 2.2 | The activity of UCH-L1 is significantly decreased in the spinal cord of G93A-SOD1 transgenic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | familial als cases accounting for 10_amp_#x2013;15% of all als disease are caused by a gain of function mutation in cu zn superoxide dismutase sod1 . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | these proteins are sod1 translationally controlled tumor protein tctp ubiquitin carboxyl terminal hydrolase l1 uch l1 and possibly b crystallin. |
| 12609 | USP11 | ubiquitin specific peptidase 11 | ubiquitin carboxyl terminal hydrolase | 1.0 | these proteins are sod1 translationally controlled tumor protein tctp ubiquitin carboxyl terminal hydrolase l1 uch l1 and possibly b crystallin. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | these proteins are sod1 translationally controlled tumor protein tctp ubiquitin carboxyl terminal hydrolase l1 uch l1 and possibly b crystallin. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | because oxidative modification can lead to structural alteration and activity decline our current study suggests that oxidative modification of uch l1 tctp sod1 and possibly b crystallin may play an important role in the neurodegeneration of als. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase | 1.0 | inherited als accounts for 10_amp_#x2013;15% of cases and among all of the familial als fals patients 20_amp_#x2013;30% of them are caused by a gain of function mutation in cu zn superoxide dismutase sod1 [3] and [4] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | the proteinaceous inclusions found in tissues from als patients [23] [24] and [25] and msod transgenic mice [22] and [26] reportedly are rich in msod ubiquitin and neurofilament proteins. |
| 7873 | NOS2A | nitric oxide synthase 2A (inducible, hepatocytes) | nitric oxide synthase | 1.0 | also elevation of inflammation related genes e.g. induced nitric oxide synthase proinflammatory cytokines occurs at 11 weeks of age in the presymptomatic stage before motor neuron death in g93a sod1 transgenic mice suggesting that neuroinflammation mediated oxidative stress is a |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | ubiquitin carboxyl terminal hydrolase l1 uch l1 assay |
| 12609 | USP11 | ubiquitin specific peptidase 11 | ubiquitin carboxyl terminal hydrolase | 1.0 | ubiquitin carboxyl terminal hydrolase l1 uch l1 assay |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | ubiquitin carboxyl terminal hydrolase l1 uch l1 assay |
| 12468 | UBC | ubiquitin C | ubiquitin c | 1.0 | the activities of uch l1 in the spinal cord were measured by determining the rate of conversion of ubiquitin c terminal 7 amido 4 methylcoumarin ub amc calbiochem to ubiquitin and free amc [48] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | the activities of uch l1 in the spinal cord were measured by determining the rate of conversion of ubiquitin c terminal 7 amido 4 methylcoumarin ub amc calbiochem to ubiquitin and free amc [48] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | uch l1 activities of each individual were assayed by the change of _amp_#x3bb; em 460 nm over time. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | the average uch l1 activities of six transgenic animals were compared to those of six control animals using student's t test. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | these proteins were identified as sod1 translationally controlled tumor protein tctp uch l1 and b crystallin. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | we report here that the specific carbonyl levels of human sod1 tctp uch l1 and possibly b crystallin are significantly increased in the spinal cord of g93a sod1 transgenic mice compared to that of nontransgenic mice. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | in order to confirm that oxidative modification inactivated protein activity we compared the activity of uch l1 in the g93a sod1 transgenic mice to that in the control mice. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | consistent with our prior studies that demonstrate loss of activity of oxidatively modified proteins [49] [50] and [51] uch l1 activity was significantly decreased 29% in the g93a sod1 transgenic mice compared to that of nontransgenic control fig 4 . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | in the current study we identified the proteins that demonstrate increased carbonyl levels compared to those of the nontransgenic mice as sod1 tctp uch l1 and b crystallin. |
| 11892 | TNF | tumor necrosis factor (TNF superfamily, member 2) | tumor necrosis factor | 1.0 | moreover free radical production in the g93a sod1 transgenic animals is induced by sod1 mutation [32] alteration of tumor necrosis factor tnf and tnf modulating cytokines [38] and [46] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | uch l1 belongs to a family of ubiquitin carboxyl terminal hydrolases that play important roles in the ubiquitin_amp_#x2013;proteolytic pathway [71] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | uch l1 belongs to a family of ubiquitin carboxyl terminal hydrolases that play important roles in the ubiquitin_amp_#x2013;proteolytic pathway [71] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | uch ls then recycle ubiquitin from ubiquitinated protein complexes or polyubiquitin chains by cleaving the amide linkage next to the c terminal glycine of ubiquitin [72] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | loss of uch l1 function causes neuroaxonal dystrophy [74] [75] and [76] significant protein oxidization [45] and accumulation of synuclein protein in gracile axonal dystrophy mice [77] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | similarly decreased uch l1 activity by mutation also enhances protein aggregation in escherichia coli [78] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | therefore based on the prior literature oxidative inactivation of uch l1 presented in the current study possibly contributes to both the protein aggregation and the oxidative stress observed in g93a sod1 transgenic mice and als patients. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | consistent with this notion and consistent with our finding fig 4 that uch l1 activity is decreased in g93a sod1 mouse spinal cord the inclusions of human als and msod1 including g93a mice are excessively ubiquitinated [79] [80] [81] and [82] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | moreover crystallins were recruited to aggregates when cells were treated with proteasome inhibitor [88] and the degradation of b crystallin along with ubiquitin conjugation was decreased in bovine lens epithelial cells when b crystallin was oxidized [89] . |
| 4341 | GLUL | glutamate-ammonia ligase (glutamine synthetase) | glutamine synthetase | 1.0 | consistent with this notion inclusions in als patients contain b crystallin metallothionein glutamine synthetase and tubulin immunoreactivities [90] . |
| 10417 | RPS27A | ribosomal protein S27a | ubiquitin | 1.0 | ubiquitin protein epitopes and b crystallin are found in fibrillar neuronal inclusions in the cortex of sporadic als patients [79] [80] [81] and [91] . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | based on our current observations the increased oxidative modification of sod1 uch l1 and b crystallin plays a significant role in the protein aggregation in the spinal cords of g93a sod1 transgenic mice. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | study provides insight into the mechanism of g93a sod1 neurotoxicity in vivo which involves oxidative modification of a ca 2+ regulating protein tctp and proteins involved in inclusion formation sod1 uch l1 and b crystallin suggesting a potential relationship between protein oxidation protein aggregation and ca 2+ regulation in als. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | moreover one can speculate that the oxidative modification of these proteins impairs protein stability b crystallin ca 2+ binding tctp protein degradation uch l1 and antioxidant capacity sod1 . |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | fig. 4._amp_#xa0;activity of uch l1 in g93a sod1 transgenic mice as a percentage of the nontransgenic control. |
| 12513 | UCHL1 | ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase) | uch l1 | 1.0 | the activity of uch l1 is significantly decreased in the spinal cord of g93a sod1 transgenic mice compared to nontransgenic control. |