)| PMID |
15863242 ( ) |
|---|---|
| Title | Proteome analysis in hippocampus of mice overexpressing human Cu/Zn-superoxide dismutase 1. |
| Abstract | Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in metabolism of oxygen free radicals and oxidative stress. Transgenic mice overexpressing human SOD1 (Tg-hSOD1) are useful model for Down syndrome (trisomy 21) and familial amyotrophic lateral sclerosis (ALS). It was shown recently that Tg-hSOD1 mice develop a characteristic set of neurodegenerative changes in hippocampus and we therefore decided to study differential protein expression patterns, constructing a mouse hippocampal proteome map using two-dimensional electrophoresis (2-DE) with in-gel digestion of spots followed by matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) identification and quantitatively compared protein profiles between non-transgenic mice, hemizygous and homozygous Tg-hSOD1 mice. In total 1056 spots were analysed, resulting in the identification of 445 polypeptides that were the products of 157 different genes. Among these a series of proteins involved in scaffolding, metabolism, signaling and other functions were deranged. Our findings suggest that overexpressed SOD1 directly or by generating reactive oxygen species may lead to aberrant protein expressional patterns that in turn may lead to or reflect neurodegeneration observed in this animal model. 18-20, 1090 Vienna, Austria. |
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)) | 48 | superoxide dismutase 1 | SOD1 | SOD1-mediated | hSOD1 | SOD1-dependent | mSOD1 | |
| 11655 | TCP1 | t-complex 1 | 4 | t complex 1 | TCP-1 | |
| 3013 | DPYS | dihydropyrimidinase | 3 | dihydropyrimidinase | |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | 2 | angiotensin ii | angiotensin i | |
| 3189 | EEF1A1 | eukaryotic translation elongation factor 1 alpha 1 | 2 | ef tu | EF-Tu-like | |
| 11517 | TAC1 | tachykinin, precursor 1 | 1 | substance p | |
| 17598 | UBE2J1 | ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog, yeast) | 1 | ubiquitin conjugating enzyme e2 | |
| 4605 | GRP | gastrin-releasing peptide | 1 | bombesin | |
| 1618 | CCT5 | chaperonin containing TCP1, subunit 5 (epsilon) | 1 | tcp 1 epsilon | |
| 12420 | TUFM | Tu translation elongation factor, mitochondrial | 1 | P43 | |
| 12408 | TUBA3C | tubulin, alpha 3c | 1 | tubulin alpha 2 | |
| 20778 | TUBB | tubulin, beta | 1 | tubulin beta polypeptide | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Cu/Zn-superoxide Cu Zn-superoxide dismutase 1 (SOD1), SOD1 encoded on chromosome 21 is a key enzyme in metabolism |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Transgenic mice overexpressing human SOD1 (Tg-hSOD1) Tg-hSOD1 are useful model for Down syndrome (trisomy trisomy |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Our findings suggest that overexpressed SOD1 directly or by generating reactive oxygen species may lead to |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | The human Cu/Zn-superoxide Cu Zn-superoxide dismutase 1 gene (hSOD1) hSOD1 was the first chromosome 21 gene to be characterised ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Later studies revealed overexpression of SOD1 mRNA protein and increased activity was detected in brains of |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Moreover transgenic mice expressing wild-type human SOD1 (Tg-hSOD1 Tg-hSOD1 mice were the first model for DS ( |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | deficit in DS no proof for a pathogenetic role of SOD1 in DS exists |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Although increased SOD1 may lead to generation of reactive oxygen species and thus |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | role in neurodegenerative mechanisms it was demonstrated that overexpression of SOD1 may be protective against apoptosis for hippocampal neurons ( Korenberg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | Transgenic mice about 3-month-old male harbouring the hSOD1 gene were obtained from Dr Jacqueline London University of Paris |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | Generation of the hSOD1 transgenic line KT has been described previously ( Paris et |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | by injecting an 11.5 kb EcoRI_amp_#x2013 BamH1 fragment containing the hSOD1 gene into fertilised eggs from FVB/N FVB N mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Measurement of SOD1 activity and immunostaining in WT and Tg-hSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | For hSOD1 activity measurements hippocampal extracts of WT and Tg-hSOD1 mice were |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Activity of SOD1 was assayed photochemically by measuring inhibition of nitroblue tetrazolium reduction |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | In Tg-hSOD1 mice immunostaining for hSOD1 was strong in the brain and no immunostaining occurred in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | the CNS of WT indicating that labeling was specific for hSOD1 ( Jaarsma et al. 2000 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Increased activity of SOD1 in hippocampus of Tg-hSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Overexpression of SOD1 in hippocampus was evaluated by enzymatic activity using the classic |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | the classic test of inhibition of nitroblue tetrazolium reduction by SOD1 and automatically assayed using a Ransod kit |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | The SOD1 activity was increased by factor 5 in blood |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | in hippocampus of 3-month-old Tg-SOD1 showed large increases in total SOD1 activity WT (2.5 2.5 _amp_#xb1 0.17 U/mg), U mg hemizygotes |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | WT (2.5 2.5 _amp_#xb1 0.17 U/mg), U mg hemizygotes (hSOD1/+, hSOD1 38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | hSOD1 38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1 hSOD1 47.79 _amp_#xb1 1.69 U/mg) U mg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | 38.87 _amp_#xb1 2.04 U/mg) U mg and homozygotes (hSOD1/hSOD1, hSOD1 hSOD1 47.79 _amp_#xb1 1.69 U/mg) U mg |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | large series of proteins were successfully represented and even transgenic hSOD1 was detected in 2-DE gels of Tg-hSOD1 mice ( Fig |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Antioxidant proteins showed no different expression except mouse SOD1 (mSOD1) mSOD1 (Unpublished Unpublished data Shin et al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | Antioxidant proteins showed no different expression except mouse SOD1 (mSOD1) mSOD1 (Unpublished Unpublished data Shin et al. 2003 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | In addition spots of mSOD1 and hSOD1 showing high similarity ( Fig 3 (A)) A |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | In addition spots of mSOD1 and hSOD1 showing high similarity ( Fig 3 (A)) A were detected |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | We observed that expression level of hSOD1 in hippocampus of homozygotes was significantly higher than that in |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | _amp_#xb1 1.804 versus 12.244 _amp_#xb1 2.259 P = 0.0259 while mSOD1 was significantly decreased in hippocampus of Tg-hSOD1 mice (Unpublished Unpublished |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-dependent | 1.7 | in hemizygous or homozygous Tg-hSOD1 mice revealing directly or indirectly SOD1-dependent alterations of several protein pathways and cascades systems that are |
| 11655 | TCP1 | t-complex 1 | TCP-1 | 1.3 | Eight t-complex 1 proteins (TCP-1) TCP-1 were studied in DS brain the TCP-1 epsilon ( Yoo |
| 11655 | TCP1 | t-complex 1 | TCP-1 | 1.3 | 1 proteins (TCP-1) TCP-1 were studied in DS brain the TCP-1 epsilon ( Yoo et al. 2001a as well as alpha |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | the gamma subunit was here observed in hippocampus in the SOD1 overexpression animal model of DS |
| 11655 | TCP1 | t-complex 1 | TCP-1 | 1.3 | Alterations of the TCP-1 system are of particular interest as some subunits are chaperones |
| 3189 | EEF1A1 | eukaryotic translation elongation factor 1 alpha 1 | EF-Tu-like | 2.1 | of translation reflected by reduced expression of translation elongation factor EF-Tu-like protein P43 ( Table 2 |
| 12420 | TUFM | Tu translation elongation factor, mitochondrial | P43 | 1.4 | reflected by reduced expression of translation elongation factor EF-Tu-like protein P43 ( Table 2 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1-mediated | 2.0 | catalyzing covalent attachment of ubiquitin to other proteins may reflect SOD1-mediated impaired protein handling in terms of ubiquitination |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | SOD1 | 2.5 | Multiple protein derangement may directly or indirectly depend on SOD1 overexpression impairment of translation (translation translation elongation or simply reflect |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | Spots of mSOD1 and hSOD1 were demonstrated in hippocampus of Tg-hSOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | Spots of mSOD1 and hSOD1 were demonstrated in hippocampus of Tg-hSOD1 mice |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | Fig 3._amp_#xa0 Comparison of hSOD1 with mSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | Fig 3._amp_#xa0 Comparison of hSOD1 with mSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | (A) A Alignment of hSOD1 (P00441) P00441 with mSOD1 ( P08228 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | (A) A Alignment of hSOD1 (P00441) P00441 with mSOD1 ( P08228 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | This sequence alignment with CLUSTALW showed that hSOD1 has high similarity to mSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | alignment with CLUSTALW showed that hSOD1 has high similarity to mSOD1 |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | mSOD1 | 1.7 | MALDI-TOF spectrum of mSOD1 (B) B and hSOD1 (C) C |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | hSOD1 | 3.0 | MALDI-TOF spectrum of mSOD1 (B) B and hSOD1 (C) C |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | cu/zn superoxide dismutase 1 sod1 encoded on chromosome 21 is a key enzyme in metabolism of oxygen free radicals and oxidative stress. |
| 11179 | SOD1 | superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult)) | superoxide dismutase 1 | 1.0 | the human cu/zn superoxide dismutase 1 gene hsod1 was the first chromosome 21 gene to be characterised groner et al. 1985 and it was even shown earlier to be overexpressed at the protein level in down syndrome ds; trisomy 21 patients sine |
| 11517 | TAC1 | tachykinin, precursor 1 | substance p | 1.0 | calibration of the instrument was performed externally with [m + h] + ions of angiotensin i angiotensin ii substance p bombesin and adrenocorticotropic hormones clip 1_amp_#x2013;17 and clip 18_amp_#x2013;39 . |
| 4605 | GRP | gastrin-releasing peptide | bombesin | 1.0 | calibration of the instrument was performed externally with [m + h] + ions of angiotensin i angiotensin ii substance p bombesin and adrenocorticotropic hormones clip 1_amp_#x2013;17 and clip 18_amp_#x2013;39 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin i | 1.0 | calibration of the instrument was performed externally with [m + h] + ions of angiotensin i angiotensin ii substance p bombesin and adrenocorticotropic hormones clip 1_amp_#x2013;17 and clip 18_amp_#x2013;39 . |
| 333 | AGT | angiotensinogen (serpin peptidase inhibitor, clade A, member 8) | angiotensin ii | 1.0 | calibration of the instrument was performed externally with [m + h] + ions of angiotensin i angiotensin ii substance p bombesin and adrenocorticotropic hormones clip 1_amp_#x2013;17 and clip 18_amp_#x2013;39 . |
| 1618 | CCT5 | chaperonin containing TCP1, subunit 5 (epsilon) | tcp 1 epsilon | 1.0 | eight t complex 1 proteins tcp 1 were studied in ds brain; the tcp 1 epsilon yoo et al. 2001a as well as alpha and beta subunits were significantly decreased in fetal second trimester ds brain yoo et al. 2001b and decrease of the gamma subunit was here observed in hippocampus |
| 11655 | TCP1 | t-complex 1 | t complex 1 | 1.0 | eight t complex 1 proteins tcp 1 were studied in ds brain; the tcp 1 epsilon yoo et al. 2001a as well as alpha and beta subunits were significantly decreased in fetal second trimester ds brain yoo et al. 2001b and dec |
| 12408 | TUBA3C | tubulin, alpha 3c | tubulin alpha 2 | 1.0 | while reduced neurofilament triplet m protein and neuronal tropomodulin markers for neuronal density may simply indicate neuronal loss in brain of transgenic animals tubulin alpha 2 and beta chains were overexpressed in this study ruling out that decrease of proteins in this study was simply due to neuronal loss. |
| 3189 | EEF1A1 | eukaryotic translation elongation factor 1 alpha 1 | ef tu | 1.0 | species ros with subsequent oxidation and modification of transcription neurodegeneration per se or general impairment of translation reflected by reduced expression of translation elongation factor ef tu like protein p43 table 2 . |
| 3013 | DPYS | dihydropyrimidinase | dihydropyrimidinase | 1.0 | a most intriguing finding was misexpression of dihydropyrimidinase related proteins major neuronal migration guidance cues in tg hsod1 mice: pathfinding of growing axons to reach their target during brain development or modeling is a subtle process needed to build u |
| 3013 | DPYS | dihydropyrimidinase | dihydropyrimidinase | 1.0 | abnormal brain development in ds was described in a couple of morphological reports becker et al. 1991 epstein 1995 wisniewski and bobinski 1991 and wisniewski and kida 1994 and decrease of dihydropyrimidinase related protein 2 in ds was previously observed weitzdoerfer et al. 2001a and weitzdoerfer et al. 2001b . |
| 3013 | DPYS | dihydropyrimidinase | dihydropyrimidinase | 1.0 | expressional patterns of several dihydropyrimidinase related proteins including isoforms or posttranslational modifications thereof in tg hsod1 mice and in ds were similar and may represent or lead to neurodegenerative changes abnormal wiring and plast |
| 17598 | UBE2J1 | ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog, yeast) | ubiquitin conjugating enzyme e2 | 1.0 | finally the manifold decrease of ubiquitin conjugating enzyme e2 level in tg hsod1 mice catalyzing covalent attachment of ubiquitin to other proteins may reflect sod1 mediated impaired protein handling in terms of ubiquitination. |
| 20778 | TUBB | tubulin, beta | tubulin beta polypeptide | 1.0 | we have included fragments of two proteins table 1 similar to tubulin beta polypeptide and sex determining protein that were differentially expressed between groups but these were not included in the discussion as no definitive assignment can be made based upon an incomplete sequence. |