Document Information

PMID 14648077  (  )
Title Histological evidence of redox system breakdown caused by superoxide dismutase 1 (SOD1) aggregation is common to SOD1-mutated motor neurons in humans and animal models.
Abstract Living cells produce reactive oxygen species (ROSs). To protect themselves from these ROSs, the cells have developed both an antioxidant system containing superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2, thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts superoxide radicals into hydrogen peroxide (H2O2), and H2O2 is then converted into harmless water (H2O) and oxygen (O2) by Prx2 and GPx1 that directly regulate the redox system. To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an Ala-->Val substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1: the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident. Based on the fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1. of Medicine, Tottori University, Nishi-cho 36-1, 683-8504 Yonago, Japan. kato@grape.med.tottori-u.ac.jp

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))114superoxide dismutase 1 | SOD1 | SOD1-linked | SOD | SOD1-related | SOD1-mediated | SOD1-positive | superoxide dismutase1 | SOD1-mutated |
9353PRDX2peroxiredoxin 2110peroxiredoxin 2 | Prx2-immunostaining | thioredoxin peroxidase 1 | thioredoxin dependent peroxide reductase 1 | peroxiredoxin2 |
4553GPX1glutathione peroxidase 179glutathione peroxidase1 | glutathione peroxidase 1 | GPx1-immunoreactive | GPx1-positive |
16753PRDX6peroxiredoxin 64Prx |
399ALBalbumin3serum albumin |
1516CATcatalase2catalase |
11181SOD3superoxide dismutase 3, extracellular2SOD3 |
1613CCScopper chaperone for superoxide dismutase2CCS-mutant |
12435TXNthioredoxin2thioredoxin |
6893MAPTmicrotubule-associated protein tau2tau protein |
9354PRDX3peroxiredoxin 31thioredoxin dependent peroxide reductase |
11506SYPsynaptophysin1synaptophysin |
11180SOD2superoxide dismutase 2, mitochondrial1SOD2 |
9352PRDX1peroxiredoxin 11Prx1 |
4827HBBhemoglobin, beta1hemoglobin |
17169PRDX4peroxiredoxin 41thioredoxin peroxidase |
4623GSRglutathione reductase1glutathione reductase |

 

Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9developed both an antioxidant system containing superoxide dismutase 1 (SOD1) SOD1 and a redox system including peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase
9353PRDX2peroxiredoxin 2Prx23.91 (SOD1) SOD1 and a redox system including peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase and glutathione peroxidase1 (GPx1): GPx1 SOD1 converts superoxide
4553GPX1glutathione peroxidase 1GPx12.2including peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase and glutathione peroxidase1 (GPx1): GPx1 SOD1 converts superoxide radicals into hydrogen peroxide (H H 2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9peroxiredoxin2 (Prx2, Prx2 thioredoxin peroxidase and glutathione peroxidase1 (GPx1): GPx1 SOD1 converts superoxide radicals into hydrogen peroxide (H H 2 O
9353PRDX2peroxiredoxin 2Prx23.9(H H 2 O and oxygen (O O 2 by Prx2 and GPx1 that directly regulate the redox system
4553GPX1glutathione peroxidase 1GPx12.22 O and oxygen (O O 2 by Prx2 and GPx1 that directly regulate the redox system
9353PRDX2peroxiredoxin 2Prx23.9biological significance of the interaction of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we
4553GPX1glutathione peroxidase 1GPx12.2significance of the interaction of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we produced
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the interaction of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we produced an affinity-purified
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7of the redox system (Prx2/GPx1) Prx2 GPx1 with SOD1 in SOD1-mutated motor neurons in vivo we produced an affinity-purified rabbit antibody
9353PRDX2peroxiredoxin 2Prx23.9neurons in vivo we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in
9353PRDX2peroxiredoxin 2Prx23.9rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) LBHIs
4553GPX1glutathione peroxidase 1GPx12.2against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) LBHIs in the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9and an Ala Val substitution at codon 4 in the SOD1 gene as well as in transgenic rats expressing human SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9SOD1 gene as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2
9353PRDX2peroxiredoxin 2Prx23.9SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1 the reaction product deposits with the antibodies against
4553GPX1glutathione peroxidase 1GPx12.2patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1 the reaction product deposits with the antibodies against Prx2 and
9353PRDX2peroxiredoxin 2Prx23.9and GPx1 the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs
4553GPX1glutathione peroxidase 1GPx12.2the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9In addition the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 Prx2 GPx1 were similar in the inclusions the
9353PRDX2peroxiredoxin 2Prx23.9addition the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 Prx2 GPx1 were similar in the inclusions the co-aggregation of Prx2/GPx1
4553GPX1glutathione peroxidase 1GPx12.2the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 Prx2 GPx1 were similar in the inclusions the co-aggregation of Prx2/GPx1 Prx2
9353PRDX2peroxiredoxin 2Prx23.9GPx1 were similar in the inclusions the co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS
4553GPX1glutathione peroxidase 1GPx12.2were similar in the inclusions the co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9in the inclusions the co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-related1.7Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident
9353PRDX2peroxiredoxin 2Prx23.9Based on the fact that Prx2/GPx1 Prx2 GPx1 directly regulates the redox system such co-aggregation of Prx2/GPx1
4553GPX1glutathione peroxidase 1GPx12.2Based on the fact that Prx2/GPx1 Prx2 GPx1 directly regulates the redox system such co-aggregation of Prx2/GPx1 Prx2
9353PRDX2peroxiredoxin 2Prx23.9GPx1 directly regulates the redox system such co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs may lead to the
4553GPX1glutathione peroxidase 1GPx12.2directly regulates the redox system such co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the redox system such co-aggregation of Prx2/GPx1 Prx2 GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mediated1.7breakdown of the redox system itself thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-linked1.7system itself thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1.7first antioxidant enzyme group three isoforms of superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9of superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
11180SOD2superoxide dismutase 2, mitochondrialSOD20.9superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
11181SOD3superoxide dismutase 3, extracellularSOD30.9superoxide dismutase (SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
11181SOD3superoxide dismutase 3, extracellularSOD30.9(SOD) SOD EC 1.15.1.1 have been identified SOD1 SOD2 and SOD3 9
16753PRDX6peroxiredoxin 6Prx0.3In the second enzyme group the peroxiredoxin (Prx) Prx and glutathione peroxidase (GPx) GPx families as well as catalase
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1.7Unlike SOD and catalase enzymes of the Prx and GPx families require
16753PRDX6peroxiredoxin 6Prx0.3Unlike SOD and catalase enzymes of the Prx and GPx families require secondary enzymes and cofactors to function
9353PRDX2peroxiredoxin 2Prx23.9Peroxiredoxin2 (Prx2) Prx2 is a novel organ-specific antioxidative enzyme that is mainly expressed
16753PRDX6peroxiredoxin 6Prx0.3This protein is a member of Prx family whose members possess reactive cysteine residues 23
9353PRDX2peroxiredoxin 2Prx23.9Prx2 requires thioredoxin reductase (TR) TR as a secondary enzyme as
9353PRDX2peroxiredoxin 2Prx23.9as cofactors to function at high efficiency the activity of Prx2 in the thioredoxin/TR/NADPH thioredoxin TR NADPH system is over five
9353PRDX2peroxiredoxin 2Prx23.9NADPH system is over five times higher than that of Prx2 by itself 5
9353PRDX2peroxiredoxin 2Prx23.9In this milieu Prx2 is also called thioredoxin peroxidase 1 (thioredoxin-dependent thioredoxin-dependent peroxide reductase
9353PRDX2peroxiredoxin 2Prx23.9to controlling the intracellular content of H 2 O 2 Prx2 directly regulates the redox signals of the thioredoxin/TR/NADPH thioredoxin TR
4553GPX1glutathione peroxidase 1GPx12.2EC 1.11.1.9 a classical selenium-dependent isoform (also also assigned as GPx1 was first described as an enzyme that protects hemoglobin from
4827HBBhemoglobin, betahemoglobin1.0as GPx1 was first described as an enzyme that protects hemoglobin from oxidative degradation in red blood cells 25
4553GPX1glutathione peroxidase 1GPx12.2Among them GPx1 is considered as the major enzyme responsible for removing intracytoplasmic
9353PRDX2peroxiredoxin 2Prx23.9Like Prx2 GPx1 needs glutathione reductase (GR) GR as a secondary enzyme
4553GPX1glutathione peroxidase 1GPx12.2Like Prx2 GPx1 needs glutathione reductase (GR) GR as a secondary enzyme as
9353PRDX2peroxiredoxin 2Prx23.9Therefore Prx2 and GPx1 directly control the redox system
4553GPX1glutathione peroxidase 1GPx12.2Therefore Prx2 and GPx1 directly control the redox system
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9amyotrophic lateral sclerosis (FALS) FALS are caused by a mutant SOD1 15 17 18
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9SOD1 is thought to be an essential component of neuronal Lewy
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7LBHIs in affected anterior horn cells are morphological hallmarks of SOD1-mutated motor neurons of FALS patients 3 11 12 13 14
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7To cope with destructive ROSs even SOD1-mutated motor neurons induce mutant and wild-type SOD1 as well as
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9destructive ROSs even SOD1-mutated motor neurons induce mutant and wild-type SOD1 as well as Prx2 and GPx1
9353PRDX2peroxiredoxin 2Prx23.9motor neurons induce mutant and wild-type SOD1 as well as Prx2 and GPx1
4553GPX1glutathione peroxidase 1GPx12.2induce mutant and wild-type SOD1 as well as Prx2 and GPx1
9353PRDX2peroxiredoxin 2Prx23.9Considering that Prx2 and GPx1 interact not only with wild-type SOD1 but also
4553GPX1glutathione peroxidase 1GPx12.2Considering that Prx2 and GPx1 interact not only with wild-type SOD1 but also with mutant
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Considering that Prx2 and GPx1 interact not only with wild-type SOD1 but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9interact not only with wild-type SOD1 but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been
9353PRDX2peroxiredoxin 2Prx23.9SOD1 but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been suggested to contribute to mutant
4553GPX1glutathione peroxidase 1GPx12.2but also with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been suggested to contribute to mutant SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9with mutant SOD1 the interaction of Prx2/GPx1 Prx2 GPx1 with SOD1 has been suggested to contribute to mutant SOD1 aggregation toxicity
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9GPx1 with SOD1 has been suggested to contribute to mutant SOD1 aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in
9353PRDX2peroxiredoxin 2Prx23.9been suggested to contribute to mutant SOD1 aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in SOD1-mutated motor neurons
4553GPX1glutathione peroxidase 1GPx12.2suggested to contribute to mutant SOD1 aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in SOD1-mutated motor neurons
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7aggregation toxicity Prx2/GPx1 Prx2 GPx1 possibly aggregate as LBHIs in SOD1-mutated motor neurons
9353PRDX2peroxiredoxin 2Prx23.9Furthermore the aggregation of Prx2/GPx1 Prx2 GPx1 might affect the intracytoplasmic redox regulation and amplify mutant
4553GPX1glutathione peroxidase 1GPx12.2Furthermore the aggregation of Prx2/GPx1 Prx2 GPx1 might affect the intracytoplasmic redox regulation and amplify mutant SOD1-mediated
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mediated1.7GPx1 might affect the intracytoplasmic redox regulation and amplify mutant SOD1-mediated toxicity
9353PRDX2peroxiredoxin 2Prx23.9To clarify the biological significance of the interaction of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons
4553GPX1glutathione peroxidase 1GPx12.2clarify the biological significance of the interaction of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons in
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the interaction of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons in vivo we first produced an
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7of Prx2/GPx1 Prx2 GPx1 (redox redox system with SOD1 in SOD1-mutated motor neurons in vivo we first produced an antibody against
9353PRDX2peroxiredoxin 2Prx23.9motor neurons in vivo we first produced an antibody against Prx2 and analyzed the characteristic expressions of both Prx2 and GPx1
9353PRDX2peroxiredoxin 2Prx23.9antibody against Prx2 and analyzed the characteristic expressions of both Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated motor neurons of
4553GPX1glutathione peroxidase 1GPx12.2Prx2 and analyzed the characteristic expressions of both Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated motor neurons of humans and
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7expressions of both Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated motor neurons of humans and animal models
9353PRDX2peroxiredoxin 2Prx23.9Preparation of polyclonal antibody against Prx2 A synthetic peptide corresponding to the C-terminal region of Prx2
9353PRDX2peroxiredoxin 2Prx23.9Prx2 A synthetic peptide corresponding to the C-terminal region of Prx2 (amino amino acids 184_amp_#x2013 198 NH 2 -KPNVDDSKEYFSKHN-COOH with or
9353PRDX2peroxiredoxin 2Prx23.9of the C-terminal region of the human rat or mouse Prx2
9353PRDX2peroxiredoxin 2Prx23.9To prepare immunogen 6 mg synthesized Prx2 peptide was conjugated with 6 mg keyhole limpet hemocyanin (KLH)
9353PRDX2peroxiredoxin 2Prx23.9an affinity column of immobilized KLH conjugated with the synthetic Prx2 peptide as described previously 16
9353PRDX2peroxiredoxin 2Prx23.9Fig 1 Specificity of antibody against Prx2
9353PRDX2peroxiredoxin 2Prx23.9The immunoreactivity of the antibody to HSA-conjugated Prx2 peptide ( solid circles and native HSA ( open circles
9353PRDX2peroxiredoxin 2Prx23.9The anti-Prx2 antibody recognizes the HSA-conjugated Prx2 peptide but does not react with HAS ( Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9HSA-conjugated Prx2 peptide but does not react with HAS ( Prx2 peroxiredoxin2 ELISA enzyme-linked immunosorbent assay HAS human serum albumin
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9SOD1 analysis revealed that the members of the Japanese Oki family
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1.7of five FALS cases ( FALS familial amyotrophic lateral sclerosis SOD superoxide dismutase LBHI Lewy body-like hyaline inclusion 2-bp two-base pair
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9transgenic line (H46R-4) H46R-4 in which the level of human SOD1 with the H46R mutation was 6 times the level of
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9was 6 times the level of that of endogenous rat SOD1 27
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9transgenic line (G93A-39) G93A-39 in which the level of human SOD1 with the G93A mutation was 2.5 times the level of
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9G93A mutation was 2.5 times the level of endogenous rat SOD1 27
9353PRDX2peroxiredoxin 2Prx23.9following primary antibodies were utilized an affinity-purified rabbit antibody against Prx2 (concentration: concentration 1 _amp_micro;g/ml), _amp_micro g ml a polyclonal antibody
4553GPX1glutathione peroxidase 1GPx12.2concentration 1 _amp_micro;g/ml), _amp_micro g ml a polyclonal antibody to GPx1 diluted 1 2 000 in 1% bovine serum albumin-containing phosphate-buffered
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9BSA-PBS pH 7.4 2 and a polyclonal antibody to human SOD1 (diluted diluted 1 10 000 in 1% BSA-PBS pH 7.4
9353PRDX2peroxiredoxin 2Prx23.9had been preabsorbed with an excess amount of the synthetic Prx2 peptide
9353PRDX2peroxiredoxin 2Prx23.9Results We successfully produced an affinity-purified rabbit antibody against Prx2 peptide (amino amino acids 184_amp_#x2013 198 although this amino acid
9353PRDX2peroxiredoxin 2Prx23.9of the human rat mouse Chinese hamster or Bos Taurus Prx2 this peptide does not share homology with other members of
16753PRDX6peroxiredoxin 6Prx0.3peptide does not share homology with other members of the Prx family or any other peptide sequence in GenomeNet and applied
9353PRDX2peroxiredoxin 2Prx23.9This anti-Prx2 antibody recognized the HSA-conjugated Prx2 peptide but did not react with HSA (Fig Fig 1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-linked1.7In mutant SOD1-linked FALS patients the neuronal LBHIs were generally composed of eosinophilic
9353PRDX2peroxiredoxin 2Prx23.9Prx2 immunoreactivity in normal spinal cords was identified in almost all
9353PRDX2peroxiredoxin 2Prx2-immunostaining3.3In addition Prx2-immunostaining was found throughout the neuropil with considerably lower intensity (Fig
9353PRDX2peroxiredoxin 2Prx23.9With respect to the intracellular localization of Prx2 immunostaining of the neuronal cytoplasm and proximal dendrites was specifically
9353PRDX2peroxiredoxin 2Prx23.9that had been pretreated with an excess of the synthetic Prx2 produced no staining (Fig Fig 3 D
4553GPX1glutathione peroxidase 1GPx12.2B C Immunostaining for GPx1 ( B and Prx2 ( C
9353PRDX2peroxiredoxin 2Prx23.9B C Immunostaining for GPx1 ( B and Prx2 ( C
4553GPX1glutathione peroxidase 1GPx12.2GPx1 and Prx2 immunoreactivities are found diffusely in the neuropil with
9353PRDX2peroxiredoxin 2Prx23.9GPx1 and Prx2 immunoreactivities are found diffusely in the neuropil with considerably less
4553GPX1glutathione peroxidase 1GPx12.2No counterstaining ( HE hematoxylin and eosin GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9No counterstaining ( HE hematoxylin and eosin GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9Fig 3 Detection of Prx2 and GPx1 in the normal motor neurons of the human
4553GPX1glutathione peroxidase 1GPx12.2Fig 3 Detection of Prx2 and GPx1 in the normal motor neurons of the human spinal cord
4553GPX1glutathione peroxidase 1GPx12.2B Immunostaining with the antibody against GPx1 showing GPx1-positive neurons
4553GPX1glutathione peroxidase 1GPx1-positive1.9B Immunostaining with the antibody against GPx1 showing GPx1-positive neurons
9353PRDX2peroxiredoxin 2Prx23.9C Immunostaining with the antibody to Prx2
4553GPX1glutathione peroxidase 1GPx12.2the normal motor neurons in the spinal cord co-express both GPx1 ( B and Prx2 ( C although their staining intensities
9353PRDX2peroxiredoxin 2Prx23.9in the spinal cord co-express both GPx1 ( B and Prx2 ( C although their staining intensities in neurons vary
9353PRDX2peroxiredoxin 2Prx23.9with anti-Prx2 antibody pretreated with an excess of the synthetic Prx2 peptide
4553GPX1glutathione peroxidase 1GPx12.2E GPx1 immunostaining of the neuronal cytoplasm and proximal dendrites is observed
9353PRDX2peroxiredoxin 2Prx23.9F Prx2 immunostaining of the neuronal cytoplasm and proximal dendrites is observed
4553GPX1glutathione peroxidase 1GPx12.2B _amp_#x2013 F No counterstaining ( HE hematoxylin and eosin GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9No counterstaining ( HE hematoxylin and eosin GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9_amp_micro m A neuropil staining pattern similar to that for Prx2 was observed with GPx1 weak GPx1 immunoreactivity was diffusely seen
4553GPX1glutathione peroxidase 1GPx12.2staining pattern similar to that for Prx2 was observed with GPx1 weak GPx1 immunoreactivity was diffusely seen in the neuropil in
4553GPX1glutathione peroxidase 1GPx12.2similar to that for Prx2 was observed with GPx1 weak GPx1 immunoreactivity was diffusely seen in the neuropil in transverse sections
4553GPX1glutathione peroxidase 1GPx12.2GPx1 immunostaining was observed in the cytoplasm with cell bodies and
9353PRDX2peroxiredoxin 2Prx23.9The stainability and intensity of Prx2 and GPx1 in the normal anterior horn cells of the
4553GPX1glutathione peroxidase 1GPx12.2The stainability and intensity of Prx2 and GPx1 in the normal anterior horn cells of the spinal cords
9353PRDX2peroxiredoxin 2Prx23.9the normal motor neurons in the spinal cords co-expressed both Prx2 and GPx1 (Fig Fig 3 A_amp_#x2013 C although the staining
4553GPX1glutathione peroxidase 1GPx12.2motor neurons in the spinal cords co-expressed both Prx2 and GPx1 (Fig Fig 3 A_amp_#x2013 C although the staining intensities of
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9C family and the transgenic rats expressing two different human SOD1 mutations (H46R H46R and G93A were intensely immunostained by the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9and G93A were intensely immunostained by the antibody against human SOD1 (Figs Figs 4 A D 5 A D 6 A
9353PRDX2peroxiredoxin 2Prx23.9Most neuronal LBHIs were also immunoreactive for Prx2 although the intensity of Prx2 immunoreactivity in the LBHIs varied
9353PRDX2peroxiredoxin 2Prx23.9LBHIs were also immunoreactive for Prx2 although the intensity of Prx2 immunoreactivity in the LBHIs varied (Figs Figs 4 C F
9353PRDX2peroxiredoxin 2Prx23.9rats (H46R H46R and G93A showed a similar immunoreactivity for Prx2
9353PRDX2peroxiredoxin 2Prx23.9The Prx2 immunolocalization in many intracytoplasmic and intraneuritic LBHIs was similar to
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9many intracytoplasmic and intraneuritic LBHIs was similar to that of SOD1 in both diseases
9353PRDX2peroxiredoxin 2Prx23.9halo-type LBHIs the reaction product deposits of the antibody against Prx2 were generally restricted to the periphery (Fig Fig 4 C
9353PRDX2peroxiredoxin 2Prx23.9In ill-defined LBHIs Prx2 immunostaining was distributed throughout each inclusion
9353PRDX2peroxiredoxin 2Prx23.9In some inclusions however expression of Prx2 was observed in only part of the inclusion (Fig Fig
4553GPX1glutathione peroxidase 1GPx12.2With respect to the GPx1 immunostaining in the neuronal LBHIs similar stainability and immunolocalization to
9353PRDX2peroxiredoxin 2Prx23.9immunostaining in the neuronal LBHIs similar stainability and immunolocalization to Prx2 were confirmed in the core and halo types as well
4553GPX1glutathione peroxidase 1GPx12.2The immunoreactivity for GPx1 in the FALS patients was similar to that in the
9353PRDX2peroxiredoxin 2Prx23.9Like Prx2 the immunolocalization of GPx1 was similar to that of SOD1
4553GPX1glutathione peroxidase 1GPx12.2Like Prx2 the immunolocalization of GPx1 was similar to that of SOD1 in both diseases
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Prx2 the immunolocalization of GPx1 was similar to that of SOD1 in both diseases
4553GPX1glutathione peroxidase 1GPx1-immunoreactive1.9GPx1-immunoreactive products in many core and halo-type inclusions were mainly localized
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9an FALS patient with a two-base pair deletion in the SOD1 gene
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9A Immunostaining for SOD1 immunoreactivity is mostly restricted to the halo
4553GPX1glutathione peroxidase 1GPx12.2B Immunostaining for GPx1 immunoreactivity is located in the SOD1-positive portion of the LBHI
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-positive1.7B Immunostaining for GPx1 immunoreactivity is located in the SOD1-positive portion of the LBHI
9353PRDX2peroxiredoxin 2Prx23.9C Immunoreactivity for Prx2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Co-localization of the three proteins SOD1 GPx1 and Prx2 in the LBHI is evident
4553GPX1glutathione peroxidase 1GPx12.2Co-localization of the three proteins SOD1 GPx1 and Prx2 in the LBHI is evident
9353PRDX2peroxiredoxin 2Prx23.9Co-localization of the three proteins SOD1 GPx1 and Prx2 in the LBHI is evident
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9core and halo-type LBHI in a transgenic rat expressing human SOD1 with an H46R mutation
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
4553GPX1glutathione peroxidase 1GPx12.2Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
9353PRDX2peroxiredoxin 2Prx23.9Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Similar stainability and immunolocalization of SOD1 GPx1 and Prx2 in the LBHI are observed ( LBHI
4553GPX1glutathione peroxidase 1GPx12.2Similar stainability and immunolocalization of SOD1 GPx1 and Prx2 in the LBHI are observed ( LBHI Lewy
9353PRDX2peroxiredoxin 2Prx23.9Similar stainability and immunolocalization of SOD1 GPx1 and Prx2 in the LBHI are observed ( LBHI Lewy body-like hyaline
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9LBHI Lewy body-like hyaline inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
4553GPX1glutathione peroxidase 1GPx12.2inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9LBHI in an FALS patient with an A4V mutation in SOD1 gene
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Immunostaining for SOD1 ( A GPx1 ( B and Prx2 ( C
4553GPX1glutathione peroxidase 1GPx12.2Immunostaining for SOD1 ( A GPx1 ( B and Prx2 ( C
9353PRDX2peroxiredoxin 2Prx23.9Immunostaining for SOD1 ( A GPx1 ( B and Prx2 ( C
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9an FALS patient with a two-base pair deletion in the SOD1 gene
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
4553GPX1glutathione peroxidase 1GPx12.2Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
9353PRDX2peroxiredoxin 2Prx23.9Immunostaining for SOD1 ( D GPx1 ( E and Prx2 ( F
4553GPX1glutathione peroxidase 1GPx12.2Immunostaining GPx1 ( E and Prx2 ( F are observed in only
9353PRDX2peroxiredoxin 2Prx23.9Immunostaining GPx1 ( E and Prx2 ( F are observed in only part of the SOD1-positive
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-positive1.7Prx2 ( F are observed in only part of the SOD1-positive LBHI
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9LBHI Lewy body-like hyaline inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
4553GPX1glutathione peroxidase 1GPx12.2inclusion FALS familial amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9amyotrophic lateral sclerosis SOD1 superoxide dismutase 1 GPx1 glutathione peroxidase1 Prx2 peroxiredoxin2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the spinal anterior horn in a transgenic rat expressing human SOD1 with an H46R mutation immunostained with antibodies against SOD1 (
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9human SOD1 with an H46R mutation immunostained with antibodies against SOD1 ( A and Prx2 ( B
9353PRDX2peroxiredoxin 2Prx23.9H46R mutation immunostained with antibodies against SOD1 ( A and Prx2 ( B
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9and sausage-like LBHIs in the neuropil are positive for both SOD1 and Prx2 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy
9353PRDX2peroxiredoxin 2Prx23.9LBHIs in the neuropil are positive for both SOD1 and Prx2 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9are positive for both SOD1 and Prx2 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion Prx2 peroxiredoxin2
9353PRDX2peroxiredoxin 2Prx23.9arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion Prx2 peroxiredoxin2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the spinal anterior horn in a transgenic rat expressing human SOD1 with an H46R mutation immunostained with antibodies against SOD1 (
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9human SOD1 with an H46R mutation immunostained with antibodies against SOD1 ( A and GPx1 ( B
4553GPX1glutathione peroxidase 1GPx12.2H46R mutation immunostained with antibodies against SOD1 ( A and GPx1 ( B
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Round LBHIs in the neuropil are positive for both SOD1 and GPx1 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy
4553GPX1glutathione peroxidase 1GPx12.2LBHIs in the neuropil are positive for both SOD1 and GPx1 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9are positive for both SOD1 and GPx1 ( arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion GPx1 glutathione peroxidase1
4553GPX1glutathione peroxidase 1GPx12.2arrows ( SOD1 superoxide dismutase1 LBHI Lewy body-like hyaline inclusion GPx1 glutathione peroxidase1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.950 _amp_micro m Noticeably the co-localization of the three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients
9353PRDX2peroxiredoxin 2Prx23.9_amp_micro m Noticeably the co-localization of the three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients and
4553GPX1glutathione peroxidase 1GPx12.2Noticeably the co-localization of the three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients and transgenic rats
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7three proteins SOD1 Prx2 and GPx1 in neuronal LBHIs in SOD1-mutated FALS patients and transgenic rats (H46R H46R and G93A was
9353PRDX2peroxiredoxin 2Prx23.9LBHIs the precise intra-inclusional immunolocalizations of the three proteins differed Prx2 (Fig Fig 5 D F and GPx1 (Fig Fig 5
4553GPX1glutathione peroxidase 1GPx12.2three proteins differed Prx2 (Fig Fig 5 D F and GPx1 (Fig Fig 5 D E immunostaining was observed in only
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-positive1.7E immunostaining was observed in only some areas of the SOD1-positive LBHIs
9353PRDX2peroxiredoxin 2Prx23.9Discussion Under normal physiological conditions Prx2 and GPx1 immunoreactivities in the spinal cord anterior horns in
4553GPX1glutathione peroxidase 1GPx12.2Discussion Under normal physiological conditions Prx2 and GPx1 immunoreactivities in the spinal cord anterior horns in humans and
9352PRDX1peroxiredoxin 1Prx11.3Like Prx1 26 33 intranuclear localization in some neurons is also observed
9353PRDX2peroxiredoxin 2Prx23.933 intranuclear localization in some neurons is also observed in Prx2 immunostaining
9353PRDX2peroxiredoxin 2Prx23.9Considering that endogenous Prx2 and GPx1 within the neuronal cytoplasm are extremely effective regulators
4553GPX1glutathione peroxidase 1GPx12.2Considering that endogenous Prx2 and GPx1 within the neuronal cytoplasm are extremely effective regulators of the
9353PRDX2peroxiredoxin 2Prx23.9almost all of the normal spinal motor neurons co-expressed both Prx2 and GPx1 confirms that these motor neurons maintain themselves using
4553GPX1glutathione peroxidase 1GPx12.2of the normal spinal motor neurons co-expressed both Prx2 and GPx1 confirms that these motor neurons maintain themselves using the intracellular
9353PRDX2peroxiredoxin 2Prx23.9that these motor neurons maintain themselves using the intracellular Prx2/GPx1 Prx2 GPx1 system that is the redox system
4553GPX1glutathione peroxidase 1GPx12.2these motor neurons maintain themselves using the intracellular Prx2/GPx1 Prx2 GPx1 system that is the redox system
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9As expected 12 13 16 27 30 SOD1 protein (probably probably the mutant form was found to aggregate
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9anterior horn cells as neuronal LBHIs in FALS patients with SOD1 gene mutations and transgenic rats expressing human SOD1 with H46R
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9patients with SOD1 gene mutations and transgenic rats expressing human SOD1 with H46R and G93A mutations
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Intense co-expression of SOD1 Prx2 and GPx1 in neuronal LBHIs in both diseases was
9353PRDX2peroxiredoxin 2Prx23.9Intense co-expression of SOD1 Prx2 and GPx1 in neuronal LBHIs in both diseases was evident
4553GPX1glutathione peroxidase 1GPx12.2Intense co-expression of SOD1 Prx2 and GPx1 in neuronal LBHIs in both diseases was evident
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7To eliminate ROSs SOD1-mutated motor neurons in mutant SOD1-linked FALS and transgenic rats (G46R
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-linked1.7To eliminate ROSs SOD1-mutated motor neurons in mutant SOD1-linked FALS and transgenic rats (G46R G46R and G93A induce mutant/wild-type
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9transgenic rats (G46R G46R and G93A induce mutant/wild-type mutant wild-type SOD1 as an antioxidant system and Prx2/GPx1 Prx2 GPx1 as a
9353PRDX2peroxiredoxin 2Prx23.9mutant/wild-type mutant wild-type SOD1 as an antioxidant system and Prx2/GPx1 Prx2 GPx1 as a redox system
4553GPX1glutathione peroxidase 1GPx12.2mutant wild-type SOD1 as an antioxidant system and Prx2/GPx1 Prx2 GPx1 as a redox system
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9In this in vivo milieu where mutant SOD1 exists Prx2 and GPx1 would aberrantly interact with the mutant
9353PRDX2peroxiredoxin 2Prx23.9In this in vivo milieu where mutant SOD1 exists Prx2 and GPx1 would aberrantly interact with the mutant SOD1 which
4553GPX1glutathione peroxidase 1GPx12.2this in vivo milieu where mutant SOD1 exists Prx2 and GPx1 would aberrantly interact with the mutant SOD1 which is assumed
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9exists Prx2 and GPx1 would aberrantly interact with the mutant SOD1 which is assumed to aggregate easily by itself 8
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Among the multiple theories of how mutant SOD1 contributes to motor neuron death in mutant SOD1-related FALS and
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-related1.7how mutant SOD1 contributes to motor neuron death in mutant SOD1-related FALS and transgenic animal models expressing human mutant SOD1 the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9mutant SOD1-related FALS and transgenic animal models expressing human mutant SOD1 the aggregation of mutant SOD1 in neurons leads to part
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9animal models expressing human mutant SOD1 the aggregation of mutant SOD1 in neurons leads to part of the mutant SOD1-mediated toxicity
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mediated1.7mutant SOD1 in neurons leads to part of the mutant SOD1-mediated toxicity through the formation of advanced glycation endproduct-modified SOD1 that
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9mutant SOD1-mediated toxicity through the formation of advanced glycation endproduct-modified SOD1 that is insoluble and cytotoxic 16
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9with a two-base pair deletion at codon 126 of the SOD1 gene (Oki Oki family and G85R transgenic mice has revealed
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9G85R transgenic mice has revealed that not only does mutant SOD1 provoke inclusion formation but that normal SOD1 also co-aggregates in
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9only does mutant SOD1 provoke inclusion formation but that normal SOD1 also co-aggregates in these inclusions 3
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9with the facts that there are neuronal LBHIs positive for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists
9353PRDX2peroxiredoxin 2Prx23.9the facts that there are neuronal LBHIs positive for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists but
4553GPX1glutathione peroxidase 1GPx12.2that there are neuronal LBHIs positive for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists but no LBHIs
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9for SOD1 Prx2 and GPx1 in the milieu where mutant SOD1 exists but no LBHIs (no no aggregations exist under physiological
9353PRDX2peroxiredoxin 2Prx23.9physiological conditions our study demonstrates an aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 the aggregation of which results in
4553GPX1glutathione peroxidase 1GPx12.2conditions our study demonstrates an aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 the aggregation of which results in neuronal
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9demonstrates an aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 the aggregation of which results in neuronal LBHIs
9353PRDX2peroxiredoxin 2Prx23.9In addition intra-inclusional co-aggregation of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1,
4553GPX1glutathione peroxidase 1GPx12.2In addition intra-inclusional co-aggregation of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1, Prx2
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9In addition intra-inclusional co-aggregation of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1, Prx2 GPx1 thereby reducing
9353PRDX2peroxiredoxin 2Prx23.9GPx1 with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1, Prx2 GPx1 thereby reducing the availability of the redox system
4553GPX1glutathione peroxidase 1GPx12.2with mutant SOD1 causes the intracytoplasmic reduction of Prx2/GPx1, Prx2 GPx1 thereby reducing the availability of the redox system
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1.7A similar aberrant interaction of the copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs
1613CCScopper chaperone for superoxide dismutaseCCS1.2similar aberrant interaction of the copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9interaction of the copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the formation of
1613CCScopper chaperone for superoxide dismutaseCCS-mutant1.2copper chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the formation of the neuronal LBHIs
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9chaperone for SOD (CCS) CCS and SOD1 (probably probably CCS-mutant SOD1 also occurs in the formation of the neuronal LBHIs in
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-linked1.7occurs in the formation of the neuronal LBHIs in mutant SOD1-linked FALS 19 and the mutant SOD1 transgenic mouse model 32
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9neuronal LBHIs in mutant SOD1-linked FALS 19 and the mutant SOD1 transgenic mouse model 32
6893MAPTmicrotubule-associated protein tautau0.8been observed for normal cytosolic constitutive proteins including tubulin and tau protein as well as neuron-specific constitutive proteins containing phosphorylated neurofilament
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9normal constitutive proteins with the aberrant interaction of cytotoxic mutant SOD1 with Prx2/GPx1 Prx2 GPx1 directly regulating a redox system our
9353PRDX2peroxiredoxin 2Prx23.9with the aberrant interaction of cytotoxic mutant SOD1 with Prx2/GPx1 Prx2 GPx1 directly regulating a redox system our finding leads us
4553GPX1glutathione peroxidase 1GPx12.2the aberrant interaction of cytotoxic mutant SOD1 with Prx2/GPx1 Prx2 GPx1 directly regulating a redox system our finding leads us to
9353PRDX2peroxiredoxin 2Prx23.9leads us to speculate that not only co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 into LBHIs but also intracytoplasmic reduction of
4553GPX1glutathione peroxidase 1GPx12.2us to speculate that not only co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 into LBHIs but also intracytoplasmic reduction of Prx2/GPx1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9speculate that not only co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 into LBHIs but also intracytoplasmic reduction of Prx2/GPx1 Prx2 GPx1
9353PRDX2peroxiredoxin 2Prx23.9and SOD1 into LBHIs but also intracytoplasmic reduction of Prx2/GPx1 Prx2 GPx1 in both diseases may partly contribute to the breakdown
4553GPX1glutathione peroxidase 1GPx12.2SOD1 into LBHIs but also intracytoplasmic reduction of Prx2/GPx1 Prx2 GPx1 in both diseases may partly contribute to the breakdown of
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7to the breakdown of the redox system itself in these SOD1-mutated neurons and this may be one of the endogenous mechanisms
9353PRDX2peroxiredoxin 2Prx23.9remains to be determined whether this aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 is a direct or an indirect
4553GPX1glutathione peroxidase 1GPx12.2to be determined whether this aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 is a direct or an indirect effect
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9whether this aberrant interaction of Prx2/GPx1 Prx2 GPx1 with mutant SOD1 is a direct or an indirect effect based on the
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mutated1.7direct or an indirect effect based on the pathogenesis of SOD1-mutated FALS disease itself or whether Prx2 and GPx1 play a
9353PRDX2peroxiredoxin 2Prx23.9on the pathogenesis of SOD1-mutated FALS disease itself or whether Prx2 and GPx1 play a primary or a secondary role to
4553GPX1glutathione peroxidase 1GPx12.2pathogenesis of SOD1-mutated FALS disease itself or whether Prx2 and GPx1 play a primary or a secondary role to mutant SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9GPx1 play a primary or a secondary role to mutant SOD1
9353PRDX2peroxiredoxin 2Prx23.9to emphasize that the aberrant interaction and co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant
4553GPX1glutathione peroxidase 1GPx12.2emphasize that the aberrant interaction and co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9the aberrant interaction and co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS
9353PRDX2peroxiredoxin 2Prx23.9co-aggregation of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene
4553GPX1glutathione peroxidase 1GPx12.2of Prx2/GPx1 Prx2 GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene mutations
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9GPx1 and SOD1 (probably probably Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene mutations and transgenic rats
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9Prx2/GPx1 Prx2 GPx1 and mutant SOD1 in FALS patients with SOD1 gene mutations and transgenic rats expressing human SOD1 mutations may
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD17.9patients with SOD1 gene mutations and transgenic rats expressing human SOD1 mutations may amplify a more marked mutant SOD1-mediated toxicity
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))SOD1-mediated1.7expressing human SOD1 mutations may amplify a more marked mutant SOD1-mediated toxicity
9353PRDX2peroxiredoxin 2peroxiredoxin21.0to protect themselves from these ross the cells have developed both an antioxidant system containing superoxide dismutase 1 sod1 and a redox system including peroxiredoxin2 prx2 thioredoxin peroxidase and glutathione peroxidase1 gpx1 : sod1 converts superoxide radicals into hydrogen peroxide h 2 o 2 and h 2 o 2 is then converted into harmless water h 2 o and oxygen o 2
17169PRDX4peroxiredoxin 4thioredoxin peroxidase1.0to protect themselves from these ross the cells have developed both an antioxidant system containing superoxide dismutase 1 sod1 and a redox system including peroxiredoxin2 prx2 thioredoxin peroxidase and glutathione peroxidase1 gpx1 : sod1 converts superoxide radicals into hydrogen peroxide h 2 o 2 and h 2 o 2 is then converted into harmless water h 2 o and oxygen o 2 by prx2 and gpx1 that direct
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0otect themselves from these ross the cells have developed both an antioxidant system containing superoxide dismutase 1 sod1 and a redox system including peroxiredoxin2 prx2 thioredoxin peroxidase and glutathione peroxidase1 gpx1 : sod1 converts superoxide radicals into hydrogen peroxide h 2 o 2 and h 2 o 2 is then converted into harmless water h 2 o and oxygen o 2 by prx2 and gpx1 that directly regulate the redox system
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase 11.0to protect themselves from these ross the cells have developed both an antioxidant system containing superoxide dismutase 1 sod1 and a redox system including peroxiredoxin2 prx2 thioredoxin peroxidase and glutathione peroxidase1 gpx1 : sod1 converts superoxide radicals into hydrogen peroxide h 2 o 2 and h 2 o 2 is then co
9353PRDX2peroxiredoxin 2peroxiredoxin 21.0keywords peroxiredoxin 2 glutathione peroxidase 1 redox system superoxide dismutase 1 familial amyotrophic lateral sclerosis
4553GPX1glutathione peroxidase 1glutathione peroxidase 11.0keywords peroxiredoxin 2 glutathione peroxidase 1 redox system superoxide dismutase 1 familial amyotrophic lateral sclerosis
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase 11.0keywords peroxiredoxin 2 glutathione peroxidase 1 redox system superoxide dismutase 1 familial amyotrophic lateral sclerosis
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0for the first antioxidant enzyme group three isoforms of superoxide dismutase sod [ec 1.15.1.1] have been identified: sod1 sod2 and sod3 [ 9 ].
1516CATcatalasecatalase1.0in the second enzyme group the peroxiredoxin prx and glutathione peroxidase gpx families as well as catalase localized within peroxisomes have been identified.
1516CATcatalasecatalase1.0unlike sod and catalase enzymes of the prx and gpx families require secondary enzymes and cofactors to function at high efficiency.
9353PRDX2peroxiredoxin 2peroxiredoxin21.0peroxiredoxin2 prx2 is a novel organ specific antioxidative enzyme that is mainly expressed in mammalian brain [ 23 ].
12435TXNthioredoxinthioredoxin1.0prx2 requires thioredoxin reductase tr as a secondary enzyme as well as thioredoxin and nadph as cofactors to function at high efficiency; the activity of prx2 in the thioredoxin/tr/nadph system is over five times higher than that of prx2 by itself [ 5 ].
9354PRDX3peroxiredoxin 3thioredoxin dependent peroxide reductase1.0in this milieu prx2 is also called thioredoxin peroxidase 1 thioredoxin dependent peroxide reductase 1 or thiol specific antioxidant [ 4 5 6 ].
9353PRDX2peroxiredoxin 2thioredoxin dependent peroxide reductase 11.0in this milieu prx2 is also called thioredoxin peroxidase 1 thioredoxin dependent peroxide reductase 1 or thiol specific antioxidant [ 4 5 6 ].
9353PRDX2peroxiredoxin 2thioredoxin peroxidase 11.0in this milieu prx2 is also called thioredoxin peroxidase 1 thioredoxin dependent peroxide reductase 1 or thiol specific antioxidant [ 4 5 6 ].
12435TXNthioredoxinthioredoxin1.0in addition to controlling the intracellular content of h 2 o 2 prx2 directly regulates the redox signals of the thioredoxin/tr/nadph system because alone the secondary enzyme and cofactors i.e. thioredoxin/tr/nadph can not directly regulate the redox system and can not act on h 2 o 2 .
4623GSRglutathione reductaseglutathione reductase1.0like prx2 gpx1 needs glutathione reductase gr as a secondary enzyme as well as glutathione and nadph as cofactors to work at high efficiency and this process is also one of the redox signals in living cells [ 21 24 ].
399ALBalbuminserum albumin1.0n of polyclonal antibody against prx2 a synthetic peptide corresponding to the c terminal region of prx2 amino acids 184_amp_#x2013;198: nh 2 kpnvddskeyfskhn cooh with or without conjugation to human serum albumin hsa at the carboxyl end was supplied by peptide institute osaka japan .
9353PRDX2peroxiredoxin 2peroxiredoxin21.0the anti prx2 antibody recognizes the hsa conjugated prx2 peptide but does not react with has prx2 peroxiredoxin2 elisa enzyme linked immunosorbent assay has human serum albumin
399ALBalbuminserum albumin1.0the anti prx2 antibody recognizes the hsa conjugated prx2 peptide but does not react with has prx2 peroxiredoxin2 elisa enzyme linked immunosorbent assay has human serum albumin
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase1.0table 1 characteristics of five fals cases fals familial amyotrophic lateral sclerosis sod superoxide dismutase lbhi lewy body like hyaline inclusion 2 bp two base pair pci posterior column involvement type + detected nd not determined as asphyxia ih intraperitoneal hemorrhage rd respiratory distress pn pneumo
399ALBalbuminserum albumin1.0the following primary antibodies were utilized: an affinity purified rabbit antibody against prx2 concentration: 1 _amp_micro;g/ml a polyclonal antibody to gpx1 [diluted 1:2 000 in 1% bovine serum albumin containing phosphate buffered saline bsa pbs ph 7.4] [ 2 ] and a polyclonal antibody to human sod1 diluted 1:10 000 in 1% bsa pbs ph 7.4 [ 1 ].
9353PRDX2peroxiredoxin 2peroxiredoxin21.0no counterstaining he hematoxylin and eosin gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0no counterstaining he hematoxylin and eosin gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
9353PRDX2peroxiredoxin 2peroxiredoxin21.0b _amp_#x2013; f no counterstaining he hematoxylin and eosin gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0b _amp_#x2013; f no counterstaining he hematoxylin and eosin gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
9353PRDX2peroxiredoxin 2peroxiredoxin21.0lization of sod1 gpx1 and prx2 in the lbhi are observed lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0r stainability and immunolocalization of sod1 gpx1 and prx2 in the lbhi are observed lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase 11.0similar stainability and immunolocalization of sod1 gpx1 and prx2 in the lbhi are observed lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
9353PRDX2peroxiredoxin 2peroxiredoxin21.0hese three proteins differ from each other in this lbhi lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0onal immunolocalizations of these three proteins differ from each other in this lbhi lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase 11.0the precise intra inclusional immunolocalizations of these three proteins differ from each other in this lbhi lbhi lewy body like hyaline inclusion fals familial amyotrophic lateral sclerosis sod1 superoxide dismutase 1 gpx1 glutathione peroxidase1 prx2 peroxiredoxin2 .
9353PRDX2peroxiredoxin 2peroxiredoxin21.0round and sausage like lbhis in the neuropil are positive for both sod1 and prx2 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion prx2 peroxiredoxin2 .
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase11.0round and sausage like lbhis in the neuropil are positive for both sod1 and prx2 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion prx2 peroxiredoxin2 .
4553GPX1glutathione peroxidase 1glutathione peroxidase11.0round lbhis in the neuropil are positive for both sod1 and gpx1 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion gpx1 glutathione peroxidase1 .
11179SOD1superoxide dismutase 1, soluble (amyotrophic lateral sclerosis 1 (adult))superoxide dismutase11.0round lbhis in the neuropil are positive for both sod1 and gpx1 arrows sod1 superoxide dismutase1 lbhi lewy body like hyaline inclusion gpx1 glutathione peroxidase1 .
11506SYPsynaptophysinsynaptophysin1.0or normal cytosolic constitutive proteins including tubulin and tau protein as well as neuron specific constitutive proteins containing phosphorylated neurofilament proteins nfp nonphosphorylated nfp synaptophysin and neuron specific enolase [ 13 17 18 ]; this results in partial impairment of the maintenance of cell metabolism [ 13 17 18 ].
6893MAPTmicrotubule-associated protein tautau protein1.0such sequestration into lbhis has also been observed for normal cytosolic constitutive proteins including tubulin and tau protein as well as neuron specific constitutive proteins containing phosphorylated neurofilament proteins nfp nonphosphorylated nfp synaptophysin and neuron specific enolase [ 13 17 18 ]; this results in par