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Validated All-in-One™ qPCR Primer for SOD1(NM_000454.4) Search again
Product ID:
HQP017615
(click here to view gene annotation page)
Powered by BiozSpecies:
Human
Symbol:
Alias:
ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP, hSod1, homodimer
Gene Description:
superoxide dismutase 1
Target Gene Accession:
NM_000454.4(click here to view gene page)
Estimated Delivery:
Approximately 1-3 weeks, but may vary. Please email sales@genecopoeia.com or call 301-762-0888 to confirm ETA.
Important Note:
By default, qPCR primer pairs are designed to measure the expression level of the splice variant (accession number) you selected for this gene WITHOUT consideration of other possible variants of this gene. If this gene has multiple variants, and you would like to measure the expression levels of one particular variant, multiple variants, or all variants, please contact us for a custom service project at inquiry@genecopoeia.com.
Validated result:
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| A | B |
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Each All-in-One™ qPCR Primer is experimentally validated to yield a single dissociation curve peak and to generate a single amplification of the correct size for the targeted gene. A cDNA Pool, containing reverse transcript products of 8 different human tissue total RNA(Liver, Testis,Muscle,Thyroid,Brain,Spleen,Stomach,Small Intestine)),was used as the qPCR validation template. qPCR was performed using 0.2 µM primer with 2XAll-in-One™ qPCR Mix (Catalog#: QP001,QP002,QP004,QP005). Reactions were incubated for 10min. at 95°C, followed by 40 cycles of 95°C for 10 sec.; 60°C, 20 sec. and 72°C, 15sec. using Bio-Rad iQ5™ Instrument. At the end of the last cycle, temperature was increased from 72 to 95°C to produce a melting curve. Panel A: Validated Result for Amplification Curve; Panel B: Validated Result for Melting Curve. |
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Summary
The protein encoded by this gene binds copper and zinc ions and is one of two isozymes responsible for destroying free superoxide radicals in the body. The encoded isozyme is a soluble cytoplasmic protein, acting as a homodimer to convert naturally-occuring but harmful superoxide radicals to molecular oxygen and hydrogen peroxide. The other isozyme is a mitochondrial protein. Mutations in this gene have been implicated as causes of familial amyotrophic lateral sclerosis. Rare transcript variants have been reported for this gene. [provided by RefSeq].
Gene References into function
- This study searched for the D90A CuZn-SOD mutation in different ethnic populations of the Russian Federation and found it in locations close to the Scandinavian peninsula and in remote populations in Asia, making this mutation the most common globally.
- Cu,Zn-SOD and Mn-SOD are differently regulated by estrogen and progesterone in human endometrial stromal cells
- Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome.
- mutant superoxide dismutases associated with familial amyotrophic lateral sclerosis
- 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis
- Transcriptional regulation and environmental induction of gene encoding copper- and zinc-containing superoxide dismutase.
- Homocysteine (HC) mediates oxidative cytotoxicity in cultured motor neurons by toxic gain of function of mutant SOD1 (A4V) indicating that motor neurons containing mutant SOD1 may be more susceptible to physiological concentrations of HC.
- Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: potential impact of CNTF as a candidate modifier gene.
- mutations of the gene have been linked to familial amyotrophic lateral sclerosis - review
- Identification of a novel mutation in Cu/Zn superoxide dismutase gene associated with familial amyotrophic lateral sclerosis. missense mutation (Ala140Gly) in exon 5
- causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice
- Effect of Cu,Zn superoxide dismutase on cholesterol metabolism in human hepatocarcinoma (HepG2) cells
- Transgenic mice expressing human SOD1 with ALS-linked mutations at 2 of the 4 His residues crucial for coordinated copper binding (H46R/H48Q develop motor neuron disease with fibrillar inclusions like mice with G37R, G58R, and G93A variants.
- causative genes for familial amyotrophic lateral sclerosis
- antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h middle cerebral artery occlusion
- SOD1 mutants are recognized by Dorfin protein and targeted for proteasomal degradation
- genetic heterogeneity of patients with ALS harboring mutations in the SOD1 gene
- The combination of Hsp70 abd Hsp40 reduced intracytoplasmic aggregates and improved neurite outgrowth, and were upregulated in cells expressing mutant SOD1.
- SOD1 D76V mutation identified in four family members predicts a long survival and shows genotype-phenotype correlation.
- The role of superoxide dismutase in human diseases is discussed [review]
- Erythrocyte analyses of CuZn-superoxide dismutase in D90A heterozygotes find no evidence that the putative protective factor in recessive families acts by downregulating the synthesis or altering the molecular structure or turnover of the mutant enzyme.
- Oxidation of select histidine residues that bind metals in the active site mediates SOD1 aggregation
- Mitochondrial localization of mutant enzyme triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis
- This mutation (H80A) is believed to alter zinc ligand binding, and its functional significance correlates well with the aggressive clinical course and postmortem findings.
- Sustained expression of mutant SOD1 leads to proteasomal inhibition and motor neuronal death, which in part explains the pathogenesis of mutant SOD1-linked ALS
- identifed and characterized key stability and structural differences resulting from the A4V mutation; architectural destabilization of the HSOD protein may underlie the toxic function of HSOD familial amyotrophic lateral sclerosis mutations
- Authors propose that a cis-acting regulatory polymorphism has arisen close to D90A-SOD1 in the recessive founder, which decreases ALS susceptibility in heterozygotes and slows disease progression.
- Malignsant lung tumors (squamous cell carcinoma and adenocarcinoma) had significantly decreased levels of this enzyme.
- Mutants of this enzyme in amyotrophic lateral sclerosis are susceptible to disulfide reduction.
- The cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, nitric oxide synthetic pathways and mutations in this enzyme.
- There is a novel mutation in this gene in a Korean family with amyotrophic lateral sclerosis.
- Expression is implicated in placenta development.
- Phenotypic effects of familial amyotrophic lateral sclerosis mutant alleles in transgsenic Drosophila
- Data show that overexpression of wild-type superoxide dismutase 1 in cells expressing mutant forms of the enzyme significantly enhanced cell survival and reduced apoptosis after serum deprivation.
- Cu-Zn superoxide dismutase is exported by microvesicular granules
- The large number of Cu/Zn SOD-related ALS mutations at residue 93 indicates that the loss of the glycine and not the addition of an alanine is an important factor in the pathology arising from G93A Cu/Zn SOD.
- Erythrocyte SOD activity and glutathione system are altered in men with new diagnosed BD. These alterations may be contributory factor for tissue damage associated with BD.
- results suggest that high glucose flux through aldose reductase inhibits the expression of catalase, CuZn superoxide-dismutase and glutathione peroxidase
- Overexpression of SOD1 increases release of TNF-alpha, VEGF, and metalloproteinases MMP-2 and MMP-9 from cultured, activated peritoneal macrophages, and increases TNF-alpha levels in the serum, as well as the delayed-type hypersensitivity response.
- This review is a critical survey of in vitro characteristics of over 30 of the 90 different CuZnSOD mutant proteins known to cause familial amyotrophic lateral sclerosis, in order to determine the differences between mutant and wild-type properties.
- the strong oxidant formed by hydrogen peroxide and SOD1 in the presence of bicarbonate arises from a pathway mechanistically distinct from that producing the oxidant in its absence.
- data suggest that endoplasmic reticulum stress is involved in the pathogenesis of familial amyotrophic lateral sclerosis with an SOD1 mutation
- Trp-32 oxidation is crucial for covalent aggregation of hSOD1 induced by bicarbonate mediated peroxidase activity
- In this paper provided the clinical and neuropathological feature os a FALS patient with the G37R mutation in exon 2 of the SOD1 gene.
- Caspase-1 and -3 mRNAs are differentially upregulated in motor neurons and glial cells in spinal cord of mice that are transgenic for this enzyme.
- structure of holo and metal-deficient wild-type human Cu, Zn superoxide dismutase
- SOD1 may contribute to the early activation of the Akt cell survival signaling pathway and may attenuate subsequent DNA damage after transient focal cerebral ischemia in human SOD1 transgenic mice
- Expression of G93A ALS-linked Cu,Zn superoxide dismutase mutant in neuroblastoma cells activates proteasomes and down-regulates neuronal nitric oxide synthase suggesting cross-talk between reactive oxygen and nitrogen species via the proteasome pathway
- Here we show that metal-deficient SOD1 mutant proteins crystallize in three different crystal forms, all of which reveal higher-order assemblies of aligned beta-sheets.
- SOD1 was elevated in diabetic patients with toenail infections treated with antioxidants and antifungal agents compared to healthy individuals.
- a new SOD1 mutation is identified in amyotrophic lateral sclerosis
- SOD1 was measured in the blood from patients with diabetes mellitus, insulin-dependent.
- Mechanisms of biosynthesis of copper/zinc superoxide dismutase
- The unfolding and refolding of a monomeric mutant of copper-zinc superoxide dismutase was investigated by NMR spectroscopy in the copper-reduced form and by using guanidinium chloride as denaturing agent
- Effects of overexpression of wild-type SOD-1 or the G37R or G85R mutations on the accumulation of ubiquitinated and nitrated proteins and on loss of cell viability induced by the proteasome inhibitor lactacystin were examined
- in normal human cells the SOD1 protein may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells
- Glycoaldehyde inactivates SOD1.
- overexpression of superoxide dismutase 1 protects against beta-amyloid peptide toxicity
- These results support free-cysteine-independent aggregation of FALS mutant SOD as a part of FALS pathology. They furthermore provide a molecular basis for the single FALS disease phenotype resulting from mutations of side-chains throughout the protein
- Mutant human SOD1 aggregates widely reported in neural tissues accumulate in hindlimb skeletal muscle of transgenic SOD1(G39A) mice in a model of amyotrophic lateral sclerosis.
- This study present three members of a pedigree with familial amyotrophic lateral sclerosis (FALS) who have a rare mutation in exon 4 of Cu/Zn superoxide dismutase (SOD1) codon position 89, converting alanine to valine.
- This study examined the clinical features of the first Italian FALS with the Leu144Phe SOD1 mutation. Seven affected members were identified in a six-generation pedigree.
- sixteen SOD1 mutations in amyotrophic lateral sclerosis bringing the total number of SOD1 gene mutations to 105.
- toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells; nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons
- The presence of G93A mutant human SOD1 in transgenic mice alters survival of phosphorylated-AKT kinase and -ERK kinase signals, possibly to compensate for the acquired gain-of-function of the mutant protein.
- Cu/Zn-SOD in cytosol and Mn-SOD in mitochondria each are capable of protecting HepG2 cells expressing CYP2E1 against cytotoxicity induced by pro-oxidants.
- SOD1(G93A) mutation in mice induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
- interaction among misfolded SOD1, NEDL1, translocon-associated protein-delta, and Dishevelled-1 forms a ubiquitinated protein complex that is included in potentially cytotoxic protein aggregates
- Overexpression of SOD1 in astrocytes rapidly reduces glutamate transporter GLT-1 levels due to a property shared between the wild-type and SOD1(G93A) mutant form that does not involve production of intracellular oxidative stress.
- Cu,Zn superoxide dismutase and nitric oxide synthase have roles in neurodegenerative processes (review)
- monomeric Cu,Zn-superoxide dismutase is a common misfolding intermediate in the oxidation models of sporadic and familial amyotrophic lateral sclerosis
- This study analyzed 33 fALS patients and found 10 mutations in SOD1 gene, in which two were novel: Asp101His substitution in exon 4 and Gly141Glu substitution in exon 5.
- Expression of alsin LF, but not alsin short form, protected motor neuronal cells from toxicity induced by mutants of the Cu/Zn-superoxide dismutase (SOD1) gene, which cause autosomal dominant ALS
- 15% of amyotrophic lateral sclerosis cases are associated with an abnormality in the SOD1 gene. (REVIEW)
- Silencing of mutant SOD1 protects cells against cyclosporin A-induced cell death.
- reduced NO-superoxide interaction in SOD-transgenic-db/db mice.
- In transgenic mice the SOD1 G93A mutation causes changes in the AMPA-receptor expression and function, as well as susceptibility to kainate-mediated excitotoxicity, which may promote the motor neuron degeneration seen in ALS
- Combined increase in amyloid precursor protein (APP) and SOD1 in a double-transgenic (tg)-APP-SOD1 mouse results in severe impairment in learning, working and long-term memory.
- N139H is the fifth SOD1 gene mutation reported in Spain, and the first one presenting with incomplete penetrance.
- the two SOD1 mutants, by an unknown mechanism, promote the dispersion of the golgi apparatus and the dysfunction of the secretory pathway
- Awake parameters in mice transgenic for human SOD-1 (S/+) are the same in S/+ and control mice, whereas paradoxical sleep (PS) decreased and PS latency increased after lights off in S/+ mice.
- An intersubunit disulfide bond prevents in vitro aggregation of a SOD1 mutant linkd to familial amyotrophic lateral sclerosis.
- HCO(3)(-)-derived oxidant does not alter significantly the Cu(II) active site geometry and histidine coordination to Cu(II) in SOD1 as does H(2)O(2) alone
- Review. Blood vessels express 3 isoforms of superoxide dismutase, 1 of which is cytosolic or copper-zinc SOD. This review will focus mainly on the role of individual SODs in relation to endothelium under normal conditions and in disease states.
- Data show that G93A superoxide dismutase (SOD), like wild-type SOD, protects calcineurin against inactivation.
- Erythrocyte superoxide dismutase activity was found to be significantly lower in patients with pneumothorax than in the control group.
- Lateral sclerosis G93A SOD1 amino acid substituted transgenic mice show a metabolic deficit and skeletal muscle hypermetabolism, controlled by a highly energetic diet which extended survival
- When transfected into mice, induces mitochondrial swelling, vacuolization, or learning and memory deficits.
- the immature brain has limited GPX activity and is more susceptible to oxidative damage and may explain the paradoxical effect seen in ischemic neonatal brain when SOD1 is overexpressed.
- peroxynitrite reacts with CuZnSOD leading to nitrogen dioxide plus a copper-bound hydroxyl radical species that reacts with histidine residues, forming histidinyl radical
- Data show that reduction leads to a change in the quaternary structure of superoxide dismutase 1, decreasing the monomer-to-dimer equilibrium constant by at least four orders of magnitude.
- Cu, Zn- and MnSOD levels were significantly increased in frontal cortex and substantia innominata of the index group in schizophrenia
- SOD1 G93A mutation, leading to amyotrophic lateral sclerosis in humans and mice, does not necessarily worsen neuronal degeneration in other pathologies.
- Results suggest that co-chaperone CHIP, possibly with another E3 ligase(s), modulates the ubiquitylation of mutant Cu/Zn-superoxide dismutase and renders them more susceptible for proteasomal degradation.
- In transgenic mice, shows neuron degeneration and brain atrophy in a mouse model of lateral sclerosis.
- Familial amyotrophic lateral sclerosis with His46Arg mutation in Cu/Zn superoxide dismutase presenting characteristic clinical features and Lewy body-like hyaline inclusions.
- The present study demonstrated that both SOD1 and the metal-free form of enzyme (Apo SOD1) inhibit HMG-CoA reductase gene expression in HepG2 cells, in normal human fibroblasts, and in fibroblasts of subjects affected by familiar hypercholesterolemia.
- SOD1 carries out a neuromodulatory role affecting calcium-dependent cellular functions
- familial amyotrophic lateral sclerosis-linked SOD1 aggregation occurs by a mutation-induced increase in dimer dissociation and/or increase in apomonomer formation
- combining sedimentation data with previous crystallographic results, a molecular explanation is provided for existence of different copper-zinc superoxide dismutase (SOD1) macromolecular shapes and multiple dimeric species with different stabilities
- Expression of a familial amyotropic lateral sclerosis-associated mutant SOD1 in yeast leads to decreased mitochondrial transport.
- mutant SOD1 but not the wild type bound directly to the neurofilament mRNA 3'-untranslated region and that the binding was necessary to induce mRNA destabilization
- impaired ability to form, or retain, the C57-C146 bond in vivo is predicted to increase the cellular load of marginally stable apoSOD monomers, which may have implications for the amytrophic lateral sclerosis neuropathology
- Deficiency in mice increased cell proliferation in the presence of persistent oxidative damage to macromolecules contributes to hepatocarcinogenesis later in life.
- Sod1 knockout mice develop hepetocellular carcinoma and exhibit a 30% reduction in lifespan.
- SOD expression in endothelial cells attenuates TNF-alpha-induced superoxide production & adhesion molecule expression by decreasing JNK & p38 phosphorylation and AP-1 & NF-kB inactivation. SOD may play a role in preventing atherosclerosis & inflammation.
- Rac1, PI3 kinase, and Akt3 have roles in an anti-apoptotic pathway triggered by ALS2 that antagonizes SOD1 mutant-induced motoneuronal cell death
- 4 SNPs (-3392G/T, +2811G/A, +6782 A/C, & +18636C/G)and a 50 bp deletion, -1684del, showed no association with sporadic amyotrophic lateral sclerosis phenotype or susceptibility.
- Cu-Zn superoxide dismutase expression in humans is detected in pulmonary epithelial cells by Western blot.
- These results suggest novel extracellular roles for SOD1 in amyotrophic lateral sclerosis and support a causal relationship between mutant SOD1 secretion and intraneuronal toxicity.
- mutant SOD1 overexpression promotes neither beta-amyloid toxicity nor brain accumulation in amyotrophic lateral sclerosis models
- the earliest disulfide-reduced polypeptides in the SOD1 assembly pathway are most destabilized with respect to unfolding and oxidative aggregation by amyotrophic lateral sclerosis-causing mutations
- Superoxide dismutase is inactivated in asthmatic airway remodeling
- Mutant SOD1 proteins may impair chaperone function independent of gene expression in vivo, and this inhibition may be a shared property of amyotrophic lateral sclerosis-linked mutant SOD1 proteins.
- Accumulation of soluble and detergent-insoluble mutant SOD1 in spinal cord of symptomatic SOD1G93A transgenic mice is due to impaired degradation of mutant SOD1 rather than to increased transcript levels.
- In addition to being in the mitochondrial outer membrane and intermembrane space, SOD1 is also localized in the mitochondrial matrix of brain mitochondria
- Within FALS(familial amyotrophic lateral sclerosis) cases, The most frequent mutation was the G41S identified in four FALS.
- SOD1 mutants gain fatty acid binding abilities based on their structural instability and form cytotoxic granular aggregates
- pyruvate significantly reduced the death and production of reactive oxygen species in cells expressing mutant SOD1
- Overexpression of human copper/zinc-superoxide dismutase reduces oxidative stress with a subsequent decrease in apurinic/apyrimidinic endonuclease expression.
- the pathogenesis of increased oxidative stress differs between sporadic amyotrophic lateral sclerosis patients and familial ALS patients with a mutant Leu126Ser SOD1 gene.
- In SOD1 Tg mice, MCP-1 and MIP-1 alpha mRNA expression was significantly decreased 12 h postinsult
- Brachial amyotrophic diplegia is associated with a novel SOD1 mutation (L106P).
- Adenovirus-mediated gene transfer of superoxide dismutase and catalase reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.
- FAS overexpression was significantly reduced in cortex of transgenic mice overexpressing both wild-type hAPP gene & wild-type human superoxide dismutase-1 gene. hSOD-1 expression was associated with increase of Glial fibrillary acidic protein production.
- Oxidized SOD1 inhibits purified proteasome peptidase activities and may be partially responsible for proteasome inhibition shown in SOD1 transgenic mice.
- Genetic variants of the SOD gene is associated with insulin resistance and the susceptibility to type 2 diabetes.
- Truncated human SOD1 is associated with motor neurons disease in mice
- Overexpression of wild-type human SOD1 blocked motor neuron apoptosis. Injured MNs in mice harboring mutant human SOD1 had upregulated Fas and iNOS, more DNA damage, & accelerated & increased MN degeneration & underwent necrosis instead of apoptosis.
- ALS-mutant apoproteins are not universally destabilized by the disease-causing mutations.
- The establishment of this SOD1-G37R cDNA transgenic model indicates that expression of mutant SOD1 proteins in the neuromuscular unit is sufficient to cause motor neuron disease.
- Using different cell lines of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1, we show that the removal of Apaf1 prevents cells death.
- mutant SOD1 and truncated SOD1 lead to neural cell death because of misfolding, and SOD1 peptides, possibly as a result of proteolytic digestion of mutant SOD, play a role in pathogenesis in amyotrophic lateral sclerosis
- SOD1 deficiency impairs H2O2-mediated activation of NF-kappaB, decreasing death-promoting signals, and leading to better outcome.
- analysis of S134N Cu,Zn-superoxide dismutase and its mobility and intermolecular contacts in solution
- The copper chaperone CCS is responsible for copper insertion into apo-SOD1.
- heparin-released EC-SOD is significantly reduced in coronary artery atherosclerosis
- solution structure of the copper-depleted, disulfide-reduced form of human SOD1
- The authors analyzed the relative amount of mutant compared with normal SOD1 protein in the erythrocytes from 29 patients with ALS with 22 different mutations. Turnover of mutant SOD1 correlated with a shorter disease survival time.
- Data raise suggest that in a cellular environment with low availability of free copper, Zn-Zn may be the preferred metallation state of superoxide dismutase 1 prior to its interaction with the copper chaperone.
- Glycine 93 mutants of superoxide dismutase (SOD) 1 have an increased propensity to misfold or aggregate, which may be linked to increased toxic mutant SOD aggregation in familial amyotrophic lateral sclerosis.
- Sporadic amyotrophic lateral sclerosis and breast cancer: Hyaline conglomerate inclusions lead to identification of an I113T SOD1 mutation.
- the phenotypic spectrum of ALS associated with SOD1(G72C) mutations to include presenting features that mimic a myopathy.
- marker of severity in the very early stages of acute pancreatitis
- The expression of SOD1 was higher in polyp tissues. These results are consistent with previously reported data and support the hypothesis that there is increased oxidative stress in NP.
- caspase-3 cleavage of EAAT2 is one mechanism responsible for the impairment of glutamate uptake in mutant SOD1-linked amyotrophic lateral sclerosis
- various mutations have different effects on SOD1 aggregation potential and the H80G mutation appears to uniquely act as a dominant inhibitor of SOD1 aggregation.
- The activity of erythrocyte Cu/Zn SOD was altered in type 2 diabetic patients.
- overexpression of Cu, Zn-SOD and/or catalase in smooth muscle cells attenuates the cell proliferation caused by oxLDL stimulation
- Data show a molecular mechanism by which SOD1 is converted to aggregated and apparently ALS-associated toxic dimers and multimers by redox processes.
- In the disulfide-reduced form, A4V apoSOD1 exchanged like a "random coil" polypeptide at 20 degrees C and began to populate folded states at 4 degrees C.
- Sod1 knockout mice have a dramatic accleration of age related muscle mass loss and a 20% reduction in body weight.
- Ribonucleoprotein complex formation on SOD1 mRNA as a neuronal tissue-specific and Amyotrophic lateral sclerosis associated mutation.
- expression of SOD1 within motor neurons was shown to be a primary determinant of disease onset and of an early phase of disease progression
- The results of this study revealed that, MPO, XO and SOD conditions in gastric mucosa alone were not affected from HP presence. That's why MPO, XO, and SOD may not have important roles in the pathogenesis of HP related gastric disease in children.
- the localization of Cu/Zn- and Mn-SODs in adrenal tissues reflects the specificity of the adrenal cells that produce the tissue-specific hormones
- structure of this putative ALS precursor is strikingly similar to those implicated in amyloid disease
- In rat mutants, a significant up-regulation of unfolded protein response entities was observed during disease, including several caspases.
- By crossing this transgenic line with mice that express SOD1(G93A) and mice that express wild-type human SOD1, we found that this shRNA specifically silences the mutant, but not the wild-type SOD1
- A unique genomic deletion within intron 2 close to the 5' splice junction of the SOD1 gene was identified in three patients with KC.
- there is a critical balance between cellular reductants such as glutaredoxin and copper activation pathways in controlling the disulfide and stability of SOD1 in vivo
- TNF-alpha down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway
- Our results suggest that mitochondrial vulnerability of motoneurons to G93ASOD1 is recapitulated in NSC-34 cells, and that peculiar features in network dynamics may account for the selective alterations of motoneuronal mitochondria.
- both macroautophagy and the proteasome are important for the reduction of mutant SOD1-mediated neurotoxicity in amyotrophic lateral sclerosis
- ubiquitination occurs only after SOD1 aggregation
- 12 different familial amyotrophic lateral sclerosis mutant SOD1s with widely differing biophysical properties are associated with mitochondria of motoneuronal cells.
- Comparison of the clinical characteristics with previously reported sporadic amyotrophic lateral sclerosis (ALS) patients carrying the same or similar SOD1 gene mutations showed a remarkable genotype-phenotype correlation.
- This study identified a heterozygous mutation of ATT to ACT of SOD1 gene at codon 149 in exon 5 resulting in substitution of isoleucine to threonine.
- Our data suggest that deficiency in the ALS2 gene does not affect the pathogenesis of SOD1(G93A) mice.
- Mean relative levels of SOD1 & its mRNA were significantly decreased in women > or =38 years, which may account for granulosa-cell changes associated with reproductive aging.
- Human neural stem cells transplanted into rats transgenic for SOSD1 the lifespan of fulminant motor neuron disease animals.
- CuZnSOD activity was significantly lower in gastric adenocarcinoma samples with respect to normal mucosa. The rate of MnSOD/CuZnSOD activity in adenocarcinoma was over ninefold higher than that registered in healthy tissues
- Diabetes significantly suppressed PGIS activity in parallel with increased superoxide and PGIS nitration in the aortas of diabetic C57BL6 mice but had less effect in diabetic mice either lacking eNOS or overexpressing human SOD.
- analysis of the acute and rapid endothelial cell endocytosis of CuZn-SOD via activation of a receptor-mediated pathway
- mutations at copper ligand histidine residues of superoxide dismutase 1 diminish the binding of copper and compromise dimer stability
- Stable overexpression of SOD1 caused significant decreases in superoxide and nitric oxide production, with concurrent increases in hydrogen peroxide following LPS. Important role in redox-sensitive inflammatory signaling and neurotoxic inflammation.
- Modification of cysteine 111 in human Cu,Zn-superoxide dismutase.
- Dorfin-CHIP(L) rescued neuronal cells from mutant SOD1-associated toxicity and reduced the aggresome formation induced by mutant SOD1 more effectively than did Dorfin(WT).
- SOD1-mutant-mediated damage within muscles is not a significant contributor to non-cell-autonomous pathogenesis in ALS, and enhancing muscle mass and strength provides no benefit in slowing disease onset or progression.
- Systemic activity of the enzymatic antioxidants (CuZn/SOD, MnSOD, GSH-Px, and CAT) as well as level of lipid peroxidation determined by MDA may not be increased in the course of immune-inflammatory processes associated with chronic idiopathic urticaria.
- Impaired post-translational folding is found in familial ALS-linked Cu, Zn superoxide dismutase mutants.
- We report a novel missense mutation (Asp109Tyr) in exon 4 of the Cu/Zn superoxide dismutase (sod1) gene in a woman with apparently sporadic amyotrophic lateral sclerosis (SALS).
- Overexpression of transgenic SOD1 in hyperglycemic rats reduces blood-brain barrier permeability and matrix metalloproteinase-9 activation after transient focal cerebral ischemia.
- Motor terminals innervating fast hindlimb muscles in male SOD1-G93A mice become especially susceptible to ischemia/reperfusion injury at a young age.
- Novel SOD1 N86K mutation is associated with a severe phenotype in familial ALS.
- Data show that activation of brain calcineurin (Cn) by Cu-Zn superoxide dismutase (SOD1) depends on direct SOD1-Cn protein interactions occurring in vitro and in vivo.
- Occurrence of severe abnormalities, such as cell fusions and cytorrhexis, in microglia of SOD1G93A transgenic rats may be the result of expression of mutant SOD1 in these cells.
- in vivo evidence correlates mutation of the SOD1 gene to increased nitric oxide, nitration and oxidation of proteins in amyotrophic lateral sclerosis
- communication between the two monomers of SOD1 such that the binding of one zinc ion per homodimer has a more profound effect on the homodimeric protein structure than the binding of subsequent metal ions
- These data suggest that mitochondrial-produced O(2) (*) radicals play a critical role in mutant SOD1-mediated neuronal toxicity and implicate mitochondrial-produced free radicals as potential therapeutic targets in ALS.
- These results demonstrate that altered SOD1 activity (mSOD(G93A)) in BMDCs affects striatal damage probably through a mechanism involving a systemic factor.
- Cortical 5-HT1A receptor binding in patients with homozygous D90A SOD1 vs sporadic ALS.
- mutation evaluation & clinical features examination in a Korean family with amyotrophic lateral sclerosis; a point mutation in exon 1 of the SOD1 gene, resulting in an amino acid change from phenylalanine 20 to cysteine, was identified
- therefore examined the methylation status of two genes, SOD1 and VEGF, which are implicated in ALS.
- overexpression of SOD1 in the Tg rats results in an increase in endogenous pPRAS40 and a decrease in motor neuron death through the PI3K/Akt pathway.
- Alteration of these mutant SOD1-induced pathways identified a set of targets for therapies for inherited Amyotrophic Lateral Sclerosis
- the absence of pathological TDP-43 in cases with SOD1 mutations implies that motor neuron degeneration
- This is a first case of slowly progressing amyotrophic lateral sclerosis caused by H46R SOD1 mutation of Parkistani descent.
- SOD1 mutation has a role in amyotrophic lateral sclerosis
- copper/zinc superoxide dismutase mutations preferentially reduce the repulsive charge of the proteins in amyotrophic lateral sclerosis
- Molecular dynamics using atomic-resolution structure reveal structural fluctuations that may lead to polymerization of SOD.
- H46R mutant SOD1 transgenic mice are characterized by widespread pathologic changes of the spinal cord that extend beyond the motor system, including many aggregates lacking vacuoles.
- Mutations determine age of onset of amyotrophic lateral sclerosis.
- Thus, relative to wild-type microglia, mSOD1(G93A) microglia were more neurotoxic and induced more motoneuron injury than similarly treated wild-type microglia.
- This data suggests that the regulation of O2(.-) is located at the crossroads between LDL signaling and cell proliferation.
- Absence of zinc and copper ions is clearly a major factor determining the propensity of SOD1 protein to oligomerize and form the toxic species that may cause SOD1-linked amyotrophic lateral sclerosis.
- This study demonstrates a homogeneous overexpression of the genes encoding for SOD in nuchal skin of human trisomy 21 fetuses.
- The missense mutation of SOD1 gene in two of the three alleles could have increased its toxic effects in the Down syndrome patient leading to an earlier onset and rapid progression of the disease.
- identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between sporadic Amyotrophic lateral sclerosis (ALS) and familial ALS
- Overexpression of mutant human SOD1 in zebrafish embryos induced a motor axonopathy that was specific, dose-dependent and found for all mutations studied.
- Our data suggest that this TATA box defect is not a disease-causing mutation or susceptibility factor for ALS but rather a rare polymorphism with a potential effect on SOD1 gene expression.
- No significant association with prostate cancer was observed for polymorphic variants in SOD1.
- Mutant SOD1 gains a novel function possibly by altering the ribonucleoprotein complex with vascular endothelial growth factor (VEGF) 3'-untranslated region in amyotrophic lateral sclerosis transgenic mice.
- SOD1 weakly increased the rate of decomposition of S-nitrosylated glutathione
- Suggest that higher circulating Cu/Zn SOD could protect type 1 diabetes mellitus children/adolescents against endothelial dysfunction. Low Cu/Zn SOD is a potential early marker of susceptibility to diabetic vascular disease.
- The increased plasticity of the apo G37R asSOD1 mutant protein is responsible for its enhanced tendency to aggregate in concentrated solutions. These results suggest that metal-free apo forms of the mut. SOD1 protein are the agents of its toxicity.
- superoxide dismutase 1 mRNA levels were reduced in peripheral mononuclear cells after copper supplementation
- The level of LC3-II, which is known to be correlated with the extent of autophagosome formation, was increased in SOD1G93A transgenic mice at symptomatic stage compared with non-transgenic or human wild-type SOD1 transgenic animals.
- Transgenic mice form a least common denominator amongst SOD1 mutants with widely different molecular characteristics and might be involved in the cytotoxicity that causes lateral sclerosis.
- SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content and is associated with amyotrophic lateral sclerosis
- After intravenous injection into irradiated pre-symptomatic SOD1-G93A mice, hMSC survived more than 20 weeks in recipient mice, migrated into the parenchyma of brain and spinal cord and showed neuroglia differentiation.
- Results suggest that the sumoylated COOH terminus of EAAT2 associates with the promyelocytic leukemia nuclear bodies in hSod1 mutatnt transgenic mice.
- The crystal structure of a zinc-deficient human SOD shows that its stabilization as a heterodimer with Cu,Zn SOD may contribute to the dominant inheritance of ALS mutations.
- A nmultinuclear copper (I) cluster forms the dimerization interface in copper-loaded human copper chaperone for SOD1.
- Multiple variations (single nucleootide polymorphisms0 in SOD1 are significantly associated with persistent microalbuminuria and severe nephropathy.
- the Lewy body-like hyaline inclusion/astrocytic hyaline inclusion in mutant SOD1-linked familial amyotrophic lateral sclerosismay arise from ER dysfunction
- To understand the role of SOD1 mutations in the pathophysiol of FALS we compared the pattern of proteins expressed in human neuroblastoma cells with those of cell lines transfected with plasmids expressing the wild-type SOD1 and the H46R and G93A mutants
- This is the first report in which the presence of SOD1 (iso) forms in a cellular model of ALS has been evidenced.
- Our results provide the first cell-by-cell-analysis of SOD1 ubiquitination and chaperone interaction
- Removal of Cysteine-111 impairs the ability of mutated SOD1 to form disulfide cross-linking is associated with familial amyotrophic lateral sclerosis.
- Evidence for different pattern of cortical neuronal vulnerability in homD90A SOD1 amyotrophic lateral sclerosis(ALS) versus sporadic ALS that may provide insight as to their slower rate of disease progression.
- Transgenic mice that have a restricted expression of mutant SOD1 have pathological abnormalities of motor neurons confined to cells that express mutant SOD1.
- The conserved minimal haplotype is statistically more similar to Asian than European population DNA sets, suggesting that the SOD1 A4V mutation arose in native Asian-Americans who reached the Americas through the Bering Strait.
- A genome-wide association study of sporadic ALS in a homogeneous Irish population was conducted.
- Consistent with the altered morphology of Prefrontal cortical regions, SOD1 mutant mice showed impaired extinction of conditioned fear.
- From case study this study suggested degeneration of the dentatorubral system and the absence of LBHIs in our case are pathological features in FALS with the Gly93Ser mutation.
- principal protein in the high molecular mass aggregates whose appearance correlates with symptoms of the disease is the unmodified, full-length SOD1 polypeptide
- Toxicity of mutant SOD1 is partially mediated through heterodimer formation with SOD1(hWT) in vivo and does not correlate with the aggregation potential of individual mutants.
- Misfolding of amyotrophic lateral sclerosis-related mutant SOD1 induces endoplasmic reticulum stress, which may contribute to the motor neuron degeneration in amyotrophic lateral sclerosis pathogenesis.
- SOD1 is essential for the preservation of cytoskeleton integrity
- Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson's disease.
- These findings demonstrate that mutant SOD1 astrocytes are viable targets for therapies for slowing the progression of non-cell autonomous killing of motor neurons in ALS.
- Our data indicate that studies from referral centers may overestimate the frequency of familial ALS and of SOD1 mutations in sporadic ALS.
- SOD1 glycine93aspartate mutation, found in DNA extracted from the hair bulbs in two deceased obligate carriers, causes a slowly developing lower motor neuron disease with a reduced penetrance.
- Gain-of-function mutations in the Cu,Zn-superoxide dismutase (SOD1) gene are implicated in progressive motor neuron death and paralysis in one form of inherited amyotrophic lateral sclerosis (ALS).
- pathological characterized pathological SOD1 mutants byinvestigating their propensity to aggregation
- The results suggest that SOD Ala16Val polymorphism is an age-dependent modulator of ox-LDL-C levels in middle-aged men and elderly women.
- Results describe the activity of ferroxidase, SOD1, and cofactors in CSF of patients with Parkinson's disease, Alzheimer's disease, Huntington's disease, or amyotrophic lateral sclerosis.
- disulfide cross-linking has a limited roled in the aggregation of mutant SOD1 linked to familial amyotrophic lateral sclerosis
- Results investigate the role of mutant SOD1 in familial ALS by fusing human SOD1 genes with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins.
- These results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.
- Endoplasmic reticulum-golgi apparatus pathway is a predominant cellular site of aggregation of mutant SOD1 suggests that secretion could play a key role in pathogenesi of lateral sclerosis.
- the interference with axonal transport and protein turnover by mutant SOD1 could influence the function and viability of motor neurons in ALS.
- Polymorphisms of CuZn-SOD, MnSOD, GSTM1 and GSTT1 in the placental tissue were not associated with preeclampsia.
- Measurements of hCCS-induced SOD1 activation were used to show that the C-terminal CXC sequence is both necessary and sufficient for EZn-SOD maturation.
- The primary factor causing the oxidative stress observed in rheumatoid arthritis and systemic lupus erythematosus is excessive free radical production rather than impaired catalase or superoxide dismutase activity due to autoantibody inhibition.
- genotype distribution of the SOD1 in patients with diabetes mellitus can differ from nondiabetic individuals
- These data have demonstrated that a 'mini-SOD1' of only 115 amino acids is sufficient to cause ALS.
- The phenotypic variability between SOD1 mutation carrying patients in this study is dramatic, even among patients with the same mutation.
- SOD1 is a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth
- evidence of biochemical changes in the hindlimb muscle of young, presymptomatic G93A hSOD1 transgenic mice in an amyotrophic lateral sclerosis model
- Novel genetic variants were found in 30% brains and known variants in 91% brains from patients with SALS. Two novel variants found in SALS patients were located in the SOD1 promoter and intron 1.
- The misfolded SOD1s directly perturb axonal transport or impair other functional properties of the dynein motor which may cause motor neuron death in lateral sclerosis.
- copper chaperone for SOD1 (CCS) facilitates maturation of SOD1 and that CCS overexpression ameliorates intracellular aggregation of mutant SOD1 in vivo.
- ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1), and transgenic overexpression of human superoxide dismutase 1 (SOD1) prolonged incubation times by 13, 16 and 19 %, respectively.
- potential gender difference in levels of SOD1 in CSF of ALS(amyotrophic lateral sclerosis) patients
- BICD2-N transgene increased lifespan in 'low copy' SOD1-G93A ALS transgenic mice.
- study reports that nNOS overexpression induced a NO-dependent increase in the concentration of intracellular glutathione and a NO-independent down-regulation of SOD1 in terms of mRNA, protein and activity level
- Expression of wild type or disease-linked (A4V, G85R) mutants of human SOD1 selectively in motor neurons induced progressive climbing deficits.
- SOD1 protein may modify the phenotype of SALS within selected populations
- Genetic analysis revealed three amyotrophic lateral sclerosis patients (1.8%) with mild phenotype carrying the homozygous D90A mutation of superoxide dismutase 1.
- These results support the hypothesis that aberrant copper chemistry through a cysteine residue plays a critical role in mutant SOD1 toxicity and that TTM may be a promising therapy for familial ALS with SOD1 mutants.
- In conclusion, despite the protective action against acute motor neuron injury, Hsp27 alone is not sufficient to protect against the chronic motor neuron injury due to the presence of mutant SOD1.
- Findings show that Cu/Zn-superoxide dismutase aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival.
- The astrocyte-specific gene expression profile in SOD1-mutant animals might contribute to the identification of possible candidates for cell type-specific therapies in ALS.
- DNAs tested are simultaneously condensed into a nanoparticle with a specific morphology during SOD1 aggregation, revealing that SOD1 aggregation and DNA condensation are two concurrent phenomena.
- in mammalian cells, SOD1 mitochondrial localization is dictated by its folding state, which is modulated by several interconnected factors
- mitoKARS is the first described member of a group of mitochondrial proteins whose interaction with mutant SOD1 contributes to mitochondrial dysfunction in ALS
- the rates of metal release during SOD1 unfolding in guanidine hydrochloride.
- SOD1 and SOD2 expressions demonstrate how sex and daytime, merit being controlled when human gene expression analyses are evaluated, particularly within the framework of clinical trials or cohort studies.
- SOD1-overexpressing human glioma cells are radioresistant; its overexpression suppresses late ROS accumulation in irradiated cells, and the radioresistance is associated with enhanced G2 accumulation and decreased cyclin B1 mRNA and protein levels
- Superoxide-dismutase was increased in benign hyperplasia of prostate and decreased in prostate cancer.
- sod mutation have been associated with amyotrophic lateral sclerosis and parkinson disease-{review}
- Ubiquitin-proteasome system impairment occurs in transgenic mice expressing mutant human Sod1 during amyotrophic lateral sclerosis progression.
- The approximately 100-fold increase in the rate of folding of SOD in the presence of micromolar concentrations of zinc demonstrates a significant role for a preorganized zinc-binding loop in the transition-state ensemble.
- Increased superoxide dismutase 1 expression is associated with multiple sclerosis lesions.
- The results reveal the kinetic basis for the extremely high stability of wild-type holo SOD and the possible consequences of kinetic changes for disease.
- Superoxide scavenging with adenovirus-mediated transfer of Cu/ZnSOD in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction.
- We describe a patient with ALS and muscle mitochondrial oxidative defect associated with a novel SOD1 mutation. Revealed a heterozygous mutation in codon 22 substituting a highly conserved amino acid, from glutamine to arginine (Q22R).
- Data show that a small amount of disulfide-reduced apo-superoxide dismutase 1 can rapidly initiate fibrillation under mild, physiologically accessible conditions.
- We show that NOX2 inhibitor, apocynin, can prevent the loss of motor neurons caused by SOD1-mutated astrocytes. These results provide an assay for drug screening using a human ALS in vitro astrocyte-based cell model.
- Mitochodrial disruptions are critical elements of SOD1(G93A)-mediated motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis.
- Data show that SOD1 is decreased in the CSF of temporal lobe epilepsy patients.
- Patients with homozygous D90A SOD1 ALS showed less extensive pathologic white matter in motor and extramotor pathways compared with patients with sporadic ALS.
- early consequence of the association of SOD1-G85R or SOD1-G93A with motoneuronal mitochondria is reduced capacity of the ETC to limit Ca(2+)-induced Psi(m) depolarization; this impairment contributes to disease progression in mutant SOD1 motor terminals.
- Animal modles with mutations in this gene develop pathology similar to amyotrophic lateral sclerosis[REVIEW]
- These findings reveal a hitherto unknown IFN-beta/SOD1 axis in Leishmania infection
- In our Belgian cohort of FALS patients, SOD1 mutations were responsible for 35% of all cases while TARDBP was only identified in one family and therefore seemed to account for just a minority of FALS (3%) in this population.
- Mutations in the genetic background strongly enhanced the toxicity of huamn SOD1 mutants expressed in Caenorhabditis elegans.