Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UNIPROT:P30044 (antioxidant enzyme)
8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glyoxalase-1 (Glo1) is an antioxidant enzyme which detoxifies alpha-ketoaldehydes to prevent the accumulation of pro-oxidant compounds, such as methylglyoxal, in all cell types. Glo1 has been suggested to be involved in anxiety disorders, autism, and Alzheimer's disease. Mood disorders have a high rate of comorbidity with anxiety disorders although, to date, little is known of the involvement of Glo1 in the pathophysiology of these conditions. In the present study, we examined the expression levels of Glo1 mRNA in peripheral white blood cells of mood disorder patients to understand the role of Glo1 in mood disorders. Quantitative real-time polymerase chain reaction experiments revealed that reduced expression of Glo1 mRNA was observed in major depressive and bipolar disorder patients in a current depressive state, as compared with healthy control subjects. In contrast, the expression of Glo1 mRNA in major depressive and bipolar patients, in a remissive state, showed no significant alteration when compared with healthy control subjects. These results suggest that the aberrant expression of Glo1 might be involved in the pathophysiology of mood disorders.
...
PMID:Reduced expression of glyoxalase-1 mRNA in mood disorder patients. 1845 73

Quercetin, a flavonoid found in various foodstuffs, has antioxidant properties and increases glutathione (GSH) levels and antioxidant enzyme function. Considerable attention has been focused on increasing the intracellular GSH levels in many diseases, including Alzheimer's disease (AD). Amyloid beta-peptide [Abeta(1-42)], elevated in AD brain, is associated with oxidative stress and neurotoxicity. We aimed to investigate the protective effects of quercetin on Abeta(1-42)-induced oxidative cell toxicity in cultured neurons in the present study. Decreased cell survival in neuronal cultures treated with Abeta(1-42) correlated with increased free radical production measured by dichlorofluorescein fluorescence and an increase in protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation (protein-bound 4-hydroxy-2-nonenal). Pretreatment of primary hippocampal cultures with quercetin significantly attenuated Abeta(1-42)-induced cytotoxicity, protein oxidation, lipid peroxidation and apoptosis. A dose-response study suggested that quercetin showed protective effects against Abeta(1-42) toxicity by modulating oxidative stress at lower doses, but higher doses were not only non-neuroprotective but also toxic. These findings provide motivation to test the hypothesis that quercetin may provide a promising approach for the treatment of AD and other oxidative-stress-related neurodegenerative diseases.
...
PMID:Protective effect of quercetin in primary neurons against Abeta(1-42): relevance to Alzheimer's disease. 1860 17

The amyloid beta-peptide (Abeta)-induced oxidative stress is a well-established pathway of neuronal cell death in Alzheimer's disease (AD). Salidroside, one of the major compounds from the roots of Rhodiola species (Crassulaceae), was investigated in vitro for its cytoprotection against Abeta-induced toxicity on rat neuronal PCl2 cells. Salidroside significantly reduced Abeta-induced cytotoxicity in a dose-dependent manner. Salidroside also reduced Abeta-mediated intracellular accumulation of reactive oxygen species and malondialdehyde (MDA), a product of lipid peroxides, by preventing Abeta-induced decline of antioxidant enzyme activities. These results suggest that salidroside protects neuronal PC12 cells from Abeta-induced cytotoxicity via its antioxidant pathway.
...
PMID:Salidroside from Rhodiola sachalinensis protects neuronal PC12 cells against cytotoxicity induced by amyloid-beta. 1918 Jul 94

In Alzheimer's disease (AD), oxidative stress is present early and contributes to disease pathogenesis. We previously reported that in Tg19959 transgenic AD mice, partial deficiency of the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) exacerbated amyloid pathology. We therefore asked whether MnSOD overexpression would prove beneficial against AD pathogenesis, by studying the offspring of Tg19959 mice crossed with MnSOD-overexpressing mice. At 4 mo of age, there was a 2- to 3-fold increase in MnSOD protein levels in Tg19959-MnSOD mice compared to Tg19959 littermates. Tg19959-MnSOD mice also had a 50% increase in catalase protein levels, a 50% decrease in levels of oxidized protein, and a 33% reduction in cortical plaque burden compared to Tg19959 littermates. Spatial memory was impaired and synaptophysin levels were decreased in Tg19959 mice compared to wild-type littermates, but memory and synaptophysin levels were restored to wild-type levels in Tg19959-MnSOD littermates. These benefits occurred without changes in sodium dodecyl sulfate-soluble or formic acid-soluble Abeta pools or Abeta oligomers in Tg19959-MnSOD mice compared to Tg19959 littermates. These data demonstrate that facilitation of the mitochondrial antioxidant response improves resistance to Abeta, slows plaque formation or increases plaque degradation, and markedly attenuates the phenotype in a transgenic AD mouse model.
...
PMID:Reduction of oxidative stress, amyloid deposition, and memory deficit by manganese superoxide dismutase overexpression in a transgenic mouse model of Alzheimer's disease. 1934 95

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the degeneration of motor neurons. Mutations in Cu/Zn superoxide dismutase (SOD1), including G93A, were reportedly linked to familial ALS. SOD1 is a key antioxidant enzyme, and is also one of the major targets for oxidative damage in the brains of patients suffering from Alzheimers disease (AD). Several lines of evidence suggest that intracellular amyloid beta (Abeta) is associated with the pathogenesis of AD. In this report we demonstrate that intracellular Abeta directly interacts with SOD1, and that this interaction decreases the enzymatic activity of the enzyme. We observed Abeta-SOD1 aggregates in the perinuclear region of H4 cells, and mapped the SOD1 binding region to Abeta amino acids 26-42. Interestingly, intracellular Ab binds to the SOD1 G93A mutant with greater affinity than to wild-type SOD1. This resulted in considerably less mutant enzymatic activity. Our study implicates a potential role for Abeta in the development of ALS by interacting with the SOD1 G93A mutant.
...
PMID:Intracellular amyloid beta interacts with SOD1 and impairs the enzymatic activity of SOD1: implications for the pathogenesis of amyotrophic lateral sclerosis. 1947 59

Selenium reportedly contribute to the modulation process of protein phosphorylation to regulate various cellular functions including growth, differentiation, proliferation and development. The aim of this study was to investigate whether selenium and Selenoprotein M (SelM) affects the mechanism of Alzheimer's disease. To achieve this, we determined the change of the MAPK pathway, secretase activity, and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M. Based on these results, we concluded that, i) CMV/GFP-hSelM Tg rats showed a high activity level of antioxidant enzyme in the brain tissues, ii) in response to selenium treatment, the ERK signaling pathway was significantly increased in Tg rats, but did not change in wild-type rats, iii) the activation of the ERK pathway by selenium treatment and SelM overexpression induced the inhibition of the alpha/gamma-secretase activity related to the protection of Abeta-42 production, iv) the activation of the ERK pathway by selenium treatment and SelM overexpression inhibited the phosphorylation in several sites of Tau protein. Therefore, these results provide strong evidence that selenium treatment and SelM activate the ERK pathway to attenuate alpha/gamma-secretase-mediated proteolysis and Tau phosphorylation to protect brain function.
...
PMID:ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M. 1951 40

In this study, we provide evidence that the muscarinic M1 receptor targets NF-E2-related factor-2 (Nrf2), a transcription factor that regulates the expression of genes containing antioxidant response elements (AREs) in their promoters and that collectively constitute the phase II antioxidant response. In hippocampal primary and cerebellar granule neuron cultures expressing endogenous M1 receptor, carbachol increased the levels of a prototypical phase II antioxidant enzyme, heme oxygenase-1. Moreover, in a heterologous system, based on lentiviral expression of M1 receptor in PC12 pheochromocytoma cells, we found that M1 increased total and nuclear Nrf2 protein levels and heme oxygenase-1 messenger RNA and protein levels. Luciferase reporter constructs for AREs and the use of two inhibitors of protein kinase C (PKC), chelerythrine and 2-aminoethyl diphenylborinate, or transfection with relevant expression vectors allowed us to identify Galphaq, phospholipase C-beta and the classical PKC-gamma isoenzyme, as responsible for the regulation of Nrf2. A PKC-insensitive Nrf2S40A single-point mutant partially channeled M1 signaling to AREs, therefore suggesting the participation of additional intermediates. Inhibition of glycogen synthase kinase-3beta (GSK-3beta) augmented M1-dependent activation of AREs while a PKC-insensitive mutant of GSK-3beta (GSK-3beta-Delta9) blocked this effect and prevented M1-induced accumulation of Nrf2 in the nucleus. Our results demonstrate a previously unidentified role of the Galphaq/phospholipase C-beta/PKC/GSK-3beta axis in regulation of Nrf2 by M1. Such role provides additional conceptual support for the use of cholinemimetics in the treatment of pathologies that, like Alzheimer's disease, require a reinforcement of the cell antioxidant capacity.
...
PMID:The muscarinic M1 receptor activates Nrf2 through a signaling cascade that involves protein kinase C and inhibition of GSK-3beta: connecting neurotransmission with neuroprotection. 1955 56

Numerous studies characterizing the function of glutathione peroxidase 4 (GPx4) have demonstrated that this selenoenzyme is protective against oxidative stress. Herein, we characterized the function of this protein by targeting GPx4 downregulation using RNA interference. Partial knockdown of GPx4 levels resulted in growth retardation and morphological changes. Surprisingly, GPx4 knockdown cells showed virtually unchanged levels of intracellular ROS, yet highly increased levels of oxidized lipid by-products. GPx1, another glutathione peroxidase and a major cellular peroxide scavenging enzyme, did not rescue GPx4-deficient cells and did not reduce lipid peroxide levels. The data established an essential role of GPx4 in protecting cells against lipid hydroperoxide damage, yet a limited role as a general antioxidant enzyme. As oxidized lipid hydroperoxides are a characteristic of neurodegenerative diseases, we analyzed brain tissues of mice suffering from a model of Alzheimer's disease and found that oxidized lipid by-products were enriched, and expression of both GPx4 and guanine-rich sequence-binding factor, which is known to control GPx4 synthesis, was downregulated. Brain tissue from an Alzheimer's diseased human also manifested enhanced levels of one of the oxidized lipid by-products, 4-hydroxynonenal. These data suggest a role of GPx4 in neurodegenerative diseases through its function in removal of lipid hydroperoxides.
...
PMID:Delineating the role of glutathione peroxidase 4 in protecting cells against lipid hydroperoxide damage and in Alzheimer's disease. 1976 63

Soluble oligomeric amyloid beta (oAbeta) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer's disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAbeta1-42 neurotoxicity is not fully understood. Here, we showed that oAbeta but not fibrillar Abeta was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAbeta1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAbeta1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia to promote neuroprotection. Moreover, intracerebroventricular administration of CpG ameliorated both the cognitive impairments induced by oAbeta1-42 and the impairment of associative learning in Tg2576 mouse model of AD. We propose that CpG may be an effective therapeutic strategy for limiting oAbeta1-42 neurotoxicity in AD.
...
PMID:Microglia activated with the toll-like receptor 9 ligand CpG attenuate oligomeric amyloid {beta} neurotoxicity in in vitro and in vivo models of Alzheimer's disease. 1983 64

Oxidative stress is a key factor involved in the development and progression of Alzheimer disease (AD), and it is well documented that free radical oxidative damage, particularly of neuronal lipids, proteins, nucleic acids, and sugars, is extensive in brains of AD patients. The complex chemistry of peroxynitrite has been the subject of intense study and is now evident that there are two principal pathways for protein modification: the first one involves homolytic hydroxyl radical-like chemistry that results in protein-based carbonyls and the second involves electrophilic nitration of vulnerable side chains, in particular the electron-rich aromatic rings of Tyr and Trp. In the presence of buffering bicarbonate, peroxynitrite forms a CO(2) adduct, which augments its reactivity. Formation of 3-nitrotyrosine by this route has become the classical protein marker specifically for the presence of peroxynitrite. Protein-based carbonyls can be detected by two methods: (i) derivatization with 2,4-dinitrophenylhydrazine (DNPH) and detection of the protein-bound hydrazones using an enzyme-linked anti-2,4-dinitrophenyl antibody and (ii) derivatization with biotin-hydrazide and detection of the protein-bound acyl hydrazone with enzyme-linked avidin or streptavidin. Glycation of proteins by reducing sugars (Maillard reaction) results in a profile of time-dependent adduct evolution rendering susceptibility to oxidative elaboration. In addition, oxidative stress can result in oxidized sugar derivatives which can subsequently modify protein through a process known as glycoxidation. Of more general importance, oxidative stress results in lipid peroxidation and the production of a range of electrophilic and mostly bifunctional aldehydes that modify numerous proteins. The more important protein modifications are referred to as advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). Protein modification can result in both non-cross-link and cross-link AGEs and ALEs, the latter arising from the potential bifunctional reactivity, such as that of the lipid-derived modifiers 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA). Oxidative damage to nucleic acids results in base modification, substitutions, and deletions. Among the most common modifications, 8-hydroxyguanosine (8OHG) is considered a signature of oxidative damage to nucleic acid.Cells are not passive to increased oxygen radical production but rather upregulate protective responses. In neurodegenerative diseases, heme oxygenase-1 (HO-1) induction is coincident with the formation of neurofibrillary tangles. This enzyme that converts heme, a prooxidant, to biliverdin/bilirubin (antioxidants) and free iron has been considered an antioxidant enzyme. But seen in the context of arresting apoptosis, HO-1 and tau may play a role in maintaining the neurons free from the apoptotic signal (cytochrome c), since tau has strong iron-binding sites. Given the importance of iron as a catalyst for the generation of reactive oxygen species, changes in proteins associated with iron homeostasis can be used as an index of cellular responses. One such class of proteins is the iron regulatory proteins (IRPs) that respond to cellular iron concentrations by regulating the translation of proteins involved in iron uptake, storage, and utilization. Therefore, IRPs are considered to be the central control components of cellular iron concentration.
...
PMID:Detection and localization of markers of oxidative stress by in situ methods: application in the study of Alzheimer disease. 2001 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---