Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inflammatory cytokines have been shown to upregulate secretion of the antioxidant enzyme extracellular superoxide dismutase (EC-SOD) in dermal fibroblasts and, in other cells, to stimulate production of nitric oxide (.NO). Because superoxide rapidly scavenges .NO, forming the injurious peroxynitrite anion (OONO-), we hypothesize that stimulated cells upregulate EC-SOD expression concurrently with .NO release. To test for coregulation of EC-SOD and .NO within the same cell, the timing of inducible nitric oxide synthase (iNOS) and EC-SOD transcription was measured after exposure of a rate type II pneumocyte analog, the L2 cell line, to a combination of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Upregulation of iNOS and EC-SOD transcription occurred after 6 h of exposure, and transcription of both genes was linked by activation of the transcription factor nuclear factor-kappa B. Both EC-SOD and iNOS were elevated in rat lung homogenates 24 h after intratracheal instillation with IFN-gamma and TNF-alpha. The observation that EC-SOD and iNOS are temporally coregulated after cytokine exposure suggests the possibility of a critical mechanism by which cells might protect .NO and avoid the formation of OONO- during inflammation.
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PMID:Extracellular superoxide dismutase is upregulated with inducible nitric oxide synthase after NF-kappa B activation. 937 27

15-deoxy-Delta(12,14)-PGJ(2), a cyclopentenone derivative of PGD(2), was recently reported [Petrova et al., Proc. Natl. Acad. Sci. USA 96 (1999) 4668-4673] to suppress inducible nitric oxide synthase (iNOS) production in microglia and mixed glial cultures stimulated with lipopolysaccharide (LPS). We report here that in addition to suppressing iNOS production, 15d-PGJ(2) also decreases the production of tumor necrosis factor alpha (TNFalpha), interleukin-1 beta (IL-1beta) and cyclooxygenase-2 (COX-2) in LPS-stimulated BV-2 microglial cells, thereby acting as a general inhibitor of microglial activation. Concomitantly, 15d-PGJ(2) itself up-regulates the production of the antioxidant enzyme heme oxygenase-1 (HO-1) and increases intracellular total glutathione levels. To test if increased HO-1 levels were involved in the ability of 15d-PGJ(2) to block microglial activation, we used a HO-1 inhibitor that could block the activity of HO-1. The presence of the HO-1 inhibitor did not alter the 15d-PGJ(2)-induced inhibition of LPS-stimulated iNOS and TNFalpha protein levels, and led to only a partial reduction in the protection offered by 15d-PGJ(2) against LPS-induced nitrite production. These results suggest that HO-1 upregulation by 15d-PGJ(2) is not the primary pathway responsible for the anti-inflammatory action of 15d-PGJ(2) in microglial cells.
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PMID:Cyclopentenone prostaglandin 15-deoxy-Delta(12,14)-prostaglandin J(2) acts as a general inhibitor of inflammatory responses in activated BV-2 microglial cells. 1083 4

Oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis. Inflammatory genes including inducible nitric oxide synthase (iNOS) may be regulated by oxidant-sensitive transcription factor, nuclear factor-kappaB (NF-kappaB). iNOS induction has been related to gastric apoptosis. We studied the role of NF-kappaB on iNOS expression and apoptosis in H. pylori-stimulated gastric epithelial AGS cells. AGS cells were treated with antisense oligonucleotide (AS ODN) for NF-kappaB subunit p50, an antioxidant enzyme catalase, an inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC), iNOS inhibitors N(G)-nitro-L-arginine-methyl ester (L-NAME) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT), a peroxynitrite donor SIN-1, and a nitric oxide donor NOC-18 in the presence or absence of H. pylori. H. pylori induced cytotocixity time- and dose-dependently, which occurred with induction in iNOS expression and nitrite production. SIN-1 and NOC-18 induced dose-dependent cytotoxicity in AGS cells. Catalase, PDTC, L-NAME, and AMT prevented H. pylori-induced cytotoxicity and apoptosis. It was related to their inhibition on iNOS expression and nitrite production. The cells treated with AS ODN had low levels of p50 and NF-kappaB and inhibited H. pylori-induced cytotoxicity, apoptosis, iNOS expression, and nitrite production. In conclusion, NF-kappaB plays a novel role in iNOS expression and apoptosis in H. pylori-infected gastric epithelial cells.
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PMID:NF-kappaB, inducible nitric oxide synthase and apoptosis by Helicobacter pylori infection. 1146 73

Many individuals with cardiovascular diseases undergo periodic exercise conditioning with or with out medication. Therefore, this study investigated the interaction of exercise training and chronic nitric oxide synthase (NOS) inhibitor (Nitro-L-Arginine Methyl Ester, L-NAME) treatment on blood pressure and its correlation with aortic nitric oxide (NO), antioxidant defense system and oxidative stress parameters in rats. Fisher 344 rats were divided into four groups: (1) sedentary control, (2) exercise training (ET) for 8 weeks, (3) L-NAME (10 mg/kg, subcutaneous for 8 weeks) and (4) ET + L-NAME. Blood pressure (BP) was monitored weekly for 8 weeks with tail-cuff method. The animals were sacrificed 24 h after last treatments and thoracic aortic rings were isolated and analyzed. Exercise conditioning resulted in a significant increase in respiratory exchange ratio (RER), aortic NO production, NO synthase activity and inducible iNOS protein expression. Training significantly enhanced aortic GSH levels, GSH/GSSG ratio and up-regulation of aortic CuZn-SOD, Mn-SOD, catalase (CAT), glutathione peroxidase (GSH-Px) activity and protein expression and significantly decreased aortic lipid peroxidation. Chronic L-NAME administration resulted in a significant depletion of aortic NO, NOS activity, endothelial (eNOS) and iNOS protein expression, GSH level, GSH/GSSG ratio, down-regulation of aortic antioxidant enzyme activities and protein expressions. Aortic xanthine oxidase (XO) activity significantly increased with increased lipid peroxidation and protein oxidation after L-NAME administration. The biochemical changes were accompanied by increased in BP. Interaction of training and chronic NOS inhibitor treatment resulted in normalization of BP and aortic antioxidant enzyme activity and protein expression, up-regulation of aortic GSH/GSSG ratio, NO levels, Mn-SOD protein expression, depletion of GSSG, protein oxidation and lipid peroxidation. The data suggest that training attenuated the oxidative injury caused by chronic NOS inhibitor treatment by up-regulating the NO and antioxidant systems and lowering the BP in rats.
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PMID:Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. 1195 54

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.
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PMID:Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease. 1551 90

The aim of this study was to investigate the role of nitric oxide (NO) in hepatic ischemia-reperfusion (I/R) injury in rats. Immunohistochemistry was used to examine the protein expression of endothelial and inducible nitric oxide synthases (eNOS, iNOS) and nitrotyrosine after I/R challenges to the liver, and blood levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), hydroxyl radical and NO were measured before ischemia and after reperfusion. Ischemia was induced by occlusion of the common hepatic artery and portal vein for 40 min, followed by reperfusion for 90 min. Reperfusion of the liver induced a significant increase in the blood concentrations of AST, ALT, LDH (n = 8; P < 0.001), hydroxyl radical (n = 8; P < 0.001) and NO (n = 8; P < 0.01). The eNOS, iNOS, nitrotyrosine, SOD1 and SOD2 protein expression was also found to increase significantly after reperfusion (n = 3). Administration of the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (n = 8) had a protective effect on the I/R-related injury, but the NO donor L-arginine (L-Arg) (n = 8) potentiated the damage caused by I/R. These results suggest that reperfusion of the liver induces expression of NOS, which is related to the elevation of blood NO. The increase in hydroxyl radical concentration was accompanied by an increase in antioxidant enzyme expression (SOD1 and SOD2), and an increase in nitrotyrosine expression was also observed, reflecting the increased production of NO and oxygen radicals. We concluded from the protective effect of L-NAME and the potentiation by L-Arg that NOS expression and increases in NO and hydroxyl radical production have deleterious effects on the response to I/R in the liver.
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PMID:Ischemia and reperfusion of liver induces eNOS and iNOS expression: effects of a NO donor and NOS inhibitor. 1561 29

The Brucella genus is able to cause chronic infection in a wide range of mammals including humans. Oxidative events, lipid peroxidation and inflammatory response against Brucella infection have not yet been well elucidated in vivo. We have investigated oxidative/antioxidative status and nitric oxide production in plasma, brain, liver and spleen during a 60 day period of B. melitensis infection in a rat model. In addition, inducible nitric oxide synthase (iNOS), IL-10, IL-12, IFN-gamma and TNF-alpha mRNA transcriptions were analyzed by semiquantitative reverse transcriptase PCR (RT-PCR) in brain samples. Animals were infected with B. melitensis and sacrificed at 7th, 15th, 30th, 45th and 60th day of post-inoculation. Malondialdehyde (MDA), as an indicator of lipid peroxidation, and nitric oxide (NO) concentrations were significantly increased after Brucella inoculation and began to decline to basal levels from 45th day in plasma, liver and spleen. However, iNOS transcription was not induced during the infection period in brains. In contrast, MDA level was increased in brain during the late phase of infection without any change in NO production. The infection did not alter the antioxidant enzyme activities in the tissues; although significantly increased catalase activity was observed between days 30 and 45 in the liver. Transcription analyses demonstrated that IL-10, IL-12 and IFN-gamma mRNA level were not induced in the brain. Only TNF-alpha mRNA was weakly up-regulated in brain 30 days after pathogen inoculation. The results obtained in this study demonstrate that B. melitensis induces lipid peroxidation and NO production in the liver and spleen in the early days of infection, but that these levels subsequently decline. Moreover, Brucella does not appear to induce antioxidant enzyme activities and inflammation during two months of infection. However, the pathogen does stimulate cerebral lipid peroxidation in the late phase of infection without causing significant inflammation.
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PMID:Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection. 1681 May 61

Adriamycin (ADR), a potent anti-tumor agent, produces reactive oxygen species (ROS) in cardiac tissue. Treatment with ADR is dose-limited by cardiotoxicity. However, the effect of ADR in the other tissues, including the brain, is unclear because ADR does not pass the blood-brain barrier. Some cancer patients receiving ADR treatment develop a transient memory loss, inability to handle complex tasks etc., often referred to by patients as chemobrain. We previously demonstrated that ADR causes CNS toxicity, in part, via systemic release of cytokines and subsequent generation of reactive oxygen and nitrogen species (RONS) in the brain. Here, we demonstrate that treatment with ADR led to an increased circulating level of tumor necrosis factor-alpha in wild-type mice and in mice deficient in the inducible form of nitric oxide (iNOSKO). However, the decline in mitochondrial respiration and mitochondrial protein nitration after ADR treatment was observed only in wild-type mice, not in the iNOSKO mice. Importantly, the activity of a major mitochondrial antioxidant enzyme, manganese superoxide dismutase (MnSOD), was reduced and the protein was nitrated. Together, these results suggest that NO is an important mediator, coupling the effect of ADR with cytokine production and subsequent activation of iNOS expression. We also identified the mitochondrion as an important target of ADR-induced NO-mediated CNS injury.
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PMID:Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain. 1722 39

The aim was to study the effects of a scuba diving session on the lymphocyte antioxidant system, NO synthesis, the capability to produce reactive oxygen species and the antioxidant response in neutrophils. For that purpose seven male divers performed an immersion at a depth of 40 m for 25 min. The same parameters were measured after an hyperbaric oxygen (HBO) treatment at resting conditions in a hyperbaric chamber. Lymphocyte H2O2 production rose after diving and after HBO treatment. Glutathione peroxidase (GPx) and catalase activities increased after diving in lymphocytes, while after HBO exposure only increased GPx activity. Lymphocyte HO-1 mRNA expression increased after diving and after HBO exposure, while iNOS levels and nitrite levels significantly increased after diving. The hyperoxia associated to scuba diving leads to a condition of oxidative stress with increased lymphocyte H2O2 production, HO-1 expression, NO synthesis and antioxidant enzyme adaptations in order to avoid oxidative damage.
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PMID:Scuba diving enhances endogenous antioxidant defenses in lymphocytes and neutrophils. 1736 55

We have previously demonstrated that induction of apoptosis was observed in the smooth chorion trophoblast cells of human fetal membranes prepared at term, and that apoptosis progressed rapidly during in vitro incubation of the tissues. Furthermore, we identified the contribution of ROS production system (e.g., oxidant enzymes, such as iNOS and Cox-2) to the apoptosis induction in the chorion cells, suggesting an important role of the two inducible enzymes in the induction process. In this study, we examined the role of ROS elimination system (e.g., antioxidant enzymes, such as glutathione peroxidase (GPx) and catalase) in the apoptosis induction of the chorion cells, since the apoptosis induction by oxidative stress is a result of imbalance between production and elimination of ROS. Treatment of chorion and amnion cells with mercaptosuccinic acid (MS, GPx inhibitor) and 3-amino-1,2,4-triazole (ATZ, catalase inhibitor) resulted in an inhibition of GPx and catalase activity, respectively. Furthermore, incubation with MS alone induced apoptosis in the chorion cells and apoptosis level was enhanced by the addition of ATZ, while ATZ alone hardly induced apoptosis in the chorion cells. However, none of these reagents induced apoptosis in the amnion cells. Moreover, an increase of the level of hemeoxygenase-1 gene expression was observed only in the amnion cells when both antioxidant enzyme activities were suppressed. Therefore, we concluded that GPx played a more critical role than catalase in the control of the apoptosis induction of the chorion cells, suggesting that the threshold levels of stress tolerance in the chorion cells are much lower than those in the amnion cells.
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PMID:Imbalance between ROS production and elimination results in apoptosis induction in primary smooth chorion trophoblast cells prepared from human fetal membrane tissues. 1823 33


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