Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species are thought to play an important role in some bowel diseases. In order to evaluate the participation of nitric oxide and superoxide in such diseases, we examined the expression of nitric oxide synthase (NOS) and superoxide dismutase (SOD) as well as their activities in whole excised colons of rats with colitis induced by intralumenal administration of 2,4,6-trinitrobenzenesulfonic acid. A marked increase in the inducible form of NOS mRNA was detected and NOS activity was coincidentally augmented in the group administered unbuffered TNBS (pH 1.0), in which severe inflammation was revealed by microscopic examination and myeloperoxidase activity of invading neutrophils in the tissues. The levels of the Mn- and Cu,Zn-SOD proteins as well as SOD activity were suppressed, although expression of the Mn-SOD mRNA was enhanced in colitis tissues. The elevation of NOS activity and the suppression of SOD activity occurred concomitantly at the stage of severe inflammation. This would increase peroxynitrite formation from superoxide and nitric oxide and enhance the tissue damage in experimental colitis.
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PMID:Induction of nitric oxide synthase and concomitant suppression of superoxide dismutases in experimental colitis in rats. 750 57

A simple method in mice was established to screen anti-ischemic compounds. Thirteen times binding of rubber ring (1 x 1 mm, d = 42 mm) for 4.5 hrs, swelled the paws of 60% mice applied and 14 times binding swelled only of 5% mice. Critically reversible limit lay between these conditions. "All or none" rule dominated the paw swelling perhaps due to different endogenous anti-oxidants' levels of individual mice. Determination of paw reversibility at 90 min of recirculation, was proved to be suitable. Swollen paws at this time returned normal and the paws with no-reflow dropped out by muscle necrosis after several days. Intravenous (i.v.) bovine Cu, Zn-SOD and bacterial Mn-SOD (3-10 x 10(4) U/kg) or liposomal Cu, Zn-SOD (0.3-3 x 10(4) U/kg) were protective (35-50%) by 14 times binding. Allopurinol (10-100 mg/kg) and D-mannitol (3-30 mg/kg) was effective (25-55%). Catalase (i.v., up to 10(5) U/kg) showed little protection, but local injection of 100 U/kg resulted in 50% protection. Glutathione (30 mg/kg) was suppressive only by local injection suggesting the importance of administration route. Desferal, heparin and nitric oxide synthesis inhibitor showed some protection, but indomethacin, mepyramine, ascorbate, vitamin E and dexamethasone were without effect. Excess dosing of all anti-oxidants tested, dramatically decreased their effects demanding caution for therapeutic trials.
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PMID:Superoxide dismutases and anti-oxidants protected mice from no-reflow and necrotic damage induced by ischemia. 831 25

The cytokine IL-1 beta has previously been demonstrated to induce the expression of the stress genes iNOS, hsp70, heme oxygenase and Mn-SOD in rat pancreatic islets in vitro. The aim of this study was to determine whether the IL-1 beta-induced effects are specific for the insulin producing beta-cell, or whether other islet cells, such as the glucagon-producing alpha-cell, respond to IL-1 beta addition. Purified rat alpha- and beta-cell suspensions were obtained by fluorescence-activated cell sorting and incubated with or without IL-1 beta (25 U/ml) for 24 h. The alpha- and beta-cell contents of hsp70, heme oxygenase and Mn-SOD and medium nitrite levels were determined. It was found that IL-1 beta exposure induced the production of nitric oxide in beta-cells, but not in alpha-cells. Moreover, the expression of hsp70, heme oxygenase and Mn-SOD was also induced in beta-cells, but not in alpha-cells. There were no detectable levels of hsp70 in alpha-cells. It is concluded that the stress gene response following IL-1 beta exposure is markedly different in alpha- and beta-cells. This finding may be of importance for the understanding of the autoimmune destruction of beta-cells in insulin-dependent diabetes mellitus.
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PMID:Interleukin-1 beta induces the expression of hsp70, heme oxygenase and Mn-SOD in FACS-purified rat islet beta-cells, but not in alpha-cells. 871 14

Asthma-like symptoms were induced in mice by repeated intratracheal instillation of diesel exhaust particles. Nitric oxide synthase (NOS) and superoxide dismutase (SOD) in airways were studied with immunocytochemical methods, and the role of nitric oxide was examined with the NOS inhibitor L-NMMA. Diesel exhaust particles increased the staining of cNOS in airway epithelial cells by an anti-cNOS antibody. Macrophages in the mucous membrane were stained clearly, but an anti-iNOS antibody did not stain airway epithelial cells. Diesel exhaust particles caused a 4-fold increase in the total number of macrophages, neutrophils, eosinophils, and lymphocytes in bronchoalveolar lavage fluid. Diesel exhaust particles decreased the staining of Cu, Zn-SOD, and Mn-SOD in epithelial cells by their respective anti-SOD antibodies. Diesel exhaust particles doubled the concentration of nitric oxide in exhaled air. These particles increased respiratory resistance, and this increase was suppressed by pretreatment with the NOS inhibitor L-NMMA. These results suggest that diesel exhaust particles can decrease the scavenging of O2- in airways, which may increase hyperresponsiveness. In mice exposed to diesel exhaust particles, the increase in NOS staining in airway epithelium, the increase in the nitric oxide concentration in exhaled air, and the decrease in respiratory resistance caused by L-NMMA indicate that nitric oxide may increase airway hyperresponsiveness.
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PMID:[Role of nitric oxide in asthma-like symptoms induced by diesel exhaust particles in mice]. 875 9

To understand the possible mechanism of nitric oxide (NO)-mediated cytotoxicity, we investigated the effect of NO on the endogenous antioxidant enzymes (AOEs) catalase, glutathione peroxidase (GPX), and CuZn- and Mn-superoxide dismutases (SODs) in rat C6 glial cells under conditions in which these cells expressed oligodendrocyte-like properties as evidenced by the expression of 2',3'-cyclic-nucleotide 3'-phosphohydrolase. The 24-h treatment with S-nitroso-N-acetylpenicillamine (SNAP), a NO donor, decreased the activities and the protein levels of catalase, GPX, and Mn-SOD in a dose-dependent manner. Alternatively, the activity and the protein level of CuZn-SOD were increased. 2-Phenyl-4,4, 5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a NO scavenger, blocked the effect of SNAP. Moreover, the treatment of C6 cells with sodium nitroprusside, another NO donor, or with a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), which induce excessive production of NO, also significantly modulated the AOE activities in a manner similar to that seen with SNAP treatment. The compounds/enzymes that inhibit the production of NO (e.g., N-nitro-L-arginine methyl ester hydrochloride, arginase, and PTIO) blocked the effects of LPS and IFN-gamma on the activities of AOEs. Treatment with SNAP and a combination of LPS and IFN-gamma also modulated the mRNA levels of AOEs, parallel to the changes in their protein levels and activities, except for Mn-SOD where the combination of LPS and IFN-gamma markedly stimulated the mRNA expression. In spite of the stimulation of mRNA level, LPS and IFN-gamma significantly inhibited the activity of Mn-SOD within the first 24 h of incubation; however, Mn-SOD activity gradually increased with the increase in time of incubation. These results suggest that alterations in the status of AOEs by NO may be the basis of NO-induced cytotoxicity in disease states associated with excessive NO production.
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PMID:Modulation of endogenous antioxidant enzymes by nitric oxide in rat C6 glial cells. 910 15

The production of reactive nitrogen intermediates (RNI) by macrophages is critical to host defence, particularly for exerting the bactericidal and tumoricidal properties. Nitric oxide (NO) were measured in the peripheral blood-derived monocytes/macrophages of normal and leprosy patients (BT/TT and BL/LL) in the presence and absence of 'tuftsin' as a function of in vitro culture age (on 1, 3, 7 days). Macrophages from both groups of leprosy patients were able to produce NO during the unstimulated state but only BL/LL macrophages could be activated by tuftsin to produce significantly high levels of NO. This increase was highest on day 1, then gradually decreased with in vitro culture age. Surprisingly, tuftsin was unable to enhance the NO production in normal macrophages above the basal level. Further, normal and BT/TT macrophages had only Cu-Zn derived superoxide dismutase (SOD) activity whereas BL/LL cultures has Cu-Zn and Mn derived SOD activity. These studies indicate that in BL/LL cultures: a, apart from tuftsin, some additional signal is required to activate nitric oxide synthase (NOS) gene for NO production; and b, Mn-SOD produced by Mycobacterium leprae is playing a defensive role against toxic-free radicals. The final outcome of this mechanism is the survival of M. leprae inside the macrophages.
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PMID:Release of reactive nitrogen intermediates from the peripheral blood-derived monocytes/macrophages of leprosy patients stimulated in vitro by tuftsin. 912 27

The normal pancreatic beta-cell population exhibits intercellular differences in its responsiveness to glucose. This cellular heterogeneity allows glucose to regulate, in a dose-dependent manner, total rates of insulin synthesis and release. It may also predispose to intercellular differences in susceptibility to dysregulating agents. The present study examines whether this is the case for interleukin 1beta (IL-1beta), which is known to suppress glucose-induced insulin synthesis and release. The effects of the cytokine were compared on beta-cell subpopulations with, respectively, high and low sensitivity to glucose. These subpopulations were separated on the basis of differences in the cellular metabolic responsiveness to an intermediate glucose concentration (7.5 mmol/liter) and then cultured for 20 h at 5 or 20 mmol/liter with or without IL-1beta. The suppressive action of IL-1beta (0.1 ng/ml) occurred predominantly in glucose-activated beta cells, reducing their high rates of insulin synthesis and release by more than 80%. Glucose-unresponsive cells became subject to a similar inhibition after their activation during culture at 20 mmol/liter glucose. On the other hand, IL-1beta induced or enhanced the expression of several noninsulin proteins in both subpopulations. The IL-1beta-stimulated expression of inducible nitric oxide synthase (iNOS) and heat shock protein 70 was more marked in the glucose-responsive subpopulation; that of heme oxygenase and Mn superoxide dismutase was comparable in the two subpopulations. Exposure to IL-1beta resulted in 10-fold higher medium nitrite levels in both subpopulations; this effect was prevented by the iNOS blocker, N(G)-methyl-L-arginine, which also prevented the IL-1beta-induced suppression in the glucose-responsive subpopulation. This study demonstrates that the cellular heterogeneity in glucose responsiveness predisposes to intercellular differences in the IL-1-induced suppression of insulin synthesis and release. While the cytokine induces the expression of noninsulin proteins such as iNOS in both glucose responsive and unresponsive cells, the subsequent nitric oxide production appears to predominantly affect glucose-stimulated functions in the glucose-activated cells.
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PMID:Intercellular differences in interleukin 1beta-induced suppression of insulin synthesis and stimulation of noninsulin protein synthesis by rat pancreatic beta-cells. 952 32

To examine the cellular distribution of radical scavenging enzymes in glia, in comparison to that in neurons and their behaviour during excitotoxically induced neurodegenerative processes, protein levels and the cellular localization of cytosolic and mitochondrial superoxide dismutase (Cu/Zn- and Mn-SOD) were investigated in the rat brain undergoing quinolinic acid (Quin)-induced neurodegeneration. Evidence for the specificity of the applied antibodies to detect immunocytochemically these SOD isoforms was obtained from electron microscopy and Western blotting. In control striatum Mn-SOD was clearly confined to neurons, whereas Cu/Zn-SOD was found, rather delicately, only in astrocytes. Microglia failed to stain with antibodies to both SOD isoforms. Quin application resulted in an initial formation of oxygen and nitrogen radicals as determined by the decline in the ratio of ascorbic to dehydroascorbic acid and by increased levels of nitrated proteins, an indicator for elevated peroxynitrite formation. Morphologically, massive neuronal damage was seen in parallel. Astroglia remained intact but showed initially decreased glutamine synthetase activities. The levels of Mn-SOD protein increased 2-fold 24 h after Quin injection (Western blotting) and declined only slowly over the time period considered (10 days). Cu/Zn-SOD levels increased only 1.3-fold. Immunocytochemical studies revealed that the increase in Mn-SOD is confined to neurons, whereas that of Cu/Zn-SOD was observed only in astroglial cells. Quiescent microglial cells were, as a rule, free of immunocytochemically detectable SOD, whereas in activated microglia a few Mn-SOD immunolabeled mitochondria occurred. Our results suggest a differential protective response in the Quin lesioned striatum in that Mn-SOD is upregulated in neurons and Cu/Zn-SOD in astroglia. Both SOD-isoforms are assumed to be induced to prevent oxidative and nitric oxide/peroxynitrite-mediated damage. In the border zone of the lesion core this strategy may contribute to resist the noxious stimulus.
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PMID:Differential expression of superoxide dismutase isoforms in neuronal and glial compartments in the course of excitotoxically mediated neurodegeneration: relation to oxidative and nitrergic stress. 967 59

We previously demonstrated that chronic intratracheal instillation of diesel exhaust particles (DEP) induces airway inflammation and hyperresponsiveness in the mouse, and that these effects were partially reversed by the administration of superoxide dismutase (SOD). In the present study, we have investigated the involvement of superoxide in DEP-induced airway response by analyzing the localization and activity of two enzymes: (1) a superoxide producer, NADPH cytochrome P-450 reductase (P-450 reductase), and (2) a superoxide scavenger, SOD, in the lungs of the exposed mice and controls. P-450 reductase was detected mainly in ciliated cells and clara cells: its activity was increased by the repeated intratracheal instillation of DEP. While CuZn-SOD and Mn-SOD were also present in the airway epithelium, their activity was significantly decreased following DEP instillation. Exposure to DEP doubled the level of nitric oxide (NO) in the exhaled air. DEP exposure also increased the level of constitutive NO synthase (cNOS) in the airway epithelium and inducible NO synthase (iNOS) in the macrophages. Pretreatment with N-G-monomethyl L-arginine, a nonspecific inhibitor of NO synthase, significantly reduced the airway hyperresponsiveness induced by DEP. These results indicate that superoxide and NO may each contribute to the airway inflammation and hyperresponsiveness induced by the repeated intratracheal instillation of DEP in mice.
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PMID:Involvement of superoxide and nitric oxide on airway inflammation and hyperresponsiveness induced by diesel exhaust particles in mice. 980 Oct 62

S-Nitrosothiols formed from the nitric oxide (NO)-dependent S-nitrosation of thiol-containing proteins and peptides such as albumin and glutathione (GSH) have been implicated in the transport, storage, and metabolism of NO in vivo. Recent data suggest that certain transition metals enhance the decomposition of S-nitrosothiols in vitro. The objective of this study was to determine what effect Cu, Zn superoxide dismutase (CuZn-SOD) has on the stability of certain S-nitrosothiols such as S-nitrosoglutathione (GSNO) in vitro. We found that CuZn-SOD (20 microM) but not Mn-SOD in the presence of GSH catalyzed the decomposition of GSNO with a Vmax of 6.7 +/- 0.4 microM/min and a Km of 5.6 +/- 0.5 microM at 37 degreesC. Increasing GSH concentrations with respect to CuZn-SOD resulted in complete decomposition of GSNO at concentrations of GSH:SOD of 2:1. Increasing GSH concentrations further from 0.1 to 10 mM resulted in a concentration-dependent attenuation in GSNO decomposition suggesting that SOD-catalyzed decomposition of GSNO would be maximal at concentrations of GSH known to be present in extracellular fluids (e.g., plasma). The decomposition of GSNO by CuZn-SOD resulted in the sustained production of NO. We propose that GSH reduces enzyme-associated Cu2+ to Cu1+ which mediates the reductive decomposition of the S-nitrosothiol to yield free NO. We conclude that CuZn-SOD may represent an important physiological modulator of steady-state concentrations of low-molecular-weight S-nitrosothiols in vivo.
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PMID:Effect of superoxide dismutase on the stability of S-nitrosothiols. 988 63


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