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)

Seed germination is an important developmental switch when quiescent seed cells initiate oxidative phosphorylation for further development and differentiation. During early imbibition of soybean seeds (Glycine max L. cv. Weber), a superoxide dismutase (SOD) activity peak was observed, in embryonic axes, after 6 h imbibition. Peroxidase activities, including catalase, were significantly increased after 12 h inhibition and during germination phase III. Catalase was the most efficient enzyme in catabolizing H2O2 in embryonic axes. When stored at 42 degrees C and 100% relative humidity, seeds were stressed and lost their viability in a time-dependent manner. A significant increase in the Cu, Zn-superoxide-dismutase activity, and to a lesser extent, Mn superoxide dismutase activity was observed during germination in low-viability (stressed) seeds as compared to high-viability (unstressed) seeds. Northern blot analysis confirmed that superoxide dismutase induction resulted from an accumulation of its transcripts in response to the production of O2-. The induction of catalase did not occur in low-viability seeds, resulting in dramatic accumulation of H2O2. Using capillary electrophoresis, HPLC and NMR we found that the endogenous cytokinin, zeatin riboside, was present in large quantities in the high-viability seeds, but it was oxidized into adenine in the low-viability seeds. In vitro superoxide anion could also oxidize the cytokinin. Zeatin riboside, but not adenine, was found to act as a scavenger of superoxide anions and may help to maintain seed viability by detoxifying reactive oxygen species. Germination of stressed seeds was partially restored by the addition of exogenous cytokinin (zeatin riboside). Protection against oxidative stress by cytokinin seemed to be a general phenomenon, as Escherichia coli cells were also protected against superoxide stress in the presence of cytokinin.
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PMID:Accumulation of reactive oxygen species and oxidation of cytokinin in germinating soybean seeds. 752 1

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.
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PMID:Regulation of antioxidant enzymes in lung after oxidant injury. 752 4

O2- oxidizes the [4Fe-4S] clusters of dehydratases, such as aconitase, causing-inactivation and release of Fe(II), which may then reduce H2O2 to OH- +OH.. SODs inhibit such HO. production by scavengingO2-, but Cu, ZnSODs, by virtue of a nonspecific peroxidase activity, may peroxidize spin trapping agents and thus give the appearance of catalyzing OH. production from H2O2. There is a glycosylated, tetrameric Cu, ZnSOD in the extracellular space that binds to acidic glycosamino-glycans. It minimizes the reaction of O2- with NO. E. coli, and other gram negative microorganisms, contain a periplasmic Cu, ZnSOD that may serve to protect against extracellular O2-. Mn(III) complexes of multidentate macrocyclic nitrogenous ligands catalyze the dismutation of O2- and are being explored as potential pharmaceutical agents. SOD-null mutants have been prepared to reveal the biological effects of O2-. SodA, sodB E. coli exhibit dioxygen-dependent auxotrophies and enhanced mutagenesis, reflecting O2(-)-sensitive biosynthetic pathways and DNA damage. Yeast, lacking either Cu, ZnSOD or MnSOD, are oxygen intolerant, and the double mutant was hypermutable and defective in sporulation and exhibited requirements for methionine and lysine. A Cu, ZnSOD-null Drosophila exhibited a shortened lifespan.
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PMID:Superoxide radical and superoxide dismutases. 757 5

Preimplantation embryos from a variety of mammalian species contrast markedly in their response to culture in vitro. Murine preimplantation embryos display a wider tolerance than other mammalian species to culture environments, and this has contributed to the development of several effective defined culture media. Embryo coculture on somatic cells remains the most effective method of supporting reasonable rates of bovine preimplantation development in vitro. The patterns of gene expression for several antioxidant enzymes during preimplantation murine and bovine development were examined by use of the reverse transcription-polymerase chain reaction technique to determine whether the differential developmental capacity of mammalian preimplantation embryos in culture may reflect variations in the patterns of expression for a series of antioxidant enzymes. Transcripts for catalase, CuZn-containing superoxide dismutase (CuZn-SOD), Mn-SOD, glutathione peroxidase (GPX), and glutamylcysteine synthetase (GCS) were detected in mouse embryos at all stages of development regardless of in vivo or in vitro development. Preimplantation cow embryos produced by in vitro procedures expressed mRNAs for catalase, CuZn-SOD and GPX, whereas transcripts for Mn-SOD were not detected at any stage. GCS transcripts, although present in stages up to the morula, were not detected in cow blastocysts. Analysis of antioxidant gene expression in both bovine primary oviductal cell monolayer cultures and nonattached, ciliated oviductal cell vesicle cultures revealed a constitutive pattern of expression of all five enzymes for the 8-day culture interval. These experiments suggest that differences in gene expression may contribute to the variation in the ability of embryos to develop in vitro with respect to levels of oxygen and dependence on coculture.
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PMID:Expression of genes encoding antioxidant enzymes in preimplantation mouse and cow embryos and primary bovine oviduct cultures employed for embryo coculture. 757 76

Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.
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PMID:Structure and DNA sequence of the mouse MnSOD gene. 761 35

We investigated the localization of Mn-SOD mRNA in the rat cornea under physiological conditions using in situ hybridization. A Mn-SOD cDNA probe was synthesized by polymerase chain reaction. Slot blot analysis was performed to confirm that the cDNA probe hybridizes with rat Mn-SOD mRNA. Frozen sections of rat cornea were subjected to in situ hybridization using 3H-labeled Mn-SOD cDNA probe. The results demonstrated the expression of Mn-SOD mRNA in the rat corneal epithelial layer. We suggest that corneal epithelial cells are constantly exposed to active oxygen stress even under physiological conditions and synthesize Mn-SOD to protect themselves from the stress.
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PMID:[Localization of Mn-SOD mRNA in rat cornea by in situ hybridization]. 766 Oct 37

Although the mechanisms responsible for chemically induced oxidative stress are under intense investigation, little is known about the effects of prooxidant chemicals on the expression of drug-metabolizing enzymes. We examined the effects of diquat (0.1 mmol/kg, ip) and ciprofibrate (0.025% w/w, diet), chemicals which induce oxidative stress via different biochemical mechanisms, on the steady-state messenger RNA (mRNA) levels of six cytochrome P450 enzymes, seven glutathione S-transferase (GST) isoenzymes, UDP-glucuronosyl transferase 1-06 (UGT1*06), gamma-glutamylcysteine synthetase (gamma GCS), NADP(H):quinone oxidoreductase (quinone reductase), Cu/Zn superoxide dismutase (SOD), catalase, and 18S ribosomal RNA in the livers of male Sprague-Dawley rats. Effects of chemical treatments on mRNA levels were compared to changes in catalytic activities for selected enzymes. Ciprofibrate treatment selectively decreased CYP1A2 mRNA expression, whereas both chemicals suppressed CYP3A2 mRNA expression. CYP4A1 mRNA expression and lauric acid hydroxylase activities were induced by ciprofibrate treatment, whereas diquat treatment moderately increased CYP4A1 mRNA levels without affecting lauric acid hydroxylase activities. The steady-state mRNA levels encoding constitutively expressed GST isozymes (Ya1, Ya2, Yb1, Yb2, and Yc1) were decreased by diquat exposure, and the mRNA encoding four of the five constitutively expressed GSTs (Ya1, Ya2, Yb1, and Yc1) were also decreased by ciprofibrate treatment. Nonconstitutively expressed or low constitutively expressed genes (CYP1A1, CYP2B1, CYP2B2, GST Yc2, GST Yf, and UGT1*06) were not induced by exposure to the prooxidants. Changes in isozyme-specific catalytic activities were more consistent with the observed changes in mRNA expression for the GSTs than for the P450s. Both treatments had inhibitory effects on hepatic GSH biosynthesis by decreasing gamma GCS large-subunit mRNA expression, gamma GCS catalytic activities, and hepatic GSH concentrations. Cu/Zn SOD and quinone reductase mRNA levels were increased after ciprofibrate exposure, whereas Cu/Zn SOD mRNA expression was decreased in the diquat-treated animals. The results of this study indicate that diquat and ciprofibrate can decrease the expression profile of a number of phase I, phase II, and antioxidant enzymes and inhibit GSH biosynthesis. These effects may involve the pretranslational loss of hepatic mRNAs, possibly due to accelerated production of reactive oxygen species.
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PMID:The effects of diquat and ciprofibrate on mRNA expression and catalytic activities of hepatic xenobiotic metabolizing and antioxidant enzymes in rat liver. 767 60

Brain injury in Mongolian gerbil (Merisones unguiculatus) was induced by occluding bilateral common carotid arteries for 60 min followed by reperfusion for 5 or 30 min. Oxygen free radicals in brain tissue were measured by electron spin resonance (ESR) technique, malondialdehyde (MDA) was measured by fluorescence spectrometry, and superoxide dismutase (SOD) was measured by nitrite kit. Oxygen free radicals and MDA were not significantly increased, but activities of T-SOD and Mn-SOD were decreased after 60 min of cerebral ischemia. The free radicals were increased at 5-min reperfusion, and then reduced to the level of ischemia group after 30-min reperfusion. MDA was increased remarkably after reperfusion of 30 min, whereas the activity of SOD continued to decrease. Sodium diethyldithiocarbamate (DTC), i.v. 5-100 mg.kg-1 15 min before occlusion, decreased the production of MDA and increased the activities of T-SOD and Mn-SOD. The formation of oxygen free radicals was depressed by i.v. DTC 50 mg.kg-1. The result suggested that the protective effects of DTC on ischemia-reperfusion-induced brain injury might be induced by scavenging the oxygen free radicals, increasing the Mn-SOD activity and decreasing the production of MDA.
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PMID:[Effects of sodium diethyldithiocarbamate on ischemia-reperfusion-induced brain injury in Mongolian gerbil]. 771 79

Although much evidence favors the concept that dilated cardiomyopathy could be a postviral disease, the actual prevalence and pathogenesis of viral heart disease in dilated cardiomyopathy has not been well explored, since the diagnosis of viral infection is still difficult. The recently developed polymerase chain reaction (PCR) has made it possible to amplify a few copies of viral genome and has shown that viral genomes persist long after viral infection. The PCR is a promising method for testing possible viral etiology. We have found that antiheart antibodies associated with a murine model of myocarditis increased the intracellular free Ca2+ concentration through the activation of Ca(2+)-permeable cation channels in isolated ventricular cells. Marked induction of Mn-SOD and Cu/Zn-SOD mRNA was found in the heart with viral myocarditis and oxygen radicals may play an important role in the pathogenesis of viral myocarditis. Our recent studies revealed an increase in the circulating cytokines in patients with acute myocarditis and cardiomyopathy and suggested that cytokines play some role in the pathogenesis of myocardial injury in these diseases. In our animal model of EMC virus myocarditis, plasma tumor necrosis factor (TNF)-alpha was elevated in the acute stage and exogenously administered anti TNF-alpha antibody improved the survival and myocardial lesion, suggesting the importance of TNF-alpha in the pathogenesis.
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PMID:[Detection of viral genomes in myocarditis]. 773 17

Dihydroxy-acid dehydratase (DHAD) has a [4Fe-4S] cluster and is reported to be facilely inactivated by oxidant stress. To directly assess the biological effects in vivo of superoxide dismutase (SOD) on the oxidant sensitivity of DHAD, we used an Escherichia coli K-12 parent strain (CGSC5073) and derived strains OB 1, OB 2, and OB 3 that lacked one of or both FeSOD and MnSOD. In the K-12 parent strain half the cellular DHAD activity was lost in 15 min at 0.8 atm oxygen, less than 10 microM aerobic nitrofurantoin, or about 5 microM aerobic paraquat (PQ) and in about 1 min at 10 microM aerobic PQ. Oxygen and metabolism were required for PQ to inactivate DHAD in cells; adding dithiothreitol to cell-free extracts did not restore DHAD activity. The Km was not appreciably changed for DHAD that was 50 and 70% inactivated in cells, respectively, by hyperbaric oxygen (HBO) and PQ, compared to cells in exponential, aerobic growth. Thus, active site oxidative impairment of individual enzyme molecules apparently was all-or-none. DHAD activity was greatly decreased when measured in extracts made from strains that lacked both SODs unless SOD was added to cell suspensions before extracts were made. DHAD was more sensitive in strains lacking both SODs than in the parent strain to inactivation by aerobic PQ and HBO. Anaerobic (compared to aerobic) growth increased DHAD specific activity by 20% or less in the parent strain and in strains OB 1 and OB 2 (lacking MnSOD and FeSOD, respectively); however, in strain OB 3 (lacking both SODs) DHAD was increased 60%. DHAD was partially inactivated by the oxidant stress of aerobic growth, but remained in a form detectable by DHAD antibody, and the ratio of active to inactive DHAD decreased greatly in cells lacking SOD. Thus, SOD helped maintain DHAD as an active holoenzyme and benefitted cells growing aerobically or when exposed to low levels of PQ.
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PMID:Dihydroxy-acid dehydratase, a [4Fe-4S] cluster-containing enzyme in Escherichia coli: effects of intracellular superoxide dismutase on its inactivation by oxidant stress. 777 72


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