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)

Recent evidence has suggested that ischemia-reperfusion injury is fundamental to the pathogenesis of acute pancreatitis. This study was designed to determine whether acute pancreatitis is associated with elevated serum manganese superoxide dismutase (MnSOD), a key antioxidant enzyme, considered a marker of ischemia-reperfusion injury in myocardial infarction. Thirty-four patients with acute pancreatitis had measurements of MnSOD on days 0, 2, and 5 after recruitment. The patients were recruited within 12 h of admission to hospital and had measurements of MnSOD on days 0, 2, and 5. Patients with severe acute pancreatitis had significantly elevated serum MnSOD concentrations on days 2 and 5 compared with patients with mild acute pancreatitis, but not on the day of recruitment. Elevated serum MnSOD correlated with peripheral plasma markers of lipid peroxidation (malondialdehyde) and neutrophil activation (myeloperoxidase) and was associated with decreased plasma ascorbic acid concentrations. The serial measurement of serum MnSOD may prove useful as a marker of the effectiveness of treatment designed to limit ischemia-reperfusion injury in patients with severe acute pancreatitis.
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PMID:Manganese superoxide dismutase: a marker of ischemia-reperfusion injury in acute pancreatitis? 921 96

Understanding the fundamental mechanism of apoptosis is crucial to developing therapeutic strategies for controlling apoptosis in diseased tissues. We are using model systems with relevance to cancer treatment to investigate the mechanism of apoptosis. Subtraction hybridization cloning was used to identify transcripts present at higher levels in regressing vs. normal prostate; these may be important for apoptosis. One of the genes cloned from regressing prostate is also upregulated in the murine W7.2 lymphocyte cell line induced to undergo apoptosis by treatment with the synthetic glucocorticoid, dexamethasone. This gene encodes a mu class glutathione S-transferase (EC 2.5.1.18), a protein that can protect the cell against oxidative stress by repairing oxidized lipids, proteins, and DNA. Glutathione S-transferase expression does not increase with dexamethasone treatment of lymphocyte cell lines expressing nonfunctional glucocorticoid receptors or a mutation in the apoptotic pathway. Other antioxidant defenses, including catalase (EC 1.11.1.6) and superoxide dismutase (EC 1.15.1.1), decline following dexamethasone treatment of W7.2 cells. Overexpression of the bcl-2 oncogene protects these cells against dexamethasone-mediated apoptosis and prevents the decrease in antioxidant enzyme activity. These findings support the hypothesis that control of the cellular redox state is important to the mechanism of glucocorticoid-mediated lymphocyte apoptosis. Another model system we are using is tumor necrosis factor-alpha treatment of MCF-7 human breast cancer cells. Our preliminary results suggest that, in this system, activation of nuclear factor-kappa B and increased expression of manganese superoxide dismutase may afford protection from apoptosis.
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PMID:Modulation of antioxidant defenses during apoptosis. 940 33

Sera of 146 patients with acute EBV, HAV, HBV, CMV, HSV, and rubella virus infections, and sera from 35 healthy controls were tested for the antioxidant enzyme manganese superoxide dismutase (MnSOD). An enzyme immunoassay that detects all isomeres of the enzyme was developed. The mean MnSOD value of healthy controls was 107 ng/ml. In HAV, HBV and EBV infections characterized by viral replication in internal organs, there was an average 5-fold rise of serum MnSOD, whereas in viral infections with low direct cytopathogenity, such as rubella, CMV and HSV, the MnSOD levels showed only minor rises. These sera were also tested for autoantibodies against MnSOD using a novel sensitive indirect enzyme immunoassay. The average IgM anti-MnSOD concentration in sera of healthy controls was 112 GU. In sera of patients with acute HBV, CMV, HSV or rubella virus infections IgM anti-MnSOD values were only slightly raised above the cut-off level. In contrast, in some patients with acute EBV infections anti-MnSOD concentrations rose up to 20-fold of normal values. In HAV infections the same phenomenon was observed in patients who had reactivated EBV infections. These findings indicate that EBV may facilitate the B-cell response to MnSOD. These autoantibodies may inhibit the protective function of MnSOD and prolong the disease by oxygen injury. Our concept on the pathogenic effect of the autoantibodies against MnSOD emphasizes the importance of the antioxidant enzyme in viral infections.
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PMID:Manganese superoxide dismutase (MnSOD) and autoantibodies against MnSOD in acute viral infections. 959 38

Repetitive courses of maternal prenatal glucocorticoids are often used in high-risk pregnancies with threatening preterm labor to induce lung maturation, but the effects on the cellular oxidant-antioxidant balance in the fetal lung have not been evaluated. We investigated the effect of repetitive treatment with glucocorticoids, beginning early in gestation, on oxidative stress in the preterm ovine lung. Pregnant ewes were randomized to receive one, two, three, or four doses of 0.5 mg/kg betamethasone or saline placebo at 7-day intervals on 104, 111, 118, and 124 days gestation (n = 11 for each group). All lambs were delivered preterm at 125 days gestation, and lung tissue was assayed for antioxidant enzymes, lipid hydroperoxides, and carbonyl proteins. Lung manganese superoxide dismutase, catalase, and glutathione peroxidase activity increased after 1 dose of betamethasone given at 104 days gestation, whereas copper-zinc superoxide dismutase activity increased after 2 doses given at 104 and 111 days gestation. The activity of all four antioxidant enzymes further increased with additional doses and was maximal after four doses of betamethasone. Lung lipid hydroperoxide levels and carbonyl protein content decreased stepwise after each dose of betamethasone and were lowest after four doses. Repetitive prenatal glucocorticoid therapy increases antioxidant enzyme activity and reduces oxidative stress in the lungs of preterm lambs, and these effects begin early in gestation and persist for 2-3 wk.
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PMID:Repetitive prenatal glucocorticoid therapy reduces oxidative stress in the lungs of preterm lambs. 965 86

Apoptosis has been documented as a fundamental component of the life cycle of many cell types. One of the characteristics of this process is the cleavage of genomic DNA into oligonucleosomal fragments. The multifunctional cytokine TGF-beta 1 has been described to induce apoptosis in cultured hepatocytes although in this condition DNA fragmentation has not been detected. We investigated whether TGF-beta 1-induced apoptosis was associated with DNA fragmentation and was affected by PMA. Agarose gel electrophoresis of TGF-beta 1-treated hepatocytes shows a typical ladder-like pattern of DNA fragments and PMA, a selective stimulator of protein kinase C, diminishes the DNA fragmentation and cell death. It has been described that the antioxidant enzyme systems play an important role in the control of apoptosis and that the apoptogenic ability of TGF-beta 1 is through the inhibition of antioxidant enzyme expression in cultured hepatocytes [8]. However, PMA does not induce significant changes levels of manganese superoxide dismutase, copper-zinc superoxide dismutase and catalase mRNAs. Our data reveal that the attenuation of TGF-beta 1-induced DNA fragmentation by PMA is not associated with changes in the expression of antioxidant systems and is probably due selectively to the stimulation of protein kinases C.
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PMID:Effect of phorbol ester (PMA) on antioxidant enzyme expression in TGF-beta 1-induced apoptosis in primary cultures of hepatocytes. 969 11

NIH/3T3 mouse embryo fibroblasts were transfected with the cDNA for manganese superoxide dismutase (MnSOD). Previous studies showed characteristic unique AE profiles in nonsynchronous populations of parental, control plasmid-transfected, and MnSOD-overexpressing NIH/3T3 cell lines. However, the present study showed that during S and M phases of the cell cycle, antioxidant enzyme (AE) levels were altered in MnSOD-overexpressing cell lines towards levels in S and M phases of parental and control plasmid-transfected cells. Because of the demonstration that MnSOD overexpression inhibits cell growth in both nonmalignant and malignant cells, the present study was designed to measure AEs, reactive oxygen species (ROS), and glutathione levels in various phases of the cell cycle in both parental NIH/3T3 cells and NIH/3T3 cells overexpressing MnSOD, to try to determine whether AEs, ROS, and glutathione levels could have a possible regulatory role in cell cycle progression. In all cell lines studied, ROS levels were lower in M than S phase of the cell cycle. Total glutathione and glutathione disulfide levels were greatly increased during the M phase of the cell cycle compared with quiescence and S phase in all cell lines studied. This suggests that oxidative stress exists in M phase of the cell cycle with total glutathione levels increased to decrease oxidative stress. Analysis of MnSOD-overexpressing cell clones showed a correlation of decreased cell growth with an increase in ROS in S phase of the cell cycle and a decrease in glutathione in mitosis. The data strongly suggest that specific levels of cell redox state are necessary for cells to successfully progress through the various phases of the cell cycle.
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PMID:Modulation of antioxidant enzymes, reactive oxygen species, and glutathione levels in manganese superoxide dismutase-overexpressing NIH/3T3 fibroblasts during the cell cycle. 973 55

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known to decrease manganese superoxide dismutase (MnSOD) activity in colonic mucosa. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is absent or decreased in most tumours, including those from the colon. This study was designed to determine the effects of high dietary lipid and iron levels on MnSOD activity during the early weeks of colon carcinogenesis. Male Fischer-344 rats were fed 20% lipid diets of either corn oil or menhaden oil containing adequate iron (35 mg/kg) or supplemental iron (535 mg/kg). Rats from each diet were divided into carcinogen treatment groups and given two weekly injections of either azoxymethane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collected 1, 6 and 12 wk following injections and analysed for MnSOD activity, mineral concentration and nuclear aberrations. Results showed that iron supplementation increased nuclear aberrations, and decreased manganese concentration and MnSOD activity in colonic mucosa ot control animals. AOM, and interaction of iron and AOM, also decreased MnSOD activity. A decrease in the activity of this enzyme during carcinogenesis may be one mechanism whereby these dietary factors ultimately increase tumour risk.
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PMID:Decrease of manganese superoxide dismutase activity in rats fed high levels of iron during colon carcinogenesis. 973 29

The lipid biomediator lysophosphatidic acid (LPA) elicits a unique response in hippocampal neurons, LPA induces neuronal apoptosis. This study explores the effects of LPA on cells with neuronal properties, nerve growth factor-differentiated PC6 cells, a clone of PC12 cells. LPA induced apoptosis in these cells as assessed by chromatin condensation, terminal dUTP nick end-labeling of DNA, protection against these nuclear alterations by a general caspase inhibitor and the lack of release of lactic dehydrogenase. LPA caused oxidative stress, namely a decreased reduction of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. This oxidative stress appears to be of functional significance, since cells were protected by pretreatment with the antioxidant propyl gallate and by stable transfection with cDNA encoding the antioxidant enzyme, manganese superoxide dismutase. Mitochondrial and nitric oxide participation in LPA-induced apoptosis are suggested by the protection afforded by pretreatment with either cyclosporin A, an inhibitor of mitochondrial permeability transition, or nitric oxide synthase inhibitors. The nitric oxide synthase inhibitor findings are novel, since to our knowledge, LPA has not heretofore been associated with an increase in nitric oxide. In addition, as observed for many neurotoxic agents, insulin-like growth factor I protected against LPA-induced apoptosis of PC6 cells.
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PMID:Lysophosphatidic acid and apoptosis of nerve growth factor-differentiated PC12 cells. 975 97

There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.
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PMID:Manganese superoxide dismutase overexpression attenuates MPTP toxicity. 984 95

Our previous studies noted the oxidative stress of unilateral ureteral obstruction (UUO). Now, we seek to explore whether UUO affects the intrinsic cellular antioxidants and triggers heat shock protein (HSP-70) and whether these are still highly expressed after reversal of the UUO (R-UUO). In addition, we designed the experiment to determine whether this expression of HSP-70 is a localized or a generalized response. Male Sprague-Dawley rats (125-150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedures at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstructed) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was observed: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham in R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham values. It is possibly the result of a systemic effect from the free radicals produced by the oxidative stress of the UUO. The antioxidant enzyme, manganese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP-70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, during R-UUO, was not different from sham (P, ns). The contralateral (intact) right kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. We conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cellular antioxidant enzyme, manganese superoxide dismutase, showed a significant and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO or in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO.
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PMID:Increased heat shock protein-70 in unilateral ureteral obstruction in rats. 988 18


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