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)

In many pathological situations, tissue damage is caused by cellular generation of superoxide free radicals (O2-). These active species are generated during post-ischemic reperfusion of organs, in hyperoxic tissue, during acute and chronic inflammation and during exposure to ionizing radiation. Exogenous superoxide dismutase (SOD) was shown to significantly prevent such damage. The genes for human cytosolic Cu/ZnSOD and mitochondrial MnSOD were cloned and introduced into an E. coli expression system. The proteins were expressed in high yields and purified to homogeneity, yielding pharmaceutical-grade materials. These enzymes were used in a variety of in vivo animal models for the demonstration of their protective effects against oxidative damage. Comparative pharmacokinetic studies in rats have revealed that the half-life of Cu/ZnSOD was 6-10 min., while that of MnSOD was 5-6 hours, thus indicating that MnSOD may be superior to Cu/ZnSOD for the treatment of chronic diseases. Indeed, MnSOD was found to be effective as an anti-inflammatory agent in the rat carrageenan induced paw edema acute inflammation model. Both enzymes were also effective in ameliorating post-irradiation damage in mice exposed to whole-body or localized chest X-ray radiation.
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PMID:Recombinant human superoxide dismutases: production and potential therapeutical uses. 207 Oct 44

Escherichia coli growing anaerobically respond to NO3- with a approximately 3-fold induction of active FeSOD and a approximately 5.5-fold induction of an inactive, but activatable form of MnSOD (pro-MnSOD). Paraquat, which mediates anaerobic electron flow to NO3-, increased the induction of pro-MnSOD to approximately 2.5-fold. Strains with defects in the SOD genes or which lacked nitrate reductase activity failed to accumulate active or pro-forms of SODs in response to NO3- +/- PQ++. Diamide caused anaerobic induction of active MnSOD and this effect was also observed in a glutathione-negative strain. These inductions required de novo synthesis of protein, even when cell content of pro-MnSOD had been elevated by exposure to NO3- +/- PQ++ prior to addition of diamide. These results indicate that oxidation of a cell component increases biosynthesis of the SOD gene product and this postulated oxidation can be caused by terminal electron acceptors, such as dioxygen or NO3-. In addition, it appears that insertion of the correct metal can be rate-limiting, leading to competition by other metals and to the accumulation of inactive, incorrectly substituted pro-forms. Metal insertion may be dependent upon the valence of the metal, which may be influenced, in turn, by the redox status of the cells. Diamide and redox active agents such as ferricyanide may thus allow anaerobic production of active MnSOD by favoring the production of a complexed form of Mn(III) which can compete favorably with other metal cations for the active site of nascent MnSOD.
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PMID:Anaerobic inductions of active forms of superoxide dismutases in Escherichia coli. 207 Oct 46

A 1.8 kb PstI fragment from Halobacterium halobium DNA was found to hybridize to synthetic oligonucleotide probes constructed by using the sequence of the N-terminus of a Mn-containing superoxide dismutase purified from H. halobium. The entire insert containing a 600-bp coding sequence for Mn-SOD and its 5' and 3' flanking regions was sequenced. The derived amino acid sequence of the structural gene showed a similarity to other manganic and iron-containing superoxide dismutases in normally conserved regions. Primer extension analysis of the H. halobium Mn-SOD mRNA showed that gene transcription begins 14 bases upstream of the translational start. A Shine-Dalgarno sequence and archaebacterial consensus promoter sequences were observed. Several other promoter and terminator nucleotide sequences homologous to prokaryotic and eukaryotic organisms were found.
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PMID:Halobacterium halobium Mn-SOD gene: archaebacterial and eubacterial features. 207 Oct 48

The 2.9 A resolution structure of iron superoxide dismutase (FeSOD) (EC 1.15.1.1) from Pseudomonas ovalis complexed with the inhibitor azide was solved. Comparison of this structure with free enzyme shows that the inhibitor is bound at the open coordination position of the iron, with a bond length of 2.0 A. The metal moves by 0.4 A into the trigonal plane to produce an orthogonal geometry at the iron. Binding of the inhibitor also causes a movement of the axial ligand (histidine 26) away from the metal, a lengthening of the iron-histidine bond, and a rotation of the histidine 74 ring. The inhibitor possesses contacts in the binding pocket with a pair of conserved tryptophan residues and with the side chains of tyrosine 34 and glutamine 70. This glutamine is conserved between all FeSODs, but is absent in MnSOD. Comparisons with MnSOD show that a different glutamine which possesses the same interactions in the active site as Gln70 in FeSOD is conserved at position 154 in the overall SOD sequence, implying that while manganese and FeSODs are structural homologues in a global sense, their functional and evolutionary relationship is that of second-site mutation revertants.
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PMID:The structure of iron superoxide dismutase from Pseudomonas ovalis complexed with the inhibitor azide. 207 85

The combined effect of Vit. A and E, selenium, cysteine and BHA on 3MC-induced lung cancer in Wistar rats was investigated. The supplementation of these compounds at their safe doses reduced the incidence of lung cancer from 47.2% to 31.6% (P less than 0.05). The total superoxide dismutase (SOD) and Mn-SOD activities in the lung cancer tissue were much lower than those in the normal tissue (P less than 0.001). It is possible that in the early stage of carcinogenesis, this change occurs only in the limited focus and does not affect the enzyme level as a whole, so SOD assay of peripheral blood can not reflect the carcinogenesis status in the lung.
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PMID:[Inhibitory effect of micronutrients and BHA on lung cancer induced in rats]. 207 36

Extracellular superoxide dismutase (EC-SOD) is the major SOD isoenzyme in extracellular fluids, but occurs also in tissues. The sites and characteristics of the synthesis of the enzyme are unknown. The occurrence of EC-SOD in cultures of a large panel of human cell lines was assayed by means of an e.l.i.s.a. Unlike the situation for the intracellular isoenzymes CuZn-SOD and Mn-SOD, expression of EC-SOD occurs in only a few cell types. None of the ten investigated suspension-growing cell lines produced EC-SOD. Among normal diploid anchorage-dependent cell lines, expression was found in all 25 investigated fibroblast cell lines, in the two glia-cell lines, but not in six endothelial-cell lines, two epithelial-cell lines or in two amnion-derived lines. Among neoplastic anchorage-dependent cell lines expression was found in 13 out of 29. EC-SOD was secreted into the culture medium by cell lines expressing the enzyme. The rate of EC-SOD synthesis varied by nearly 100-fold among the fibroblast lines and remained essentially constant in the individual lines during long-term culture. In the nine investigated cases, the secreted EC-SOD was of the high-heparin-affinity C type. It is suggested that tissue EC-SOD is secreted by a few well-dispersed cell types, such as fibroblasts and glia cells, to diffuse subsequently around and reversibly bind to heparan sulphate proteoglycan ligands in the glycocalyx of the surface of most tissue cell types and in the interstitial matrix.
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PMID:Expression of extracellular superoxide dismutase by human cell lines. 210 74

A gene encoding superoxide dismutase (SOD) was cloned from the archaebacterium Methanobacterium thermoautotrophicum, the first example from an anaerobic bacterium. The deduced amino acid sequence showed overall similarity to sequences of known Mn- and Fe-SODs from aerobic organisms. Judging from a detailed sequence comparison, the cloned SOD gene is classified as Mn-SOD. By comparison of Mn-SOD sequences among various species it was suggested that archaebacterial superoxide dismutase is a direct descendant of a primordial enzyme. Between a putative promoter and the start codon there is an inverted repeat sequence which is also found in the counterpart of Halobacterium halobium.
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PMID:Characterization of a superoxide dismutase gene from the archaebacterium Methanobacterium thermoautotrophicum. 212 8

The Mn superoxide dismutase gene of Escherichia coli was subcloned into the E. coli-Anacystis nidulans shuttle vector pSG111 to make the plasmid pMYG1. Transformation of E. coli HB101 with pMYG1 resulted in a 6-fold increase in superoxide dismutase activity. There was also induction of Mn superoxide dismutase in the transformants upon exposure to paraquat, as evidenced by dramatically increased levels of the Mn superoxide dismutase polypeptide in cytoplasmic extracts and a 16-fold further increase in superoxide dismutase activity. As well, the E. coli transformants showed resistance to paraquat-mediated inhibition of growth. Anacystis nidulans, a cyanobacterium that has no detectable Mn superoxide dismutase and is, consequently, very sensitive to oxidative stress, was also transformed with pMYG1. The transformants had detectable levels of Mn superoxide dismutase protein and showed resistance to paraquat-mediated inhibition of growth and photobleaching of pigments. Paraquat is known to promote formation of the superoxide radical anion, O2-., and thus the data have been interpreted as indicating that the cloned Mn superoxide dismutase provides protection in both E. coli and A. nidulans against damage attributable to O2-..
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PMID:Cloned manganese superoxide dismutase reduces oxidative stress in Escherichia coli and Anacystis nidulans. 215 7

Superoxide dismutase (SOD) activity in hepatocellular carcinoma (HCC) tissue was studied. It was observed that activities of total SOD, Cu, Zn-SOD and Mn-SOD in HCC tissue were lower than those in normal liver tissues respectively (P less than 0.001 & 0.01 less than P less than 0.05). SOD activity in poorly differentiated HCC tissue was lower than that in well differentiated HCC tissue. Contents of copper, zinc and manganese in HCC tissues were lower than those in normal liver tissues respectively (P less than 0.001 & P less than 0.01). This study suggests that decreased content of copper, zinc and manganese may be one of the factors that lead to impairment of SOD activity. The characteristic of lower SOD activity in HCC tissue and poorly differentiated HCC tissue may be a negative regulation to limitless proliferation and poor differentiation of liver cancer cells.
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PMID:[Superoxide dismutase activity in tissues from 19 cases of hepatocellular carcinoma]. 216 38

Cu,Zn superoxide dismutase (Cu,Zn-SOD; EC 1.15.1.1) is known to be inhibited slowly by H2O2. Using EPR and the spin traps 5,5-dimethyl-1-pyrroline 1-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN), we have shown that Cu,Zn-SOD catalyzes the formation of "free" .OH radicals from H2O2 in pH 7.6 bicarbonate buffer. Supporting evidence includes the following: (i) H2O2 and active Cu,Zn-SOD are required to yield significant signals from spin-trap-OH adducts. (ii) With O2-., Cu,Zn-SOD causes the appearance of intense resonance signals due to DMPO-OH adducts. These signals were inhibited strongly by catalase. (iii) With H2O2, Cu,Zn-SOD, and DMPO, radical scavengers formate and azide, but not ethanol, decrease DMPO-OH signals while causing new intense signals due to their corresponding DMPO-radical adducts. Failure of ethanol to quench DMPO-OH signals is discussed in light of the positively charged active channel of the enzyme. (iv) With PBN as a spin trap, ethanol quenches .OH radical signals and yields PBN-trapped hydroxyethyl radical signals. (v) Mn-SOD does not catalyze "free" .OH radical formation and it also exerts no effect on the signals of DMPO-OH adducts when added together with the Cu,Zn-SOD. The capacity of Cu,Zn-SOD to generate "free" .OH radicals from H2O2 may in part explain the biological damage associated with elevated intracellular SOD activity.
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PMID:Copper, zinc superoxide dismutase catalyzes hydroxyl radical production from hydrogen peroxide. 216 16


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