Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.01 seconds)

The effect of oxygen toxicity on the development of mammalian embryos was assessed by the use of superoxide dismutase (SOD), a potent scavenger of superoxide radicals. Mouse pronuclear embryos recovered 17 h after human chorionic gonadotropin (hCG) were cultured in medium BWW at 37 degrees C under an atmosphere of 5% CO2 in air. Culture of mouse pronuclear embryos in the presence of Cu.Zn-SOD (500 micrograms/ml) significantly increased the blastulation rate (44.6%) when compared with the control culture system (4.2%). Essentially the same effects were observed in SOD containing either Mn or Fe in the catalytic center. Heat treatment of the SOD preparation, and the addition of anti-SOD antibodies to the culture medium, significantly reduced the attenuation of the two-cell block by SOD, indicating that this effect is SOD dependent. SOD activity was detected in rabbit oviduct fluid (3.675 +/- 3.084 mIU/mg protein) by electron spin resonance. These results suggest that active oxygen is involved in the two-cell block phenomenon in mouse embryos exposed to air and that SOD in the oviduct may play an important role in the protection of embryos from superoxide radicals.
Mol Reprod Dev 1991 Apr
PMID:Involvement of superoxide radicals in the mouse two-cell block. 164 68

The aim of this work was to study the ability of human alveolar macrophages (AM) of 10 healthy smokers to inactivate alpha 1-proteinase inhibitor (alpha 1PI). Purified alpha 1PI was incubated for 45 min, with human alveolar macrophages before and after stimulation by phorbol myristate acetate (PMA) or opsonized zymosan. As a positive control, the same experiments were performed in parallel with blood human neutrophils (PMN). Results are expressed as percentage of inactivation of alpha 1PI as evaluated from its inhibitory activity against porcine pancreatic elastase. A strong correlation (r = 0.99) was shown when inhibitory activity of alpha 1PI was evaluated against porcine pancreatic elastase or human neutrophil elastase. Unstimulated AM (1.57 +/- 0.9%) as well as stimulated AM (PMA: 1 +/- 0.4%; zymosan: 3 +/- 0.6%) were unable to inactivate alpha 1PI. Gel electrophoresis of alpha 1PI demonstrated that AM before or after stimulation induced a slight proteolysis of alpha 1PI, whereas both cleaved and complexed alpha 1PI were found when alpha 1PI was incubated with activated PMN. Both unstimulated (22 +/- 2.6%) and activated PMN (PMA: 91.7 +/- 4.7%; zymosan: 90 +/- 5.5%) were responsible for a significant inactivation of alpha 1PI. Catalase, in contrast to superoxide dismutase, was responsible for a near complete protection of alpha 1PI inactivation by PMN. To better determine the role of PMN secretory products, especially myeloperoxidase (MPO), we also investigated the effect of zymosan-activated PMN supernatants or of purified MPO on the alpha 1PI-AM reaction. MPO assay in PMN supernatants demonstrated that activated neutrophils released significant amounts of MPO (16.8 +/- 4.1 U/ml), whereas MPO was undetectable in activated AM supernatants.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1991 Nov
PMID:Oxidative inactivation of alpha 1-proteinase inhibitor by alveolar macrophages from healthy smokers requires the presence of myeloperoxidase. 165 63

Unsporulated oocysts of Eimeria tenella have high superoxide dismutase (SOD: superoxide:superoxide oxidoreductase, EC 1.15.1.1.) activity and contain several electrophoretically distinct forms of the enzyme, including two forms of Cu/Zn-containing SOD, two forms of Fe-SOD and two forms of Mn-SOD. SOD activity remains high during 12 h of sporulation but diminishes slowly during prolonged sporulation. Oocysts sporulated for 48 h have low levels of superoxide dismutase and contain only one form of the enzyme (Mn-SOD), which was also found in sporozoites. In vitro, sporozoites are oxidant-sensitive and die within minutes of superoxide radical (O2-) generation but SOD/catalase and mannitol protect sporozoites against oxidative damage. These data suggest that E. tenella sporulated oocysts and sporozoites lack soluble cytoplasmic SOD and that this deficiency may contribute to the oxidant sensitivity of the parasite.
Mol Biochem Parasitol 1991 Aug
PMID:Superoxide dismutases in Eimeria tenella. 165 47

Exposure of diploid fetal human fibroblasts (IMR-90) to superoxide generated by dihydroxyfumarate resulted in increased collagen synthesis. The synthesis of type III collagen was stimulated to a greater extent than the synthesis of type I collagen. The stimulation of collagen synthesis was abolished by superoxide dismutase. Our observations suggest that superoxide may play a role in the regulation of collagen synthesis and may modulate differential collagen gene expression. These observations may explain the increased synthesis of collagen in tissues following inflammation or exposure to oxidant conditions.
Cell Mol Biol 1991
PMID:Stimulation of collagen synthesis in fibroblast cultures by superoxide. 166 36

Two forms of superoxide dismutase, CuZn-SOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic rats using both radio-immunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because of the proliferation of renal tubular epithelium. However, the total CuZnSOD content of the kidneys did not increase and, because of the epithelial proliferation, the CuZnSOD concentration in each proximal tubular cell was decreased. Armanni-Ebstein lesions were found in the distal tubules 8 and 12 weeks after the induction of diabetes. The cells in these lesions were intensely stained for CuZnSOD, suggesting an adaptive response to the enhanced oxidative stress. The MnSOD staining in the thick ascending limbs of Henle's loops was enhanced in the diabetic kidneys, while that in the cortical tubules was unaltered. MnSOD was assumed to increase in response to hypermetabolism associated with the proliferation of renal tubules. This was most marked in the cells which were rich in mitochondria, again suggesting an adaptive response to enhanced oxidative stress induced by diabetes mellitus. The glomeruli of both the diabetic and control groups were not stained for SODs, and no significant microscopic change was found even 12 weeks after the induction of diabetes mellitus.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Effect of diabetes mellitus induced by streptozotocin on renal superoxide dismutases in the rat. A radioimmunoassay and immunohistochemical study. 167 79

The effects of propranolol (PRO) and atenolol (ATE) on adult canine myocytes exposed to 30 min anoxia (A:95% N2/5% CO2) and subsequent reoxygenation (R:95% O2/5% CO2) for up to 20 min was investigated. In some studies, comparison of effects were made with that of superoxide dismutase (SOD). Although anoxia alone produced only minimal injury, reoxygenation in the absence of the beta-blockers or SOD was associated with significant losses of cellular viability, elevated release of cellular lactate dehydrogenase, and increased formation of lipid peroxidation products. Myocytes exposed to A/R in the presence of d,1-PRO (20, 200 microM) were afforded substantial, concentration-dependent protection during 20 min reoxygenation. Significant protection was also observed in the presence of 2 microM d-PRO (non-active beta-blocker), but only after a longer preincubation period (2 h). SOD (10 micrograms/ml) provided equi-potent protection to that of 200 microM d,1-PRO. By contrast, the more water-soluble beta-blocker, ATE (200 microM), offered only minor protection. Electron Spin Resonance spin trapping studies using alpha-phenyl-tert-butylnitrone (PBN) were also performed with A/R myocytes in the presence or absence of drug treatment. Short-term (10 min) exposure to d,1-PRO (200 microM) prior to A/R, or to SOD, resulted in a 71-84% reduction in total PBN lipid radical adduct formation (alkoxyl; alpha H = 2.0-2.5 G, alpha N = 13.5-13.75 G); long-term exposure (2 h) to 2 microM d-PRO resulted in a 51% reduction. These data suggest that the superoxide anion was an initiator of events leading to subsequent lipid radical formation and that the anti-peroxidative properties of PRO appear to be independent of beta-receptor blockade.
J Mol Cell Cardiol 1991 Nov
PMID:Propranolol reduces anoxia/reoxygenation-mediated injury of adult myocytes through an anti-radical mechanism. 168 65

Equipotential lines were calculated, using the Poisson-Boltzmann equation, for six Cu,Zn superoxide dismutases with different protein electric charge and various degrees of sequence homology, namely those from ox, pig, sheep, yeast, and the isoenzymes A and B from the amphibian Xenopus laevis. The three-dimensional structures of the porcine and ovine superoxide dismutases were obtained by molecular modelling reconstruction using the structure of the highly homologous bovine enzyme as a template. The three-dimensional structure of the evolutionary distant yeast Cu,Zn superoxide dismutase was recently resolved by us, while computer-modelled structures are available for X. laevis isoenzymes. The six proteins display large differences in the net protein charge and distribution of electrically charged surface residues but the trend of the equipotential lines in the proximity of the active sites was found to be constant in all cases. These results are in line with the very similar catlytic rate constants experimentally measured for the corresponding enzyme activities. This analysis shows that electrostatic guidance for the enzyme-substrate interaction in Cu,Zn superoxide dismutases is related to a spatial distribution of charges, arranged so as to maintain, in the area surrounding the active sites, an identical electrostatic potential distribution, which is conserved in the evolution of this protein family.
J Mol Biol 1992 Jan 05
PMID:Evolutionary conservativeness of electric field in the Cu,Zn superoxide dismutase active site. Evidence for co-ordinated mutation of charged amino acid residues. 173 Oct 78

Mutants of Escherichia coli that are devoid of superoxide dismutase (SOD) fail to grow in aerobic minimal medium. This is largely because of the O2- sensitivities of several amino acid biosynthetic pathways, since amino acid supplements can restore growth, albeit at a slow rate. We now report that growth in amino acid-supplemented medium can be further stimulated by the presence of extracellular osmolytes. Osmolytes also partially suppress the amino acid requirements of the SOD mutant. These data suggest that the combination of oxidative injury and turgor pressure permeabilizes the cell envelope and that critical metabolites, including the limiting products of damaged biosynthetic pathways, escape from the cell. External osmolytes may offer protection by countervailing the usual turgor pressure and thus stabilizing the damaged envelope. This model is consistent with the previous observation that deficiency of cell wall components is lethal to SOD mutants. A pseudorevertant that can grow at a moderate rate in normosmotic medium without amino acid supplementation has been obtained (J. A. Imlay and I. Fridovich, Mol. Gen. Genet. 228:410-416, 1991). Analysis suggests that the suppressor mutation allows the envelope either to resist or to tolerate oxidative lesions. Study of the pseudorevertant may illuminate the molecular basis of this oxidative envelope injury.
 ...
PMID:Suppression of oxidative envelope damage by pseudoreversion of a superoxide dismutase-deficient mutant of Escherichia coli. 173 28

A gene encoding superoxide dismutase (EC 1.15.1.1., SOD) was isolated from a plasmid library of chromosomal DNA from Listeria ivanovii by functional complementation of an SOD-negative Escherichia coli host. The nucleotide sequence of the cloned gene was determined and contained an open reading frame which codes for a protein of 202 amino acid residues (calculated molecular weight 22755 Da including the amino-terminal methionine residue). Comparison of the deduced amino acid sequence of L. ivanovii SOD with previously reported SOD amino acid sequences revealed considerable homologies with Fe- and Mn-dependent SODs. Enzymatic analyses using cell lysates and the purified recombinant enzyme indicated that this SOD is manganese-dependent. The recombinant SOD accounted for up to 30% of the total soluble protein in recombinant E. coli and protected sodA sodB mutants against the toxic effects of paraquat. Subunits of the recombinant Listeria SOD and of both E. coli SODs formed enzymatically active hybrids in vivo.
Mol Gen Genet 1992 Jan
PMID:Cloning of a superoxide dismutase gene from Listeria ivanovii by functional complementation in Escherichia coli and characterization of the gene product. 173

To clarify whether ischemic liver injury is due to ischemia itself or reperfusion, histopathological and functional changes in the liver were examined before and after liver ischemia in rats with porto-systemic collateral channels. Effects of oxygen-derived free radical scavengers or an inhibitor of platelet aggregation on development of ischemic liver injury were also examined. Liver ischemia was produced by ligation of the portal vein and hepatic artery at liver hilum for 1 hr. The primary lesion of ischemic liver injury was cloudy swelling of liver cells in the periportal and midzonal regions; it developed during ischemia. The cloudy swelling of liver cells induced uneven distribution of sinusoidal blood flow after reperfusion, and consequently individual liver cell necrosis and focal hepatocellular necrosis in the midzonal regions developed later. Elevation of cytoplasmic enzyme activities in the serum after reperfusion was due to leakage across the damaged plasma membrane of liver cells. The treatment with superoxide dismutase, catalase, or heparin had not altered the liver injury that was attributed to ischemia, biochemically and histologically. These results suggest that ischemic liver injury is due to liver cell damage developed during ischemia, and that the ischemic liver injury is not alleviated or prevented by superoxide dismutase, catalase, or heparin.
Exp Mol Pathol 1991 Dec
PMID:Mechanism of liver injury following ischemia. 174 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>