Disease relevance of SOD1

• Superoxide dismutase (SOD) has been documented to limit myocardial infarct size in the richly collateralized dog heart [1].
• Autosomal dominant amyotrophic lateral sclerosis: a novel mutation in the Cu/Zn superoxide dismutase-1 gene [2].
• These data suggest that intracellular delivery of superoxide dismutase prevents oxygen-induced cell damage and that superoxide is an important mediator of cellular oxygen toxicity [3].
• We conclude that intravenous polyethylene glycol-conjugated superoxide dismutase does not increase superoxide dismutase activity in the brain despite global ischemia and reperfusion [4].
• Hypoxia or superoxide dismutase/catalase pretreatment also abolished the post-ANA or leukotriene C4 O(Ca++)E-augmented myorelaxation [5].

High impact information on SOD1

• The effects of xanthine plus xanthine oxidase were inhibited by catalase but not by superoxide dismutase, suggesting that H2O2 was responsible [6].
• The production of endothelin upon stimulation with thrombin (4 U/ml) was potentiated by L-NG-monomethyl arginine and methylene blue and reduced by superoxide dismutase and 8-bromo cyclic guanosine 5'-monophosphate (GMP), while the basal release of the peptide was unaffected [7].
• The possible role of intravascular O2- as a mediator of heat shock response was evaluated by its specific inhibition by the intravenous infusion of recombinant human superoxide dismutase (SOD) [8].
• The addition of either deferoxamine or superoxide dismutase to the cardioplegic solution significantly (but not completely) preserved vasomotor responses of coronary microvessels to serotonin (9 +/- 6% and 11 +/- 4%, respectively; P < .05) or bradykinin (72 +/- 4% and 87 +/- 3%, respectively; P < .05) [9].
• The NO scavenger oxyhemoglobin and methylene blue increased coronary resistance and decreased cGMP release (basal release, 342 +/- 4 fmol/min), whereas superoxide dismutase reduced coronary resistance [10].

Chemical compound and disease context of SOD1

• Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg) [11].
• We also conclude that allopurinol, but not superoxide dismutase/catalase, possibly due to the administration regimens used in this series, is able to attenuate the trypsin activation and the development of pancreatitis in the later phase in this model [12].
• The objective of this study was to assess the effect of L-arginine, BH(4) and the combination of two antioxidants, superoxide dismutase and catalase, on endothelium-dependent relaxations in a swine left ventricular hypertrophy model [13].
• RESULTS: There was a statistically significant increase in endothelium-dependent relaxation to serotonin and to bradykinin with methyltetrahydropterin and with superoxide dismutase plus catalase (P<0.05) but not with L-arginine compared to untreated coronary arteries from left ventricular hypertrophy animals [13].
• Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis [14].

Biological context of SOD1

• Assignment of superoxide dismutase (SOD-1) gene to chromosome No. 9 of domestic pig [15].
• Antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total glutathione concentration were determined in guinea pig lung and liver over the final period of gestation (days 50-68) and at several ages post-partum [16].
• There was evidence of oxidative stress as indicated by a 50% increase in intracellular malondialdehyde (p < 0.05), increased mRNA expression of CuZn superoxide dismutase and Mn superoxide dismutase (by 51% and 37% respectively, p < 0.01) and a 50% decrease in glutathione in 25 mmol/l D-glucose (p < 0.001) [17].
• Both superoxide dismutase and catalase inhibited oxygen consumption in 1.0 mM GSH and 0.2 mM alloxan in the presence of rPLTT [18].
• The results indicate that retroinfusion of superoxide dismutase into the great cardiac vein before reperfusion may be an effective treatment for the prevention of reperfusion injury, even in the absence of a well developed coronary collateral circulation [19].

Anatomical context of SOD1

• Immunohistochemical analysis showed colocalization of IRF1, TLR2, and SOD1 protein in macrophages and confirmed the RNA expression data [20].
• This sulfhydryl effect may be caused by generation of hydrogen peroxide, as incubation of catalase, but not superoxide dismutase, with homocysteine-treated endothelial cells prevented this reduction, whereas copper augmented the inhibitory effects of the metabolite [21].
• Superoxide dismutase, catalase, glutathione peroxidase and NAD(P)H cytochrome c reductase were quantitated in polymorphonuclear leukocytes (PMN) and alveolar macrophages (AM) obtained from guinea pigs exposed up to 90 h to 85% oxygen [22].
• They were largely abolished by adding superoxide dismutase (12 mg/100 ml) to the superfusate and completely absent if the xanthine oxidase and purine were premixed for 60 minutes before superfusing the myocardium [23].
• The ability of superoxide dismutase to inhibit the formation of methemoglobin may represent one of its functions in the mature erythrocyte [24].

Associations of SOD1 with chemical compounds

• On day 1, pigs received an i.v. infusion of a combination of antioxidants (superoxide dismutase, catalase, and N-2 mercaptopropionyl glycine; group II, n = 9), nisoldipine (group III, n = 6), or vehicle (group I [controls], n = 9) [25].
• In contrast, this endothelium-dependent relaxation was not inhibited by nitric oxide/EDRF pathway inhibitors nor inhibitors of other potential oxygen-sensitive pathways, such as indomethacin, aminotriazole, superoxide dismutase, catalase, propranolol, or ouabain [26].
• Topical application of superoxide dismutase (40 units/ml CSF) plus catalase (40 units/ml CSF) also appeared to augment the CO2 response [27].
• Under conditions in which superoxide dismutase inhibition was incomplete, catalase inhibited the reaction but mannitol had no effect [24].
• When measured promptly after its extraction, its NADPH oxidase activity was high, but there was apparent superoxide dismutase-insensitive cytochrome c reduction, probably due to direct electron transfer to the heme protein [28].

Physical interactions of SOD1

• Could cholesterol bound to haemoglobin be a missing link for the occasional inverse relationship between superoxide dismutase and glutathione peroxidase activities [29]?

Regulatory relationships of SOD1

• Pretreating cells with catalase (100 units ml-1) did not affect the rise in cyclic GMP content induced by superoxide dismutase (30 units ml-1) [30].
• Superoxide dismutase also inhibited cholesterol 7 alpha-hydroxylation in the system where superoxides were generated by enzymatic or nonenzymatic means in the absence of NADPH-generating system [31].

Other interactions of SOD1

• OxLDL-induced foam cell formation in THP-1 macrophages was associated with increased expression of IRF1 and TLR2 and decreased expression of SOD1 [20].
• Catalase and superoxide dismutase had no effect on UF-induced lipid peroxidation in fetal liver membranes [32].
• After thawing, proliferative activity, viability, steroidogenesis and apoptosis were tested; moreover, we determined heat shock protein (HSP70) production, to investigate the recovery from stress and superoxide dismutase (SOD) and catalase activity to evaluate a possible impairment of the antioxidant pathway [33].
• The attenuated relaxation of carotid arteries to acetylcholine was not affected by superoxide dismutase and was neither found in arteries exposed to IL-1 beta for only 15 minutes nor in IL-1 beta-treated arteries for 7 hours followed by a 17-hour incubation period without the cytokine [34].
• Metallothionein is absent from adult soluble supernatant and copper is associated with superoxide dismutase and a high molecular weight protein [35].

Analytical, diagnostic and therapeutic context of SOD1

• Limitation of myocardial infarct size by superoxide dismutase as an adjunct to reperfusion after different durations of coronary occlusion in the pig [1].
• In HCAs, the NAD(P)H inhibitors diphenyleneiodonium (DPI) and apocynin, and the xanthine oxidase (XO) inhibitor allopurinol, but not the superoxide dismutase (SOD) mimetic tempol or the SOD inhibitor diethyldithiocarbamate (DETCA), reduced this constriction [36].
• METHODS: Allografts or autografts were harvested serially 3-90 days after transplantation and processed for histology and immunocytochemistry for iNOS, nitrotyrosine, a marker of peroxynitrite formation, and superoxide dismutase (SOD) [37].
• To assess the effect of cold preservation and/or ischemia reperfusion, we intravenously injected a superoxide-dismutase mimetic (EUK-134) just before transplantation of a cold-preserved XG [38].
• A superoxide dismutase C mutant of Haemophilus ducreyi is virulent in human volunteers [39].

References