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)

Propionibacterium shermanii contains a single constitutive superoxide dismutase (SOD) which is active with either iron or manganese incorporated in the same protein moiety. Copper and cobalt can also be incorporated by the bacteria in the active center of the SOD under conditions of metal deficiency, but in this case the enzyme is enzymatically inactive. In contrast to other bacterial SODs, the Fe-SOD of P. shermanii remains highly resistant to inactivation by hydrogen peroxide, as does Mn-SOD. Both SOD types cannot be distinguished by their inactivation patterns. Incubation with hydrogen peroxide results in a concentration- and time-dependent decrease in tryptophan fluorescence, independent of the metal present in the active center. Moreover, the Fe-SOD shows a time-dependent decrease in spin concentration after addition of hydrogen peroxide, which reflects alterations in the environment of the metal rather than a reduction of Fe3+ to Fe2+. No obvious correlations exist, however, between these effects and the enzymatic activity of the enzyme. The resistance of the SODs from P. shermanii to inactivation by hydrogen peroxide seems to be caused by the fact that a tryptophan residue near the metal-chelating histidine-75--which is present in all Fe-SODs being rapidly inactivated by this agent--is exchanged for valine.
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PMID:Reactions of hydrogen peroxide with superoxide dismutase from Propionibacterium shermanii--an enzyme which is equally active with iron or manganese--are independent of the prosthetic metal. 808 Feb 76

This review concerns various minerals (sodium, potassium, calcium, magnesium, phosphorus), trace elements (zinc, manganese, selenium, copper, iron, cobalt, iodine, chromium, fluorine, lead, cadmium) and other biological variables (nitric oxide, L-carnitine, glutamine, serum transferrin receptor, biopyrrins) in relation to hemorheologic effects, stress, immune response and infections during physical and sports activities. In athletes, macroelements in the ionized form contribute to heart and muscle contractions, oxidative phosphorylation and the synthesis and activation of enzymatic systems. Zinc (Zn) protects against the effects of increased free reactive oxygen species such as copper (Cu) and manganese (Mn) (Cu-Zn superoxide dismutases; Mn superoxide dismutase). Selenium in glutathione peroxidase protects the cardiovascular system and the muscles, and helps combat allergic and inflammatory diseases. Copper and iron are involved in many aspects of energy metabolism and are important components in the synthesis of hemoglobin, myoglobin and cytochromes. Fluorine and Cu protect the ligaments and tendons. Physical activity appears to be beneficial to urban residents who are exposed to metal pollution (lead, cadmium). The data cited in this review are often contradictory and incomplete. It is still unclear in many cases how minerals are involved in physiological changes, and much work remains.
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PMID:Minerals, trace elements and related biological variables in athletes and during physical activity. 1158 Sep 4

Superoxide dismutases (SODs) are vital components that defend against oxidative stress through decomposition of superoxide radical. Escherichia coli contains two highly homologous SODs, a manganese- and an iron-containing enzyme (Mn-SOD and Fe-SOD, respectively). In contrast, a single Mn-SOD is present in Bacillus subtilis. In E. coli, the absence of SODs was found to be associated with an increased sensitivity to cadmium, nickel and cobalt ions. Mutants lacking either sodA or sodB exhibited metal resistance to levels comparable to that of the wild-type strain. Although sod-deficient mutant cells were more resistant to zinc than their wild-type counterpart, no differences between the strains were observed in the presence of copper. In B. subtilis, the sodA mutation had no effect on cadmium and copper resistance. These results suggest that intracellular generation of superoxide by cadmium, nickel and cobalt is toxic in E. coli. They support the participation of sod genes in its protection against metal stress.
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PMID:The manganese and iron superoxide dismutases protect Escherichia coli from heavy metal toxicity. 1176 65

Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are well recognised for playing a dual role as both deleterious and beneficial species. The "two-faced" character of ROS is substantiated by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous or exogenous insults is termed oxidative stress and is common for many types of cancer cell that are linked with altered redox regulation of cellular signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in carcinogenesis and elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural, chemical and biochemical aspects of free radicals, the endogenous and exogenous sources of their generation, the metal (iron, copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the DNA damage (both mitochondrial and nuclear), the damage to lipids and proteins by free radicals, the phenomenon of oxidative stress, cancer and the redox environment of a cell, the mechanisms of carcinogenesis and the role of signalling cascades by ROS; in particular, ROS activation of AP-1 (activator protein) and NF-kappaB (nuclear factor kappa B) signal transduction pathways, which in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) and non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin and lipoic acid), flavonoids, selenium and others) in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors, including Ref-1, NF-kappaB, AP-1 are also reviewed.
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PMID:Free radicals, metals and antioxidants in oxidative stress-induced cancer. 1643 Aug 79

It is known that cells suffer a chronic hypoxic condition during the development of proximal tubulointerstitial disease. However, it is accepted that extracellular-superoxide dismutase (EC-SOD) protects the cells from oxidative stress. The purpose of this study was to elucidate the regulation of EC-SOD expression in cells under hypoxia. The results show that the expressions of EC-SOD mRNA and protein in cobalt chloride (CoCl(2))-treated COS7 cells decreased in a dose- and time-dependent manner, whereas the expressions of other SOD isoforms (Cu/Zn-SOD and Mn-SOD) were not changed. The down-regulation of EC-SOD mRNA was suppressed by pre-treatment with the antioxidant trolox and the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB203580. It is concluded that the expression of EC-SOD is decreased through ROS and p38-MAPK signalling cascades and that the down-regulation of EC-SOD leads to a decrease in the resistance to oxidative stress of COS7 cells under hypoxia induced by CoCl(2).
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PMID:Cobalt chloride decreases EC-SOD expression through intracellular ROS generation and p38-MAPK pathways in COS7 cells. 1903 13

Endothelium-denuded bovine pulmonary arteries (BPA) contract to hypoxia through a mechanism potentially involving removing a superoxide-derived hydrogen peroxide-mediated relaxation. BPA organ cultured for 24 h with 0.1 mM cobalt chloride (CoCl(2)) to increase the expression and activity of heme oxygenase-1 (HO-1) is accompanied by a decrease in 5 microM lucigenin-detectable superoxide and an increase in horseradish peroxidase-luminol detectable peroxide levels. Force development to KCl in BPA was not affected by increases in HO-1, but the hypoxic pulmonary vasoconstriction (HPV) response was decreased. Organ culture with a HO-1 inhibitor (10 microM chromium mesoporphyrin) reversed the effects of HO-1 on HPV and peroxide. Treatment of HO-1-induced BPA with extracellular catalase resulted in reversal of the attenuation of HPV without affecting the force development to KCl. Increasing intracellular peroxide scavenging with 0.1 mM ebselen increased force development to KCl and partially reversed the decrease in HPV seen on induction of HO-1. HO-1 induction increases extracellular (ec) superoxide dismutase (SOD) expression without changing Cu,Zn-SOD and Mn-SOD levels. HO-1-induced BPA rings treated with the copper chelator 10 mM diethyldithiocarbamate to inactivate ecSOD and Cu,Zn-SOD showed increased superoxide and decreased peroxide to levels equal to non-HO-1-induced rings, whereas the addition of SOD to freshly isolated BPA rings attenuated HPV similar to HO-1 induction with CoCl(2). Therefore, HO-1 induction in BPA increases ecSOD expression associated with enhanced generation of peroxide in amounts that may not be adequately removed during hypoxia, leading to an attenuation of HPV.
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PMID:Heme oxygenase-1 induction modulates hypoxic pulmonary vasoconstriction through upregulation of ecSOD. 1966 46