UNIPROT:P04179 - FACTA Search

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Query: UNIPROT:P04179 (MnSOD)
2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive oxygen species such as superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxy radical (OH) possess potent oxygen toxicity to cells. Superoxide dismutases (SODs) are metalloenzymes that are essential for dismutation of O2- to H2O2 and O2. SODs are important initial components in the cellular defense against oxygen toxicity since O2- can react with H2O2 to generate single oxygen and hydroxy radicals, which are even more reactive and cytotoxic than O2- or H2O2. In mammalian tissues three superoxide dismutases (SODs) designated Cu,Zn-SOD, Mn-SOD and extracellular SOD exist. These enzymes play an important role in the antioxidant defense system against superoxide anion (O2-) generated in vivo and may be involved in various pathophysiological processes including inflammation, cancer diabetes, aging and ischemia. (1) The role of superoxide anion in ovulation and luteal function was investigated the localization of Cu, Zn-SOD and Mn-SOD in rat and human ovary by immunohistochemical methods. Cu,Zn-SOD was present in granulosa cells of mature Graafian follicles and growing follicles and Mn-SOD was present in luteal cells of the corpus luteum in rat. (2) To investigate the relationship between active oxygen radical-scavenge system and ovulatory mechanism in human. Mn-SOD was found in granulosa cells and theca cells of mature follicles, luteal cells of corpus luteum and epithelial cells of fallopian tubes. Cu,Zn-SOD was localized in theca cells of mature follicles, margin of corpus luteum and epithelial cells of tubal isthmus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Oxygen radicals-superoxide dismutase system and reproduction medicine]. 837 Oct 13

Saccharomyces cerevisiae aBR10 cells are able to develop resistance to lethal ethanol concentrations (14%, v/v), by preexposure to a sublethal heat shock (37 degrees C) or ethanol stress (8%, v/v). Heat shock and 8% ethanol stress had no effect on the concentrations of glutathione [reduced (GSH) and oxidized (GSSG) forms] and on glutathione reductase and CuZn superoxide dismutase (SOD) activities, suggesting that the development of resistance to lethal ethanol concentrations is independent of these antioxidant defenses. In fact, a S. cerevisiae mutant, deficient in CuZnSOD, had an even higher ethanol tolerance, compared to the wild-type strain, and this mutation did not impair a further acquisition of ethanol tolerance. In contrast to CuZnSOD, the MnSOD activity seems to play a more important role in ethanol resistance. The MnSOD activity of the S. cerevisiae aBR10 cells increased upon exposure to heat shock or 8% ethanol. The higher tolerance to 14% ethanol in CuZnSOD deficient cells was also associated to a higher MnSOD activity, as compared to the aBR10 cells; this activity decreased during both stress pretreatments (while still higher than that observed in the wild-type strain). The results obtained suggest that maximum ethanol tolerance is attained with a MnSOD activity close to 1.0 U/mg protein. On either side of this value, the increased sensitivity of S. cerevisiae cells to 14% ethanol might be due to an inability to prevent either superoxide radical- or hydrogen peroxide-induced damages, respectively. These results are supported by the fact that a MnSOD deficiency renders yeast cells more ethanol sensitive.
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PMID:Acquisition of ethanol tolerance in Saccharomyces cerevisiae: the key role of the mitochondrial superoxide dismutase. 843 41

Superoxide dismutases (SODs) are metalloenzymes that detoxify superoxide radicals, and occur in cytosolic (Cu,Zn-SOD) and mitochondrial (Mn-SOD) forms in multiple tissues, including brain. A neuroprotective effect against oxide stressor exposures may be provided by SOD, although excessive enzyme activity can produce cell injury by formation of hydroxyl radical from hydrogen peroxide. We measured Cu,Zn-SOD and Mn-SOD activities in peripheral lymphocytes of 43 newly diagnosed idiopathic Parkinson's disease (PD) cases and 62 age- and sex-matched controls free of neurodegenerative disorders. Significant excesses of both SOD forms were found among PD cases compared with controls; however, the excesses were found exclusively among PD patients treated with the monoamine oxidase inhibitor selegiline (L-deprenyl). Enzyme-linked immunosorbent assays (ELISAs) confirmed that the activity excesses were due to increased protein rather than more highly reactive enzymes in lymphocytes of PD cases. Our findings clearly indicate the importance of selegiline on measured Cu,Zn-SOD and Mn-SOD activity in peripheral lymphocytes. Characterizing a possible therapeutic value of SOD will require longitudinal assessments of SOD in relation to PD progression.
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PMID:Selegiline and lymphocyte superoxide dismutase activities in Parkinson's disease. 860 57

To investigate the possible role of the superoxide radical and its scavenging system in the human endometrium, the immunohistochemical distribution of superoxide dismutase (SOD), activities of SOD and lipid peroxide concentrations were studied in the human endometrium throughout the menstrual cycle and in early pregnancy. The endometrial epithelium showed a positive immunostaining for Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycle and in early pregnancy. In the stroma, weak immunostaining for Cu,Zn-SOD and moderate immunostaining for Mn-SOD were observed in the predecidual cells in the late secretory phase. Decidual cells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the mid-secretory phase, and decreased in the late secretory phase. The total SOD activity in the endometrium of of early pregnancy was the same level as that in the mid-secretory phase. Cu,Zn-SOD and Mn-SOD activities changed in a similar manner to total SOD activity throughout the menstrual cycle and in early pregnancy. Lipid peroxide concentration in the endometrium increased from early proliferative phase to mid-late proliferative phase and further increased in the late secretory phase. However, lipid peroxide concentration in the endometrium of early pregnancy was the same as that in the mid-secretory phase. These results suggested that the superoxide radical and its scavenging system may play an important role in the regulation of human endometrial function.
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PMID:Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy. 867 93

Superoxide dismutases (SODs) protect cells from damage by oxygen free radicals. Manganese (Mn) SOD is preferentially induced in terminally differentiating cells; induction of copper-zinc (CuZn) SOD is more closely associated with postnatal exposure to environmental sources of oxygen free radicals. The purpose of this study was to investigate ontogenetic changes in immunoreactivity for MnSOD and CuZnSOD relative to the expression of markers of neuronal and chemosensory differentiation in olfactory and vomeronasal receptor neurons (ORNs and VRNs, respectively), which mature with different time courses. Immunoreactivity for both SODs was detected in rat ORNs at embryonic day (E) 14, the earliest time point investigated, but not until E16 in vomeronasal neuroblasts. ORNs also expressed the neuronal marker protein gene product (PGP) 9.5 and the chemosensory cell marker olfactory marker protein (OMP) at E14; vomeronasal neuroblasts expressed PGP 9.5 at E16 but were not immunoreactive for OMP until postnatal day (P) 2. Immunoreactivity for MnSOD in ORNs and VRNs generally increased pre- and postnatally to a maximum at P11. Immunoreactivity for CuZnSOD did not increase markedly until after birth, reaching maximal levels at P11-P24. Within ORNs and VRNs, the most intense immunoreactivity was localized in the dendritic and supranuclear regions. The results indicate that in ORNs and VRNs, increases in MnSOD immunoreactivity during ontogeny parallel the ongoing differentiation and maturation of chemosensory receptor neurons; in contrast, the induction of immunoreactivity for CuZnSOD is associated with postnatal exposure to the ambient oxygen and xenobiotic environment.
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PMID:Differential expression of manganese and copper-zinc superoxide dismutases in the olfactory and vomeronasal receptor neurons of rats during ontogeny. 908 17

Tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide, SR 4233, WIN 59075) is a bioreductive antitumor agent with a high selective toxicity for hypoxic cells. The selective hypoxic toxicity of TPZ results from the rapid reoxidation of the one-electron reduction product, the TPZ radical, in the presence of molecular oxygen with the concomitant production of superoxide radical. Under hypoxia the TPZ radical kills cells by causing DNA double-strand breaks and chromosome aberrations. However, the mechanism of aerobic cytotoxicity is still a matter of debate. In this study, we investigated the mechanism of aerobic cytotoxicity by adapting human lung adenocarcinoma A549 cells to aerobic TPZ exposure and characterizing the changes associated with drug resistance. The adapted cells were resistant to aerobic TPZ exposures (with dose-modifying factors of up to 9.2), although hypoxic sensitivity was largely unchanged. Relative to the parental A549 cell line, adaptation to continuous aerobic TPZ exposure resulted in increased levels of manganese superoxide dismutase (up to 9.4-fold), moderate increases in glutathione reductase (up to 2.1-fold), and loss of both quinone oxidoreductase (DT-diaphorase) activity and NADPH cytochrome P450 reductase activity. There was essentially no change in the activity of the cytoplasmic form of superoxide dismutase (CuZnSOD), catalase, or glutathione peroxidase. The increased activity of antioxidant enzymes in the resistant cell lines (in particular MnSOD) strongly suggests that reactive oxygen species are, in large part, responsible for the toxicity of TPZ under aerobic conditions, and is consistent with aerobic and hypoxic drug cytotoxicity resulting from different mechanisms.
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PMID:Adaptation of human tumor cells to tirapazamine under aerobic conditions: implications of increased antioxidant enzyme activity to mechanism of aerobic cytotoxicity. 927 29

The enzyme superoxide dismutase (SOD), which catalyzes the dismutation of the superoxide radical, is present in the cytosol and mitochondria of all oxygen-respiring eukaryotes. The cytosolic form contains copper and zinc (CuZnSOD), whereas the mitochondrial form contains manganese (MnSOD). The latter protein is synthesized in the cytosol as a MnSOD precursor, containing an N-terminal mitochondrial-targeting sequence. CuZnSOD is sensitive toward cyanide (CN) and hydrogen peroxide (H2O2), but MnSOD is not. Assays for SOD activity in cytosol from the hepatopancreas of the blue crab, Callinectes sapidus, showed the presence of a CN/H2O2-insensitive form of SOD. No CN/H2O2-sensitive CuZnSOD was found. This unexpected phenomenon was shown to occur in all decapod crustacea (crabs, lobsters, shrimp) examined. The cytosolic and mitochondrial SODs of C. sapidus were purified by means of ion-exchange, size-exclusion, and reverse-phase HPLC. The cytosolic SOD is a homodimeric protein, which exists in a monomer-dimer equilibrium (24 kDa left and right arrow 48 kDa). The protein contains approximately 1 Mn per subunit. No copper or zinc is present. Amino acid sequence analysis identified the novel cytosolic SOD as a MnSOD precursor with an abnormal mitochondrial-targeting sequence. The mitochondrial SOD of C. sapidus is similar to the MnSOD found in other eukaryotes. N-Terminal amino sequences of mitochondrial and cytosolic blue crab MnSOD differ in several positions. The MnSODs are thus encoded for by two different genes. The paradigm that all eukaryotes contain intracellular CuZnSOD and that MnSOD occurs exclusively in the mitochondria appears not to apply to a large group of marine arthropods.
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PMID:The paradigm that all oxygen-respiring eukaryotes have cytosolic CuZn-superoxide dismutase and that Mn-superoxide dismutase is localized to the mitochondria does not apply to a large group of marine arthropods. 934 Dec 31

Involvement of the superoxide radical in impaired relaxation of penile cavernous smooth muscle in hypercholesterolemia was investigated. New Zealand White rabbits (n = 40) were randomly divided into control and treatment groups. The control group (n = 20) received a regular diet while the treatment group (n = 20) was fed a diet of 2% cholesterol for 8 weeks. Blood level of cholesterol in the cholesterol-fed group was significantly higher than that of the control group. The contraction responses of cavernous tissues to norepinephrine were not significantly different in the two groups. The relaxation responses to endothelium-dependent agents (acetylcholine, bradykinin) were significantly reduced in the hypercholesterolemic group compared with the control group. However, the relaxation responses to endothelium-independent agents (papaverine, verapamil) were not significantly different in the two groups. The production of superoxide radicals was significantly higher in the hypercholesterolemic group than in the control group (P < 0.01). The activity of superoxide dismutase (total SOD, Mn-SOD, Cu,Zn-SOD) increased significantly in the hypercholesterolemic group compared with the control group (P < 0.05). The activities of catalase and glutathione peroxidase also increased in the hypercholesterolemic group, but were not significantly higher than those of the control group. Therefore, production of the superoxide radicals in rabbit cavernous tissues increases in the state of hypercholesterolemia, which may lead to functional impairment of cavernous smooth muscle relaxation in response to endothelium-mediated stimuli.
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PMID:Involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits. 937 15

Superoxide radicals may exert both toxic and physiological regulating actions on spermatozoa. The objective of the present study was to examine the occurrence and distribution of the three superoxide dismutase (SOD) isoenzymes in human seminal plasma and spermatozoa. Human seminal plasma has previously been reported to possess high SOD activity. Here we show that the normally cytosolic CuZn-SOD remarkably accounts for 75% of the activity while the secretory extracellular SOD (EC-SOD) accounts for 25%. Studies of split ejaculates suggest that both these SOD isoenzymes are of primarily prostatic origin. The Mn-SOD activity was negligible. The total SOD activity of seminal plasma was 20 times higher than that of human blood plasma. While native EC-SOD shows high affinity for heparin and heparan sulphate, 90% of the EC-SOD in seminal plasma lacks the high affinity at ejaculation. Thus only a minor part of the seminal plasma EC-SOD has the potential to bind to cell surfaces. Human spermatozoa were found to contain exceptionally large amounts of CuZn-SOD. There was little Mn-SOD activity and the amount of EC-SOD was negligible. We conclude that spermatozoa in semen are exceptionally well protected against superoxide radicals both internally and externally. This should be of importance for both their survival and the integrity of DNA, and may also have physiological effects such as influencing capacitation.
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PMID:Superoxide dismutase isoenzymes in human seminal plasma and spermatozoa. 946 51

There are two types of homologous enzymes catalysing the dismutation of the superoxide radical--Cu-Zn superoxide dismutases, and manganese or iron superoxide dismutases. In the latter two forms there is a high percentage of identity in the primary structures, and the tertiary structures are very similar particularly in the areas of the active site and in the residues responsible for the formation of the dimer. The quaternary structure of the dimer is also highly conserved. However, it has been found that despite this conservation there is strong metal ion specificity and many enzymes in the family will only be active if the correct metal ion is present. The purpose of this study has been to analyse solved X-ray structures for interactions common in both the manganese and iron forms and those that are specific to each, which may indicate reasons for the metal ion specificity. Initial analysis points to the probability that it is a combination of a number of residues, and not necessarily the same ones in every instance, which confer the specificity. In addition we have identified some anomalies in the currently available Fe/MnSOD structures which may require further remodelling and refinement.
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PMID:An analysis of structural similarity in the iron and manganese superoxide dismutases based on known structures and sequences. 954 69

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