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)

Superoxide dismutases (SODs) are metalloproteins that catalyze the dismutation of superoxide radicals to hydrogen peroxide and oxygen. The enzyme is ubiquitous in aerobic organisms where it plays a major role in defense against oxygen radical-mediated toxicity. In plants, environmental adversity often leads to the increased generation of reduced oxygen species and, consequently, SOD has been proposed to be important in plant stress tolerance. Here we describe the isolation of a cDNA clone encoding a cytosolic copper/zinc SOD from Nicotiana plumbaginifolia. Using this, together with previously isolated cDNAs encoding the mitochondrial manganese SOD and the chloroplastic iron SOD as probes in RNA gel blot analyses, we have studied SOD transcript abundance during different stress conditions: in response to light, during photoinhibitory conditions (light combined with high or low temperatures), and in response to a xenobiotic stress imposed by the herbicide paraquat. Evidence is presented that iron SOD mRNA abundance increases whenever there is a chloroplast-localized oxidative stress, similar to the previous finding that manganese SOD responds to mitochondria-localized events. The diverse effects of the different stress conditions on SOD mRNA abundance thus might provide an insight into the way that each treatment affects the different subcellular compartments.
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PMID:Differential regulation of superoxide dismutases in plants exposed to environmental stress. 182 Aug 18

The effect of micronutrient stress (either deficiency or toxicity) on the expression of different superoxide dismutase isoenzymes in plants is reviewed. The induction of Fe-SOD and Mn-SOD by different metals and the potential use of the metalloenzyme system SOD for the appraisal of the micronutrient status of plants, is examined. At subcellular level, evidence for the participation of peroxisomal SOD in the molecular mechanism of plant tolerance to Cu is presented, and the activated oxygen-dependent toxicity of a xenobiotic (clofibrate) in plant peroxisomes is examined.
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PMID:Nutritional effect and expression of SODs: induction and gene expression; diagnostics; prospective protection against oxygen toxicity. 206 Aug 54

Cu/Zn-superoxide dismutase (SOD)-accelerated oxidation of the benzene metabolite 1,4-hydroquinone (HQ) results in the enhanced formation of semiquinone anion radicals, electrophilic 1,4-benzoquinone (BQ), and H202. We selected bone marrow stromal cells and phiX-174 double stranded plasmid DNA as model systems to investigate the cytotoxicity and DNA cleaving activity of the Cu/Zn-SOD-mediated activation of HQ. The addition of either Cu/Zn-SOD or Min-SOD to the primary bone marrow stromal cell cultures significantly enhanced HQ-induced cytotoxicity, which could be completely prevented by adding reduced glutathione (GSH) or dithiothreitol but not be adding catalase. Incubation of the plasmid DNA with the HQ/Cu/Zn-SOD system resulted in the induction of single- as well as double-strand breaks, which could be inhibited by catalase and the Cu(I) chelators, bathocuproinedisulfonic acid (BCS) and GSH. Although Mn-SOD could enhance HQ-induced cytotoxicity to stromal cells, the activation of HQ by Mn-SOD did not contribute to the induction of DNA strand breaks. Similar to the HQ/Cu(II) and H202/Cu(II) systems, the DNA strand breaks mediated by HQ/Cu/Zn-SOD could not be effectively inhibited by the hydroxyl radical scavengers, including dimethylsulfoxide, mannitol, and 5,5-dimethyl-1-pyrroline N-oxide, but could be protected by sodium azide. Low-temperature electron spin resonance experiments showed that incubation of Cu/Znu-SOD with HQ resulted in the release of copper from the Cu/Zn-SOD, which could be prevented by catalase. Alpha-(4-Pyridyl-1-oxide)-N-tert-butylnitrone (POBN)/spin-trapping studies demonstrated that the interaction of HQ with Cu/Zn-SOD, but not with Mn-SOD, resulted in the significant formation of POBN-CH3 adduct in the presence of dimethylsulfoxide, suggesting the production of hydroxyl radical or its equivalent from this enzyme/xenobiotic interaction. The formation of the POBN-CH3 adduct from the HQ/Cu/Zn-SOD could be inhibited by catalase, BCS or GSH, indicating the important role for H202 and Cu(I) in the production of reactive oxygen species. Addition of human myeloperoxidase to the HQ/Cu/Zn-SOD synergistically enhanced the formation of BQ from HQ. This enhancement could be abolished by catalase. Taken together, these results demonstrate that activation of HQ by either Cu/Zn-SOD or Mn-SOD results in cytotoxicity to primary bone marrow stromal cells through the formation of electrophilic BQ. Interaction of HQ with Cu/Zn-SOD causes oxidative damage to Cu/Zn-SOD, leading to the release of copper from the enzyme. The further reaction between the released copper and H202 generates reactive oxygen species that participate in the induction of strand breaks in plasmid DNA. The H202 generated from the Cu/Zn-SOD-accelerated oxidation of HQ can also be utilized by myeloperoxidase resulting in additional conversion of HQ to BQ.
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PMID:Role of Cu/Zn-superoxide dismutase in xenobiotic activation. II. Biological effects resulting from the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone. 864 80

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

The effects in fish (Sparus aurata) of dieldrin, previously reported to be an inducer of peroxisomal enzymes (Pedrajas et al., Comp. Biochem. Physiol. 115C (1996) 125-131), were compared with those of clofibrate. Although dieldrin provoked the more severe peroxisomal changes, both compounds induced oxidative stress as detected by the increased levels of microsomal thiobarbituric acid reactive substances; however the malondialdehyde (MDA) content, determined after HPLC separation of the MDA-TBA complex, was not significantly altered. These results suggest that, besides MDA, other aldehydes were formed in xenobiotic-injected fish, leading us to assess the oxidative effects of such xenobiotics by following changes in superoxide dismutase (SOD) pattern. New active SOD isoforms were detected by isoelectrofocusing in the light mitochondrial (LMF) and cytosolic (CF) fractions. Most of the new SOD bands could be reproduced in vitro by incubation of fish liver cell-free extracts with MDA. To clarify the effects of aldehydes, Cu,Zn- and Mn-SOD isoforms were purified and amino acid analysis was carried out. The new bands found in LMF and CF fractions were reproduced in vitro after incubation of pure SODs with MDA and 4-hydroxy-2-nonenal (HNE), the new SOD bands formed being coincident with the loss of Lys or His residues. Lysine residues were preferentially derivatized after treatment of Cu,Zn-SOD with MDA, but in Mn-SOD the lysine residues were modified only after treatment with MDA, while the histidine residues were modified only by HNE. No change of SOD activity was detected after MDA or HNE exposure, although at the higher aldehyde concentrations used protein aggregates were formed. Therefore, the appearance of new active SOD bands, after isoelectrofocusing separation, can be proposed as a biomarker of oxidative stress.
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PMID:Incubation of superoxide dismutase with malondialdehyde and 4-hydroxy-2-nonenal forms new active isoforms and adducts. An evaluation of xenobiotics in fish. 987 97

Despite extensive interest in the rodent nasal cavity as a target organ for toxicity, there is very limited information regarding nasal defenses against oxidative stress and xenobiotic-derived oxidants. Using immunohistochemistry, we have examined the distribution of Cu,Zn and Mn superoxide dismutase (SOD), catalase, glutathione (GSH) peroxidase, and DT-diaphorase in rat nasal tissues. In addition, we have determined the concentrations of ascorbate and alpha-tocopherol and the activities of SOD (combined Cu,Zn and Mn forms), catalase, GSH peroxidase, GSH reductase, and DT-diaphorase in nasal respiratory epithelium (RE), olfactory epithelium (OE), and in lung. Immunohistochemistry demonstrated that all four enzymes were similarly distributed, with the greatest staining intensity in dorsal-medial regions of the nasal cavity. In respiratory epithelium, ciliated columnar cells and subepithelial glands stained positively, while in olfactory tissue the enzymes were detected in the sustentacular cells and Bowman's glands. With the exception of SOD, enzyme activities were higher in RE than OE, while concentrations of ascorbate and alpha-tocopherol were higher in OE than RE. With the exception of catalase, nasal activities were either higher than or comparable to those of the lung. Thus, the rat nasal cavity appears to be well protected against oxidative damage.
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PMID:Antioxidant status of the rat nasal cavity. 1261 49

Cigarette smoking causes many chronic diseases but is a preventable risk factor in developing countries. However, it may be possible to relieve the smoke-induced damage by increasing the protective defense system. As vitamin C intake reduces smoking risk, it is recommended that smokers should take more vitamin C. However, the molecular mechanism of vitamin C intake on smokers has not been thoroughly investigated. We have found there to be suppression of smoke-induced cytochrome P-450 1A1 (CYP1A1) mRNA expression by high-dose ascorbic acid administration. Therefore, we surveyed other genes, the expressions of which were altered by the administration of high-dose ascorbic acid. As cigarette smoking increases oxidative stress, we investigated the effect on antioxidative enzyme expression. The osteogenic disorder Shionogi (ODS) rat, which lacks ascorbic acid synthesis enzyme, was administered either minimal amounts (4 mg/day, S4) or high-dose amounts (40 mg/day, S40) of ascorbic acid, and were exposed to cigarette smoke daily for 25 days. The effect on antioxidative enzymes mRNA expression in the liver was measured by competitive reverse transcription-polymerase chain reaction method (competitive RT-PCR). CuZn-superoxide dismutase (SOD), MnSOD, catalase and protein disulfide isomerase (PDI) were significantly decreased by high-dose ascorbic acid administration, and plasma glutathione peroxidase was also decreased, but not significantly. Cigarette smoke exposure slightly increased gene expression of PDI and catalase, but not significantly. The differently expressed 27 genes in the liver were found by differential display methods. From 27 genes, altered expression of plasma proteinase inhibitor, alpha-1-inhibitor III and CYP1A2 were confirmed by competitive RT-PCR. These results show that ascorbic acid intake influences gene expression of antioxidative enzymes, an ascorbic acid recycle enzyme, and xenobiotic metabolizing enzymes.
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PMID:The effect of cigarette smoke exposure and ascorbic acid intake on gene expression of antioxidant enzymes and other related enzymes in the livers and lungs of Shionogi rats with osteogenic disorders. 1270 Mar 99

Irgarol 1051 is an s-triazine herbicide formulated with Cu2O in antifouling paints. Recent studies have shown that Irgarol 1051 inhibits coral photosynthesis at environmentally relevant concentrations, consistent with its mode of action as a photosystem II inhibitor. Related toxicologic effects of this herbicide on coral cellular physiology have not yet been investigated. We used cellular diagnostics to measure changes in 18 toxicologic cellular parameters in endosymbiotic algal (dinoflagellate) and cnidarian (host) fractions of the common branching coral Madracis mirabilis associated with in vivo 8- and 24-hour exposures to a nominal initial Irgarol 1051 concentration of 10 microg L(-1). Responses measured were (1) xenobiotic response, which includes total and dinoflagellate multixenobiotic resistance (MXR), cnidarian cytochrome (CYP) P450-3 and P450-6 classes, cnidarian, and dinoflagellate glutathione-s-transferase (GST); (2) oxidative damage and response, which includes cnidarian and dinoflagellate Cu/Zn and Mn superoxide dismutase (SOD), cnidarian and dinoflagellate glutathione peroxidase (GPx), cnidarian catalase, and total protein carbonyl); (3) metabolic homeostasis, which includes chloroplast and invertebrate small heat-shock proteins (sHsp), cnidarian protoporphyrinogen oxidase IX (PPO), cnidarian ferrochelatase, and cnidarian heme oxygenase; and (4) protein metabolic condition, which includes cnidarian and dinoflagellate heat shock proteins (hsp70 and hsp60), total ubiquitin, and cnidarian ubiquitin ligase. Acute responses to Irgarol 1051 exposure included significant increases in total and dinoflagellate MXR, dinoflagellate Cu/Zn SOD, dinoflagellate chloroplast sHsp, and cnidarian PPO. Irgarol 1051 exposure resulted in decreases in cnidarian GPx, cnidarian ferrochelatase, cnidarian catalase, and cnidarian CYP 450-3 and -6 classes. Related implications of Irgarol 1051 exposure to coral cellular condition are discussed.
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PMID:Preliminary examination of short-term cellular toxicological responses of the coral Madracis mirabilis to acute Irgarol 1051 exposure. 1713 16

CYP1A sub-family represents the main form of cytochrome P450 involved in benzo[a]pyrene (B[a]P) detoxification, but there are no clear evidences about its presence in invertebrates. 7-Ethoxy resorufin O-deethylase (EROD) activity is strictly related to CYP1A presence, at the same time P450-dependent oxidative metabolism leads to reactive oxygen species (ROS) production, thought to be an important mechanism of pollutant-mediated toxicity in aquatic organisms. Superoxide dismutases (SODs), EROD and CYP1A activities and/or expressions were detected in haemocytes of pooled clams (Chamelea gallina) and cell-free haemolymph after 24 h, 7 and 12 days of exposure to 0.5 mg/L of B[a]P. After 24 h, B[a]P content was maximum in whole tissues. A 61 kDa band was recognized in haemocytes and cell-free haemolymph by polyclonal anti-fish CYP1A, while 53.5 and 63.8 kDa CYP1A immunopositive proteins were discriminate without differences of expression. Differently, EROD, MnSOD activity/expression and ECSOD expression decreased in haemocytes and haemolymph. C. gallina immune system presents an interesting response dose/time exposure of B[a]P and the 7 days condition highlights the major effects of xenobiotic action. The identification of basal EROD levels supports the possible presence of the CYP1A, never identified in C. gallina and more specifically never isolated in immune cells, as confirmed by CYP1A-immunopositive proteins identification.
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PMID:Investigation of EROD, CYP1A immunopositive proteins and SOD in haemocytes of Chamelea gallina and their role in response to B[a]P. 1884 44

Di-n-butyl phthalate (DBP), a xenobiotic, is widely used in industries as a softener for polyvinyl chloride resins. The aim of the present study was to evaluate whether DBP induces oxidative stress in testes of Wistar rats. DBP at doses of 500, 1,000 and 1,500 mg/kg b.wt. (doses below LD50) was given orally for 7 days. After 24 hrs from the last dose, the animals were killed under ether anesthesia. Nonsignificant increase in testicular weight was observed. Histological studies indicated a dose-related degeneration of germinal, Leydig and Sertoli cells along with loss of spermatozoa in the lumen. The concentrations of malondialdehyde (TBARS), lipid hydroperoxides, water-soluble antioxidant capacity, glutathione-S-transferase, catalase and trace elements-zinc and copper increased while concentrations of total protein, lipid soluble antioxidant capacity, ascorbic acid, glutathione, total superoxide dismutase (SOD), Cu-ZnSOD, MnSOD, glutathione peroxidase, glutathione reductase and metallothionein decreased at all the dose levels. The data suggests that the cellular functions were adversely affected due to impairment of spermatogenesis indicative of oxidative stress as evident by altered antioxidative defense system which appears to mediate through hypothalamo-pituitary-gonadal axis. The spectrum of changes in testes reflects its susceptibility to phthalate even at low dose with the potential to interfere with critical reproductive function.
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PMID:Dose-dependent short-term study of di-n-butyl phthalate on the testicular antioxidant system of Wistar rats. 2517 63


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