Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antioxidant enzymes in parasites play an important role in protection against the oxygen radicals by generating during aerobic metabolism, as well as in defence against host immune cell assault. Here we report the cloning and characterisation of a cDNA encoding peroxiredoxin from Ascaris suum (AsPrx). AsPrx is 776bp long and contains the nematode 22bp splice leader sequence at the 5' end and polyadenylation signal followed by poly(A) tail at the 3' end. AsPrx codes a full-length protein with a predicted molecular mass of 22. 6kDa, and possesses two cysteine residues at amino acid 49 and 168 that are conserved among Prx proteins. GenBank() analysis showed that the deduced amino acid sequence had significant similarity to parasite and mammalian Prx at the amino acid level. DNA nicking revealed that Escherichia coli-expressed recombinant AsPrx (rAsPrx) is enzymatically inhibited to form oxidative-nicking of supercoiled plasmid DNA. Two-dimensional immunoblot analysis with mouse anti-rAsPrx serum reacted two major constituent protein spots in extracts of adult female worms, suggesting that the native AsPrx might be function as a major antioxidant enzyme in Ascaris suum.
 ...
PMID:Cloning and characterisation of a peroxiredoxin from the swine roundworm Ascaris suum. 1070 94

The artificially induced rat deciduoma serves as a model to study cellular changes associated with implantation in the endometrium. The stromal cells differentiate to form two types of decidual cells and are restricted to specific anatomical sites of the uterus. Programmed cell death starts in the antimesometrial area and expression of glutathione-S-transferase, an antioxidant enzyme, enhances in these cells as the deciduoma enters the regressive phase. The enzyme activity is significantly high compared with that of mesometrial decidual cells. Similarly, lipid peroxide content of antimesometrial decidual cells is high during this phase. DNA fragmentation, a feature of cells undergoing programmed cell death, is initiated in the antimesometrial area during regression of deciduoma.
 ...
PMID:Apoptosis of rat decidual cells: site specific initiation and related biochemical changes. 1070 22

In the present study we investigated on cultures of hepatocytes from phenobarbital-pretreated rats, the effect of the antioxidants, 0.5 mM N-acetylcysteine (NAC) or 1.5 mM deferoxamine (DFO), previously incubated for 24 h and coincubated with cocaine (0-1000 microM) for another 24 h. Cocaine cytotoxicity was monitored by either the lysis of the cell membranes or apoptosis. Lysis of the cell membranes was evidenced by lactate dehydrogenase leakage, apoptosis was observed by detecting a hypodiploid peak (<2C) in DNA histograms obtained by flow cytometry, peroxide production was quantified with 2', 7'-dichlorodihydrofluorescein diacetate and gene expression of the antioxidant enzymes: Mn- and Cu,Zn-superoxide dismutases, catalase and glutathione peroxidase were measured by Northern blot analysis. NAC and DFO significantly decreased the extent of lysis of cell membranes and apoptosis, and the antiapoptotic effect was parallel to peroxide generation. By the effect of NAC and DFO, significant increases were detected in the levels of mRNA of catalase, manganese superoxide dismutase and glutathione peroxidase. From these results we conclude that NAC or DFO, when incubated in the presence of cocaine, exerted a protective effect against cocaine toxicity at the level of both lysis of the membranes and apoptosis. This protective effect, in the case of NAC, was directed towards an increase in antioxidant enzyme expression, and in the case of DFO against reactive oxygen species generation.
 ...
PMID:Effect of N-acetylcysteine and deferoxamine on endogenous antioxidant defense system gene expression in a rat hepatocyte model of cocaine cytotoxicity. 1077 Oct 87

The cytostatic Adriamycin and the herbicide paraquat form reactive oxygen species during enzymatic activation. Adriamycin, but not paraquat, is also able to intercalate into DNA and to interfere with DNA synthesis and transcription. We investigated the influence of both substances on antioxidant enzyme expression in primary rat hepatocytes. Treatment of hepatocytes with Adriamycin led to an increase in catalase and a decrease in MnSOD mRNA expression. In contrast, exposure of hepatocytes to paraquat resulted in an increase in both catalase and MnSOD message levels. CuZnSOD mRNA was not responsive to either treatment. Adriamycin almost completely inhibited RNA synthesis, but paraquat did not change either RNA or protein synthesis. Both substances induced lipid peroxidation as measured by the accumulation of malondialdehyde in the medium. These findings indicate that catalase and MnSOD are not regulated coordinately in hepatocytes and that ROS-producing agents can differentially influence expression of antioxidant enzymes depending on their capacity to inhibit transcription.
 ...
PMID:Influence of Adriamycin and paraquat on antioxidant enzyme expression in primary rat hepatocytes. 1095 98

Thioredoxin, thioredoxin reductase and NADPH, the thioredoxin system, is ubiquitous from Archea to man. Thioredoxins, with a dithiol/disulfide active site (CGPC) are the major cellular protein disulfide reductases; they therefore also serve as electron donors for enzymes such as ribonucleotide reductases, thioredoxin peroxidases (peroxiredoxins) and methionine sulfoxide reductases. Glutaredoxins catalyze glutathione-disulfide oxidoreductions overlapping the functions of thioredoxins and using electrons from NADPH via glutathione reductase. Thioredoxin isoforms are present in most organisms and mitochondria have a separate thioredoxin system. Plants have chloroplast thioredoxins, which via ferredoxin-thioredoxin reductase regulates photosynthetic enzymes by light. Thioredoxins are critical for redox regulation of protein function and signaling via thiol redox control. A growing number of transcription factors including NF-kappaB or the Ref-1-dependent AP1 require thioredoxin reduction for DNA binding. The cytosolic mammalian thioredoxin, lack of which is embryonically lethal, has numerous functions in defense against oxidative stress, control of growth and apoptosis, but is also secreted and has co-cytokine and chemokine activities. Thioredoxin reductase is a specific dimeric 70-kDa flavoprotein in bacteria, fungi and plants with a redox active site disulfide/dithiol. In contrast, thioredoxin reductases of higher eukaryotes are larger (112-130 kDa), selenium-dependent dimeric flavoproteins with a broad substrate specificity that also reduce nondisulfide substrates such as hydroperoxides, vitamin C or selenite. All mammalian thioredoxin reductase isozymes are homologous to glutathione reductase and contain a conserved C-terminal elongation with a cysteine-selenocysteine sequence forming a redox-active selenenylsulfide/selenolthiol active site and are inhibited by goldthioglucose (aurothioglucose) and other clinically used drugs.
 ...
PMID:Physiological functions of thioredoxin and thioredoxin reductase. 1101 61

Decreases in stratospheric ozone levels from anthropogenic inputs of chlorinated fluorocarbons have resulted in an increased amount of harmful ultraviolet-B (UVB, 290-320 nm) radiation reaching the sea surface in temperate latitudes (30-50 degrees N). In the Gulf of Maine, present-day irradiances of ultraviolet-A (UVA, 320-400 nm) radiation can penetrate to depths of 23 m and UVB radiation can penetrate to depths of 7-12 m, where the rapidly developing embryos and larvae of the Atlantic cod (Gadus morhua) are known to occur. Laboratory exposures of embryos and larvae of Atlantic cod to ultraviolet radiation (UVR) equivalent to a depth of approximately 10 m in the Gulf of Maine resulted in significant mortality of developing embryos and a decrease in standard length at hatching for yolk-sac larvae. Larvae at the end of the experimental period also had lower concentrations of UVR-absorbing compounds and exhibited significantly greater damage to their DNA, measured as cyclobutane pyrimidine dimer formation, after exposure to UVB radiation. Larvae exposed to UVB radiation also exhibited significantly higher activities and protein concentrations of the antioxidant enzyme superoxide dismutase and significantly higher concentrations of the transcriptional activator p53. p53 is expressed in response to DNA damage and can result in cellular growth arrest in the G1- to S-phase of the cell cycle or to programmed cell death (apoptosis). Cellular death caused by apoptosis is the most likely cause of mortality in embryos and larvae in these laboratory experiments, while the smaller size at hatching in those larvae that survived is caused by permanent cellular growth arrest in response to DNA damage. In addition, the sub-lethal energetic costs of repairing DNA damage or responding to oxidative stress may also contribute to poor individual performance in surviving larvae that could also lead to increases in mortality. The irradiances of UVB radiation that elicit these responses in cod larvae can occur in many temperate latitudes, where these ecologically and commercially important fish are known to spawn, and may contribute to the high mortality of cod embryos and larvae in their natural environment.
 ...
PMID:Oxidative stress, DNA damage and p53 expression in the larvae of atlantic cod (Gadus morhua) exposed to ultraviolet (290-400 nm) radiation. 1110 19

The mitochondrial antioxidant enzyme manganese-containing superoxide dismutase (MnSOD) functions as a tumor suppressor gene. Reconstitution of MnSOD expression in several human cancer cell lines leads to reversion of malignancy and induces a resistant phenotype to the cytotoxic effects of TNF and hyperthermia. The signaling pathways that underlie these phenotypic changes in MnSOD-overexpressing cells are unknown, although alterations in the activity of several redox-sensitive transcription factors, including AP-1 and NF-kappaB, have been observed. To determine the downstream signaling molecules involved in MnSOD-induced cell resistant phenotype, in the present study we analyzed the expression profile of several groups of genes related to stress response, DNA repair, and apoptosis, in a human breast cancer MCF-7 cell line overexpressing MnSOD (MCF+SOD). Of 588 genes examined, 5 (0.85%) were up-regulated (2-42-fold), and 11 (1.9%) were down-regulated (2-33-fold) in the MCF+SOD cells compared to the parental MCF-7 cells. The five up-regulated genes were MET, GADD153, CD9, alpha-catenin and plakoglobin. The genes with the most significant down-regulation included: vascular endothelial growth factor receptor 1, TNF-alpha converting enzyme, and interleukin-1beta. GADD153 (involved in the repair of DNA double strand breaks) showed a 33-fold increase in microarray analysis and these results were confirmed by RT-PCR. To further determine the specificity in MnSOD-induced gene regulation, MCF+SOD cells were stably transfected with an antisense MnSOD sequence whose expression was controlled by a tetracycline-inducible regulator. Expression of three up-regulated genes was measured after induction of antisense MnSOD expression. Interestingly, expression level of GADD153 but not MET or CD9 was reduced 24 h after antisense MnSOD induction. Together, these results suggest that reconstitution of MnSOD in tumor cells can specifically modulate the expression of down-stream effector genes. GADD153 and other elements observed in the MCF+SOD cells may play a key role in signaling the MnSOD-induced cell phenotypic change.
 ...
PMID:Genes regulated in human breast cancer cells overexpressing manganese-containing superoxide dismutase. 1116 72

Skin is a tissue exposed most frequently to oxidative stress from the environment in daily life. Age-related changes of oxidative damage and antioxidant enzyme activity in the skin were examined in male Fischer 344 rats aged 6 to 30 months. The contents of phosphatidylcholine hydroperoxide (PCOOH) and thiobarbituric acid-reacting substances (TBARS) increased linearly with age. The content of cholesterol hydroperoxide increased until 24 months of age and then decreased. The content of 8-oxo-2'-deoxyguanosine (8-oxodG) increased gradually with age, and was significantly higher at 30 months of age than at 6 months of age. Superoxide dismutase activity tended to decrease with age. The activities of catalase and glutathione peroxidase showed no changes with age. We examined the effect of dietary restriction on the accumulation of oxidative damage in rat skin. The increase in PCOOH content in the skin of dietary-restricted rats was suppressed until 30 months of age. The TBARS and cholesterol hydroperoxide contents in the skin of dietary-restricted rats were significantly lower than in the skin of ad libitum-fed rats, while the 8-oxodG content was somewhat lower in the dietary-restricted rats than the ad libitum-fed rats. These results indicate that oxidative damage to the lipids and DNA in rat skin increases with age and that dietary restriction delays the accumulation of oxidative damage in skin.
 ...
PMID:Age-related changes in oxidative damage to lipids and DNA in rat skin. 1124 Jan 63

Manganese superoxide dismutase (Mn-SOD) is a primary antioxidant enzyme whose expression is essential for life in oxygen. Mn-SOD has tumor suppressor activity in a wide variety of tumors and transformed cell systems. Our initial observations revealed that Mn-SOD expression was inversely correlated with expression of AP-2 transcription factors in normal human fibroblasts and their SV-40 transformed counterparts. Thus we hypothesized that AP-2 may down-regulate Mn-SOD expression. To examine the functional role of AP-2 on Mn-SOD promoter transactivation we cotransfected AP-2-deficient HepG2 cells with a human Mn-SOD promoter-reporter construct and expression vectors encoding each of the three known AP-2 family members. Our results indicated that AP-2 could significantly repress Mn-SOD promoter activity, and that this repression was both Mn-SOD promoter and AP-2-specific. The three AP-2 proteins appeared to play distinct roles in Mn-SOD gene regulation. Moreover, although all three AP-2 proteins could repress the Mn-SOD promoter, AP-2alpha and AP-2gamma were more active in this regard than AP-2beta. Transcriptional repression by AP-2 was not a general effect in this system, because another AP-2-responsive gene, c-erbB-3, was transactivated by AP-2. Repression of Mn-SOD by AP-2 was dependent on DNA binding, and expression of AP-2B, a dominant negative incapable of DNA binding, relieved the repression on Mn-SOD promoter and reactivated Mn-SOD expression in the AP-2 abundant SV40-transformed fibroblast cell line MRC-5VA. These results indicate that AP-2-mediated transcriptional repression contributes to the constitutively low expression of Mn-SOD in SV40-transformed fibroblasts and suggest a mechanism for Mn-SOD down-regulation in cancer.
 ...
PMID:A family of AP-2 proteins down-regulate manganese superoxide dismutase expression. 1127 50

Catalase is an antioxidant enzyme that plays a central role in the protection against oxidative stress through the metabolism of hydrogen peroxide. Catalase has been well studied in plants, bacteria, and mammals, but little work has been done in other vertebrate species. We have cloned the zebrafish (Danio rerio) catalase cDNA containing the complete coding region and analyzed expression by both reverse transcription polymerase chain reaction and western blot. The deduced amino acid sequence predicts a protein of 526 amino acids with both the primary DNA and amino acid sequences highly conserved among vertebrate species. The major protein-heme contact points in the catalase enzyme complex are also well conserved, although several amino acids associated with the second and third levels of the major substrate channel are not, suggesting potential differences in substrate access or specificity. The 3' flanking region of the cDNA contains a dinucleotide repeat near the termination codon consisting of a near perfect CA array that is polymorphic. The rat and mouse catalase genes also contain a CA repeat sequence in the 3' untranslated region, which, along with an adjacent 5' stem-loop structure, has previously been shown to be a site for mRNA protein binding (Clerch, 1995, Arch. Biochem. Biophys. 317 (1995) 267-274). A stem-loop structure is also predicted adjacent to the zebrafish CA repeat, suggesting a similar role in catalase gene regulation.
 ...
PMID:Molecular cloning and sequence analysis of the Danio rerio catalase gene. 1128 Dec 62


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