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

The human hepatoma cell line Hep 3B, which has the hepatitis B virus genome, shows over 80% decrease of copper/zinc superoxide dismutase activity, over 90% decrease of manganese superoxide dismutase activity, over 70% decrease of catalase activity, absence of glutathione peroxidase and glutathione S-transferase activities, over 270-fold increase of ferritin content and 25-fold increase of total iron compared to normal autopsy liver. These conditions of low antioxidant enzyme activities and iron overload are those which support the accumulation of oxygen free-radicals and DNA damage commonly considered to be carcinogenic mechanisms.
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PMID:Antioxidant systems in tumour cells: the levels of antioxidant enzymes, ferritin, and total iron in a human hepatoma cell line. 350 92

MnSOD is an antioxidant enzyme whose decrease in activity appears involved in tumorigenesis. We had previously reported the production of a monoclonal antibody, named 35.8, against rat MnSOD. In the present paper we show that it recognizes human and mouse MnSODs, although with different detection limits. We also use the antibody for immunofluorescence studies and observed that the antibody yields a positive staining of a non-nuclear protein, in rat and human organs where high concentration of MnSOD activity have been reported, and a lack of staining in rat kidney where MnSOD activity is decreased. Two tumors, an experimental rat hepatocarcinoma and a human liver metastasis from a gastrointestinal adenocarcinoma, are found negative for immunostaining.
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PMID:Monoclonal antibody 35.8 recognizes human, mouse and rat MnSODs in western blot and immunostaining. 808 Dec

Manganese superoxide dismutase (MnSOD) is a primary antioxidant enzyme critical for maintaining normal cell function and for survival. Previously, we cloned the entire MnSOD gene, including a 0.782-kb 5' DNA sequence, from a human embryonic lung fibroblast cell line. Sequence analysis indicates that the promoter of the human MnSOD gene is TATA-less and CAAT-less, and the DNA sequence immediately upstream from the transcription start site is GC rich. To study the function and regulation of the human MnSOD promoter, we cloned a 257-bp sequence (P7) containing the transcription start site and the 5' GC-rich region. Consensus analysis and DNase I footprinting assay indicated that P7 contains multiple Sp1- and AP-2-binding sites. Deletions of the P7 sequence diminished the promoter activity and decreased the response to Sp1 protein. The first three Sp1 consensus sites were required for high promoter activity in mammalian cells and enhanced promoter activity in Drosophila Schneider Line 2 (SL2) cells. In the SL2 cells, Sp1 activated the P7 activity in a dose-dependent manner. In contrast, cotransfections with AP-2 expression vector marginally increased P7 activities in human hepatocarcinoma HepG2 cells. The results suggest that Sp1 is an important regulator for the transcriptional activities of P7, whereas AP-2 is a minor activator for P7 and competes with Sp1 for binding sites which may downregulate P7 function.
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PMID:Transcriptional regulation of the 5' proximal promoter of the human manganese superoxide dismutase gene. 983 1

We have studied the relationship between antioxidant and anticancer properties of selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). In this study we have observed an increased level of lipid peroxide (LPO) products and decreased antioxidant enzyme activities (superoxide dismutase and catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals. Selenium (Se) was supplemented either before initiation or during initiation and selection/promotion phases of hepatocarcinogenesis and was found to be effective in altering hepatic lipid peroxidation and antioxidant enzyme activities to a statistically significant level measured either in the hepatoma or in the surrounding liver tissues. These alterations inclined towards normal in a time-dependent manner on selenium supplementation. Furthermore, increased levels of lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and catalase) were also observed in distant organs of cancer-bearing rats other than the tumour-bearing site. These alterations are brought back to normal levels upon Se treatment. Our results confirm the fact that Se is particularly protective in limiting the action of DEN by its antioxidant property.
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PMID:Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidants. 1122 68

Phytoestrogens such as the soy isoflavonoid daidzein have potential health benefits. The antioxidant properties of phytoestrogens are considered to be responsible in part for their protective effects. The antioxidant enzyme (AOE) system plays an important role in the defense of cells against oxidative insults. To determine whether flavonoids can exert antioxidative effects not only directly but also indirectly by modulating the AOE system, we investigated the influence of the flavonoid daidzein on the expression of different AOE. Daidzein treatment of hepatoma H4IIE cells increased catalase mRNA expression two- to threefold. Expression levels of copper zinc superoxide dismutase (CuZnSOD) were not affected by exposure to daidzein. Manganese superoxide dismutase (MnSOD) mRNA expression levels decreased slightly and glutathione peroxidase (GPx) levels increased slightly after daidzein exposure. Changes in AOE mRNA expression levels were significant at 300 micromol/L daidzein. To elucidate the mechanisms underlying the strong increase in catalase mRNA, transfection experiments were performed. Transient transfection of hepatoma cells with reporter plasmids containing different parts of the upstream region of the catalase gene showed a significant one- to threefold increase in reporter gene activity after daidzein exposure. This indicates that daidzein can directly activate the rat catalase promoter region. Despite the increase in catalase mRNA, daidzein pretreatment of cells did not protect against oxidative stress resulting from H(2)O(2) exposure. On the contrary, daidzein itself exerted a mild oxidative stress. In conclusion, the changes in the AOE system provoked by daidzein affected the oxidant rather than the antioxidant properties of daidzein.
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PMID:The phytoestrogen daidzein affects the antioxidant enzyme system of rat hepatoma H4IIE cells. 1188 May 57

The microsomal enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase and the low density lipoprotein (LDL) receptor pathway carry out a key role on cholesterol homeostasis in eucaryotic cells. The HMG-CoA reductase is sensitive to oxidative inactivation and to phosphorylation by many kinases that are able to inactivate the protein and increase its susceptibility to proteolysis. We previously demonstrated that a calf thymus Cu,Zn SOD affects cholesterol metabolism. This protein binds with rat hepatocyte cell membrane by a specific surface membrane receptor. The involvement of Cu,Zn SOD in cholesterol metabolism is confirmed further by the presence of this antioxidant enzyme in circulating serum lipoproteins. We studied the effect of native human Cu,Zn SOD, metal-free SOD (apo SOD), and SOD-inactivated with hydrogen peroxide on cholesterol metabolism in human hepatocarcinoma HepG2 cells. Results showed that all forms of SODs used, at the concentration of 150 ng/ml, are able to affect cholesterol metabolism decreasing both HMG-CoA reductase activity and its protein levels; this inhibitory effect is accompanied by reduced cholesterol synthesis measured as [14C]acetate incorporation into [14C]cholesterol and by an increased [125I]LDL binding to HepG2 cells. Furthermore, the inhibitory effect of Cu,Zn SOD on cholesterol synthesis was completely abolished when the cells were incubated with Cu,Zn SOD in the presence of bisindoilmaleimide (BDM), an inhibitor of protein kinase C (PKC); moreover, we demonstrated that Cu,Zn SOD as well as apo SOD was able to increase PKC activity. Overall, data demonstrate that Cu,Zn SOD affects cholesterol metabolism independently from its dismutase activity and its metal content and that the inhibitory action on cholesterol synthesis is mediated by an activation of protein kinase C.
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PMID:Effect of Cu,Zn superoxide dismutase on cholesterol metabolism in human hepatocarcinoma (HepG2) cells. 1209 81

Thioredoxin reductase 2 (TrxR2), thioredoxin II (Trx II) and peroxiredoxin III (Prx III) are specifically localized in mitochondria and believed to play important roles in the regulation of cellular redox status by serving as a primary line of defense against H2O2 produced during respiration. Substantial evidence indicates that the alteration of cellular redox status is a critical factor involved in cell growth and death and results in tumorigenesis. We therefore investigated the expression of TrxR2 and Prx III in 58 paraffin-embedded hepatocellular carcinoma tissues by immunohistochemistry. The labeling indices of TrxR2 and Prx III were significantly higher in tumor tissues than in the corresponding adjacent normal tissues. In 39 (67.2%) out of 58 samples, the levels of TrxR2 expression were higher in tumor tissues than in corresponding adjacent normal tissues, while 11 samples (19.0%) showed lower expression in tumor tissues. Prx III expression was increased in tumor tissues of 23 samples (39.7%) compared to adjacent normal tissues and were decreased in 18 samples (31.0%). These results suggest that alterations in cellular redox status by enhanced expression of TrxR2 and/or Prx III might be associated with the formation and development of hepatocellular carcinomas.
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PMID:Overexpression of mitochondrial thioredoxin reductase and peroxiredoxin III in hepatocellular carcinomas. 1253 83

The flavonol quercetin shows a wide range of effects in biological systems. We investigated whether quercetin exerts its proposed antioxidant properties via the antioxidant enzyme system. Quercetin in a concentration range from 5 to 100 microM decreased manganese superoxide dismutase, glutathione peroxidase, and copper zinc superoxide dismutase mRNA expression levels each by 30-40% in rat hepatoma H4IIE cells. Catalase mRNA expression levels increased about 30% but only with the cytotoxic concentration of 100 microM. Despite the down-regulation of antioxidant enzyme mRNA expression quercetin treatment of cells induced only a mild oxidative stress. Pretreatment of H4IIE cells with quercetin even protected against an oxidative stress resulting from hydrogen peroxide exposure. In conclusion, the antioxidant capacity of quercetin was shown not to be due to the antioxidant enzyme system.
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PMID:The effect of quercetin on the mRNA expression of different antioxidant enzymes in hepatoma cells. 1275 20

Thioredoxin reductase (TrxR), a component of the thioredoxin system, including thioredoxin (Trx) and NADPH, catalyzes the transfer of electrons from NADPH to Trx, acts as a reductant of disulfide-containing proteins and participates in the defense system against oxidative stresses. In this study, the regulation pattern of TrxR in the presence of various stressful reagents was compared between Chang (human normal hepatic cell) and HepG2 (human hepatoma cell) cell lines. Aluminum chloride (0.5 mM) and zinc chloride (0.5 mM) enhanced the TrxR activity in the Chang cell line to a higher degree than in the HepG2 cell line, but cupric chloride (0.2 mM) and cadmium chloride (0.1 mM) enhanced the TrxR activity in the HepG2 cell line to a greater degree. The TrxR activities in both Chang and HepG2 cell lines were similarly induced by treatment with sodium selenite (0.02 mM) and menadione (0.5 and 1.0 mM). Lipopolysaccharide (2 micro g/m1) increased the TrxR activity upto 4.02- and 2.2-fold in the Chang and HepG2 cell lines, respectively, in time-dependent manners. Hydrogen peroxide (5 mM) markedly enhanced the TrxR activity in the HepG2 cell line, but not in the Chang cell line. NO-generating sodium nitroprusside (3.0 and 6.0 mM) induced TrxR activities in both human liver cell lines. The TrxR activity was also induced in human liver cells under limited growth conditions by serum deprivation. These results imply that the TrxR activities in normal hepatic and hepatoma cell lines are subject to different regulatory responses to various stresses.
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PMID:Differential thioredoxin reductase activity from human normal hepatic and hepatoma cell lines. 1511 98

The homeostasis of intracellular cholesterol in animal cells is highly regulated by a complex system in which the microsomal rate-limiting enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase plays a key role in cholesterol synthesis. Substantial evidence has demonstrated that the cytosolic antioxidant enzyme CuZn superoxide dismutase (SOD1) inhibits the HMG-CoA reductase activity in rat hepatocytes and in human fibroblasts by decreasing cholesterol synthesis. Although these data suggest that SOD1 exerts a physiological role in cholesterol metabolism, it is still unclear whether the decrease of HMG-CoA reductase activity is mediated by transcriptional or by posttranscriptional events. The results of the present study, obtained by one-step RT-PCR assay, demonstrated that both SOD1 and the metal-free form of enzyme (Apo SOD1) inhibit HMG-CoA reductase gene expression in hepatocarcinoma HepG2 cells, in normal human fibroblasts, and in fibroblasts of subjects affected by familiar hypercholesterolemia. Accordingly, SOD1 could be used as a potential agent in the treatment of hypercholesterolemia, even in subjects lacking a functional LDL receptor pathway.
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PMID:Modulation of 3-hydroxy-3-methylglutaryl-CoA reductase gene expression by CuZn superoxide dismutase in human fibroblasts and HepG2 cells. 1547 58


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