Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels and subcellular distribution of enzymes involved in defenses against reactive oxygen superoxide dismutase (SOD; E.C.1.15.1.1), glutathione peroxidase (GPX; E.C.1.11.1.9), catalase (CAT; E.C.1.11.1.6), and DT-diaphorase (DT; E.C.1.6.99.2) and of the conjugating enzymes glutathione transferase (GST; E.C.2.5.1.18) and p-sulphotransferase (p-ST; E.C.2.8.2.1) in the corpus luteum of ovaries from pregnant and non-pregnant pigs were investigated. In addition, non-protein thiols and glutathione reductase (GRD; E.C.1.6.4.2) were examined in the same manner. The total cytosolic activities of CAT, DT, GRD, and p-ST were significantly increased, whereas total GST activity was decreased in the pregnant corpus luteum compared to the corresponding activities in non-pregnant corpus luteum. In the case of the mitochondrial fraction from pregnant corpus luteum, GPX and GRD displayed significant increases in specific activity. Upon subfractionation of the mitochondrial fraction (i.e. mitoplast preparation), SOD activity was distributed equally between the mitoplasts and the supernatant. CAT and GPX activities were mainly recovered in the supernatant, while the major GRD activity pelleted with the mitoplasts. Microsomes from pregnant corpus luteum demonstrated increased specific GPX activity and decreased SOD activity compared to the non-pregnant corpus luteum. No differences in the non-protein thiol levels in the cytosolic, mitochondrial, or microsomal fractions from the corpus luteum were observed between non-pregnant and pregnant sows.
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PMID:Levels and subcellular distributions of detoxifying enzymes in the ovarian corpus luteum of the pregnant and non-pregnant pig. 1048 30

Male and female C57B1/6 mice were rendered vitamin A-deficient, and the effects of this deficiency on certain xenobiotic-metabolizing enzymes and defenses against oxidative stress were examined. Vitamin A deficiency significantly increased the levels of DT-diaphorase, glutathione transferase, and catalase in the hepatic cytosolic fraction from male mice (5.2-, 1.6-, and 3.5-fold, respectively), as well as from female mice (4.8-, 3.3-, and 2.4-fold, respectively). In the hepatic mitochondrial fraction (containing peroxisomes) from male animals, the activities of urate oxidase and catalase were increased 3.4- and 1.7-fold, respectively. The activity of catalase in the mitochondrial fraction from female mice was not affected by vitamin A deficiency, whereas the activity of peroxisomal urate oxidase was increased 2.9-fold. The hepatic level of ubiquinone was increased somewhat. The significance of the increases observed here is presently unclear, but it may be speculated that vitamin A and/or its metabolites are somehow involved in the down-regulation of these proteins. Another possibility is that these enzymes are increased as a result of hepatic oxidative stress caused by vitamin A deficiency. However, vitamin A deficiency had no effect on the activity of superoxide dismutase in this study, whereas the activity of glutathione peroxidase was slightly decreased (27%) in the hepatic cytosolic fraction from male mice. In addition, the hepatic level of alpha-tocopherol was decreased dramatically in the vitamin A-deficient animals.
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PMID:Effects of vitamin A deficiency on selected xenobiotic-metabolizing enzymes and defenses against oxidative stress in mouse liver. 1064 45

Parkinson's disease (PD) is a neurodegenerative syndrome for which at present no cure is available; therapy consists mainly of amelioration of the symptoms with L-Dopa and/or dopamine (DA) agonists. Development of an effective causal therapy should be focussed on preventing or at least retarding the neurodegenerative process underlying the disease. At the cellular level, PD is characterized by degeneration of neuromelanin-containing dopaminergic neurons in the substantia nigra. Neuromelanin formation is the outcome of a process generally known as DA autooxidation, a chain of oxidation reactions in which highly neurotoxic DA-quinones are produced. The level of these DA-quinones, as estimated by the occurrence of their cysteinyl conjugates, is reported to be increased in the Parkinsonian substantia nigra. Hence, stimulation of pathways implicated in the detoxication of DA-quinones in the brain may provide neuroprotection in PD. Besides their inactivation through non-enzymatic antioxidants such as ascorbic acid and glutathione, DA-quinones are efficiently inactivated enzymatically by NAD(P)H:quinone oxidoreductase (NQO) and glutathione transferase(s), both of which are expressed in the human substantia nigra. The activity of these enzymes, which belong to the group of phase II biotransformation enzymes, can be up-regulated by a large variety of compounds. These compounds, including dithiolethiones, phenolic anti-oxidants, and isothiocyanates, have been shown to be active both in vitro and in vivo. Thus, considering the role of phase II biotransformation enzymes, in particular NQO and glutathione transferase(s), in the detoxication of DA-quinones, we propose that phase II enzyme inducers warrant evaluation on their neuroprotective potential in PD.
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PMID:Drug treatment of Parkinson's disease. Time for phase II. 1070 31

This study was designed to (1) evaluate retinal lipid peroxidation in early diabetes by the method specific for free malondialdehyde and 4-hydroxyalkenals, (2) identify impaired antioxidative defense mechanisms and (3) assess if enhanced retinal oxidative stress in diabetes is prevented by the potent antioxidant, DL-alpha-lipoic acid. The groups included control and streptozotocin-diabetic rats treated with or without DL-alpha-lipoic acid (100 mg kg(-1) day(-1), i.p., for 6 weeks). All parameters were measured in individual retinae. 4-Hydroxyalkenal concentration was increased in diabetic rats (2.63+/-0.60 vs. 1.44+/-0.30 nmol/mg soluble protein in controls, P<0.01), and this increase was prevented by DL-alpha-lipoic acid (1.20+/-0.88, P<0.01 vs. untreated diabetic group). Malondialdehyde, reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were similar among the groups. Superoxide dismutase, glutathione peroxidase (GSHPx), glutathione reductase (GSSGRed) and glutathione transferase (GSHTrans) activities were decreased in diabetic rats vs. controls. Quinone reductase was upregulated in diabetic rats, whereas catalase and cytoplasmic NADH oxidase activities were unchanged. DL-alpha-Lipoic acid prevented changes in superoxide dismutase and quinone reductase activities induced by diabetes without affecting the enzymes of glutathione metabolism. In conclusion, accumulation of 4-hydroxyalkenals is an early marker of oxidative stress in the diabetic retina. Increased lipid peroxidation occurs in the absence of GSH depletion, and is prevented by DL-alpha-lipoic acid.
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PMID:Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of DL-alpha-lipoic acid. 1085 58

The ability of the naturally-occurring naphthoquinone derivatives, juglone and plumbagin, to increase tissue activities of the Phase II detoxification enzymes quinone reductase (QR) and glutathione transferase (GT) has been investigated in rats. Groups of female Sprague-Dawley rats were dosed by oral intubation on 5 consecutive days with either juglone or plumbagin at 12.5, 25, 50, 75, 100 or 125 mumoles/kg/day. The animals were then killed and the activities of QR and GT determined in tissue homogenates. The naphthoquinone derivatives had no significant effect on enzyme activities in the liver, spleen, heart, lung or urinary bladder. Increases in the activities of one or both enzymes were recorded, however, in the caecum, kidney, forestomach, duodenum, colon, glandular stomach and jejunum. The possibility that induction of Phase II enzymes could contribute to the previously-reported ability of juglone and plumbagin to protect animals against chemically-induced intestinal neoplasia is discussed.
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PMID:Induction of quinone reductase and glutathione transferase in rat tissues by juglone and plumbagin. 1090 56

The aim of the present study was to investigate the enhancing effect of dietary sugar on the development of aberrant crypt foci (ACF) in male F344 rats initiated with azoxymethane (AOM). The potential role of sugar as either a co-initiator or a promoter was investigated by giving diets high in sucrose and dextrin (61%) during either the pre-initiation, the initiation, and/or the post-initiation stage of the ACF development. The colonic cell proliferation, activity of colonic phase II enzymes, and a biomarker of lipid peroxidation were additionally examined in order to obtain information on the specific mechanisms involved in the suggested effect of sucrose and dextrin on ACF development. The number of large sized and the total number of ACF were significantly increased by feeding sucrose and dextrin in the post-initiation period. No positive association between colonic cell proliferation and ACF was seen. The level of oxidative stress in the cytosol from the proximal colon and colonic glutathione transferase and quinone reductase was not affected by the sugar treatments. The overall results from this study show that sucrose and dextrin enhance the number of preneoplastic lesions in AOM-initiated rats, and act primarily as promoters in the development of ACF.
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PMID:The influence of simple sugars and starch given during pre- or post-initiation on aberrant crypt foci in rat colon. 1136 33

Many dietary isothiocyanates (ITCs) have shown cancer chemoprotective activity in animal models. Isothiocyanates rapidly accumulate in cells of various types as glutathione conjugates, and the total intracellular accumulation levels of ITCs (area under time-concentration curve; AUC) were critical for their Phase 2 enzyme inducer activities in murine hepatoma Hepa 1c1c7 cells. Induction of Phase 2 detoxification enzymes is recognized as a major cellular defense against carcinogens and other toxic agents. In order to further define the importance of intracellular AUC of ITCs in stimulating cellular detoxification functions, we have compared the intracellular AUCs and the inducer activities of four common dietary ITCs, allyl-ITC, benzyl-ITC, phenethyl-ITC and sulforaphane [1-isothiocyanato-(4R,S)-(methylsulfinyl)butane], in mouse skin papilloma (PE) cells. When PE cells were incubated with 5 microM of each ITC for 24 h, significant elevations of glutathione content (1.8-4.3-fold), quinone reductase activity (2.1-5.4-fold) and glutathione transferase activity (0.8-1.5-fold) were observed. These elevations were closely correlated with the AUCs of the ITCs. Increasing intracellular AUC of a weaker ITC by multiple dosing also increased its inducer activity. Further studies revealed that the AUC-dependent elevation of the above elements were mediated by the DNA regulatory element EpRE/ARE. In human HepG2 cells, which were stably transfected with a reporter construct under EpRE/ARE control, the intracellular AUC of the four ITCs closely correlated with the levels of reporter gene product (green fluorescent protein). These results showed that cellular accumulation levels of ITCs determine their activity in inducing cellular detoxification capacity and suggested that the intracellular AUC might be a valuable biomarker of the Phase 2 enzyme inducer activity of ITCs.
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PMID:Total intracellular accumulation levels of dietary isothiocyanates determine their activity in elevation of cellular glutathione and induction of Phase 2 detoxification enzymes. 1175 29

There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is due to the organosulfur compounds in these vegetables and that these substances act through induction of phase II detoxification enzymes. In the present studies, we have compared the ability of diallyl sulfide, dially disulfide, and diallyl trisulfide, compounds that are derived from garlic, to increase the activity of the phase II enzymes quinone reductase and glutathione transferase in a variety of rat tissues. We have also examined the onion-derived substances, dipropyl sulfide, dipropyl disulfide, dipropenyl sulfide, and dipropenyl disulfide, under identical conditions. Diallyl trisulfide and diallyl disulfide were potent inducers of the phase II enzymes. Dipropenyl disulfide was much less active, while little effect on enzyme activity was seen in animals dosed with dipropyl disulfide. Diallyl sulfide and dipropyl sulfide were weak inducers of quinone reductase and glutathione transferase, but dipropenyl sulfide was very active, with an effect similar to that of diallyl disulfide. It is possible that diallyl disulfide and diallyl trisulfide are important in the anticancer action of garlic, while dipropenyl sulfide could be involved in the beneficial action of onions.
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PMID:Relative activities of organosulfur compounds derived from onions and garlic in increasing tissue activities of quinone reductase and glutathione transferase in rat tissues. 1196 57

o-Quinones are easily formed by oxidation of physiologically relevant catechols. These reactions mainly occur in two specialized cells, catecholaminergic neurons and melanocytes. Both types of cells are related ontogenetically, as they arise from the neural crest during the developmental differentiation. o-Quinones are used to form melanin, a protective pigment formed by different mechanisms in melanocytes and catecholaminergic neurons. However, the reactivity of these quinones makes their presence in the cytosol dangerous for the cell survival and these compounds have been proposed as degenerative and apoptotic agents. Thus, melanin-producing cells show several potential mechanisms to protect themselves against the noxious effects of o-quinones. In melanocytes, the most effective autoprotecting mechanisms are the existence of malanosomes as a confined site for melano-synthesis and the action of tyrosinase-related protein 2 (TRP2) to drive L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid minimizing the formation of 5,6-dihydroxyindole. In catecholaminergic neurons, recent data suggest that glutathione transferase (GST M2-2 isoenzyme) and macrophage migration inhibitory factor (MIF) are very effective in preventing long-lived formation of dopaminechrome and noradrenochrome, although the detoxification reactions are different (conjugation to GSH or isomerization respectively). These mechanisms are less efficient for adrenochrome, although MIF and GST M1-1 could also catalyze similar reactions using this compound as substrate. In addition, the formation of adrenochrome is still under discussion, and adrenolutin formation could contribute to deactivate its harmful effects. The contribution of D-dopachrome tautomerase to these mechanisms is yet unknown, although in contrast to MIF, that enzyme does not recognize catecholaminechromes as substrates. Diaphorase could also be protective against quinones, since this enzyme catalyzes their bielectronic reduction back to catechols, thus preventing the formation of chrome species. This activity has been described in melanocytes and neurons, so that its contribution should be further investigated. In contrast to diaphorase, cytochrome P450 reductase should not be considered a protective enzyme, since its monoelectronic reduction of quinones leads to formation of semiquinones, that is, even more noxious than the quinones.
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PMID:Neurotoxicity due to o-quinones: neuromelanin formation and possible mechanisms for o-quinone detoxification. 1283 99

In recent years, considerable emphasis has been focused on identifying new chemopreventive agents, which could be useful for the human population. Piperine is a pure, pungent alkaloid constituent of black and long peppers (piper nigrum and piper longum), which is a most common spice used throughout the world. In the present study, we examined the protective role of piperine during experimental lung carcinogenesis with reference to its effect on DNA damage and detoxification enzyme system. The activities of detoxifying enzymes such as glutathione transferase (GST), quinone reductase (QR) and UDP-glucuronosyl transferase (UDP-GT) were found to be decreased while the hydrogen peroxide level was increased in the lung cancer bearing animals. Supplementation of piperine (50 mg/kg bwt) enhanced the detoxification enzymes and reduced DNA damage as determined by single cell electrophoresis. Furthermore, the DNA-Protein cross links which was found to be high in lung cancer bearing animals was also modulated upon supplementation with piperine. Our present results explain the understanding of unique association between anti-peroxidative effect of piperine and ultimately the capability of piperine to prevent cancer.
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PMID:Oral supplementation of piperine leads to altered phase II enzymes and reduced DNA damage and DNA-protein cross links in Benzo(a)pyrene induced experimental lung carcinogenesis. 1572 47


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