Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Among the organoselenium compounds, 1,4-phenylenebis(methylene) selenocyanate (p-XSC) is reported to exert the most effective chemopreventive effect on chemically induced carcinogenesis in the mammary glands, colon, and lung of laboratory animals. This study was designed to test the inhibitory effects of dietary p-XSC (5 and 15 ppm as selenium) during the initiation phase (1 week before, during, and up to 1 week after the carcinogen exposure) and the postinitiation phase (1 week after carcinogen administration until termination) on the formation of neoplasms of the tongue induced in male F344 rats by 4-nitroquinoline-1-oxide (4-NQO). The doses of p-XSC were 20% (5 ppm selenium) and 60% (15 ppm selenium) of maximum tolerated dose levels. At 6 weeks of age, all rats except those given p-XSC alone and those in untreated groups were treated with 4-NQO (20 ppm in the drinking water for 8 weeks). Dietary p-XSC, administered at selenium levels of 5 and 15 ppm during either the initiation or postinitiation phases, significantly reduced the incidence of carcinoma of the tongue. p-XSC was especially effective when it was administered at 15 ppm selenium during the postinitiation phase, in which case it completely inhibited the development of tongue carcinoma (from 47% in the dietary control to 0%). Glutathione S-transferase activities in the liver and tongue of rats treated with 4-NQO and p-XSC were significantly elevated compared to those in rats treated with 4-NQO alone. Similarly, quinone reductase activity was significantly elevated in the liver but decreased in the tongue (posterior portion). Such modulation by p-XSC in the phase II enzyme activities of the liver and tongue might be related to inhibition of the initiation. In addition, the expression of cell proliferation biomarkers, such as polyamine level, ornithine decarboxylase activity, 5-bromodeoxyuridin-labeling index, and argyrophilic nucleolar organizer's protein number, in the epithelium of the tongue was significantly reduced in rats that were fed thep-XSC diets compared to those who were fed the basal diet. Such alteration in cell proliferation through modulation of ornithine decarboxylase activity and polyamine biosynthesis in the tongue epithelium might be related to inhibition occurring in the postinitiation phase of carcinogenesis. The dose levels of p-XSC used induced no toxicity or alteration in body weight gain. Although the precise mechanisms of p-XSC-induced inhibition of tongue carcinogenesis remains to be elucidated, it is evident that p-XSC has powerful chemopreventive efficacy against tongue carcinogenesis.
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PMID:1,4-phenylenebis(methylene)selenocyanate exerts exceptional chemopreventive activity in rat tongue carcinogenesis. 928 63

Purified DT-diaphorase can be assayed as either dicumarol-inhibitable NAD(P)H:menadione oxidoreductase or dicumarol-inhibitable NAD(P)H:dichlorophenolindophenol reductase. Both of these methods have been utilized to assay DT-diaphorase activity in tissue and cell homogenates. When DT-diaphorase activity was measured as dicumarol-inhibitable NADPH:dichlorophenolindophenol reductase in sonicates of two cell lines previously shown to not have any measurable activity of this enzyme, no enzymatic activity was detected. However, when the water-soluble bisulfite addition product of menadione was used as the electron acceptor, an artifactual activity for DT-diaphorase was detected in these cell lines. When another cell line was assayed utilizing menadione bisulfite, an apparent activity of about three times that found with dichlorophenolindophenol was measured, and thus, may overestimate DT-diaphorase activity in cells having activity. When menadione was used in place of menadione bisulfite, an artifactual DT-diaphorase activity was also detected, but was about one-half that obtained with menadione bisulfite. Polarographic determinations of the midpoint potentials for menadione and menadione bisulfite indicated that the latter compound was easier to reduce and may account for the greater apparent DT-diaphorase activity measured with this compound.
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PMID:Measurement of dicumarol-sensitive NADPH: (menadione-cytochrome c) oxidoreductase activity results in an artifactual assay of DT-diaphorase in cell sonicates. 932 55

Rabbits given 1 ppm of vanadate in drinking water for twelve months showed (a) increased plasma levels of catecholamines (b) reduction of the arterial concentration of nitric oxide (c) lower activity of urine kallikrein and higher activities of urine kininases I and II and enkephalinase (d) reduced cardiac inotropism and augmented total peripheral resistance, with unchanged blood pressure levels (e) accumulation of the metal in the aorta and cardiac ventricles. Monoaminooxidase and glucose-6-phosphate dehydrogenase activities were increased by vanadate in both kidney and liver and that of NADH-diaphorase in the kidney, in which NADPH-diaphorase activity was reduced. Some of the above results were also obtained in rats given 10 and 40 ppm of vanadate in drinking water for six-seven months; these animals showed arterial hypertension and reduced activity of Na, K-ATPase in the kidney. Vanadium appears to act on the cardiovascular function through selective neurohumoral, autacoidal and transductional mechanisms only in part depending on the species.
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PMID:[Neurohumoral, autacoid and transductional mechanisms in the cardiovascular effects of vanadate: histochemical correlations]. 937 36

The distribution of immunoreactivity to neuronal nitric oxide synthase (nNOS) and vasopressin (AVP) was studied in the circumventricular organs of the female rat. The occurrence of NOS immunoreactivity showed correspondence to nicotinamide dinucleotide phosphate diaphorase reactivity, a previously used but less specific marker for neuronal NOS. nNOS immunolabeling was detected in the two most rostrally located circumventricular organs - the organum vasculosum of the lamina terminalis and the subfornical organ. In the latter, AVP immunoreactivity was observed in some cell bodies, which also were nNOS-immunoreactive. In the median eminence and the neurohypophysis there were large amounts of nNOS- and AVP-immunoreactive nerve fibers, which often displayed similarities in distribution and morphology. Within the pineal gland, only very few nNOS-immunoreactive varicose terminals were observed, which ran along blood vessels. nNOS immunoreactivity was also seen in the epithelium of the choroid plexus, whereas no nNOS immunoreactivity could be found in the subcommissural organ or in the area postrema. The present demonstration of nNOS and AVP immunoreactivity in the subfornical organ, median eminence, and neurohypophysis, and the occurrence of nNOS immunoreactivity also in the choroid plexus and organum vasculosum of the lamina terminalis, provides a morphological background for a functional role for nitric oxide in water homeostatic mechanisms, both as executed through the hypothalamohypophyseal system and via the production of cerebrospinal fluid.
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PMID:Nitric oxide synthase and vasopressin in rat circumventricular organs. An immunohistochemical study. 938 4

The modifying effects of citrus auraptene given during the initiation and post-initiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. At 6 weeks of age, animals were divided into experimental and control groups, and fed the diets containing 100 ppm or 500 ppm auraptene. At 7 weeks of age, all animals except those treated with auraptene alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce tongue carcinoma. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing auraptene (100 and 500 ppm) for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets mixed with auraptene (100 and 500 ppm), and maintained on these diets for 22 weeks. The other groups consisted of rats fed auraptene alone (500 ppm) or untreated rats. All rats were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index were compared among the groups. In addition, the activities of gluthathione S-transferase (GST) and quinone reductase (QR) in liver and tongue of rats gavaged various doses of auraptene (0, 200, 400 and 800 mg/kg body wt) for 5 days were assayed. Feeding of auraptene at both doses during the initiation phase caused a significant reduction in the frequency of tongue carcinoma (100 ppm auraptene, 91% reduction, P < 0.001; 500 ppm auraptene, 63% reduction, P < 0.05). When fed auraptene after 4-NQO exposure, the frequency of tongue carcinoma was also decreased (100 ppm auraptene, 100% reduction, P < 0.001; 500 ppm auraptene, 74% reduction, P < 0.01). The incidences of tongue severe dysplasia in these groups were significantly smaller than those in carcinogen controls (P < 0.05). There were no pathological alterations in rats treated with 500 ppm auraptene alone or those in an untreated control group. Dietary administration of auraptene significantly decreased BrdU-labelling index and polyamine concentrations in the oral mucosa (P < 0.05). In addition, auraptene administration significantly increased the activities of GST and QR in the liver and tongue. Although dose-dependent effect was not found, citrus auraptene is effective in inhibiting the development of oral neoplasms induced by 4-NQO. Thus, suppression by the initiation-feeding of auraptene might relate to elevation in the phase II enzymes GST and QR of the liver and tongue, and inhibition occurring during the post-initiation might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.
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PMID:Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis by citrus auraptene in rats. 952 76

In recent years, the concept of cancer chemoprevention has matured greatly. Significant reversal or suppression of premalignancy in several sites by chemopreventive agents appears achievable. This article summarizes experimental data on chemopreventive effects of tea polyphenols in different tumor bioassay systems. Tea (Camellia sinensis) is cultivated in about 30 countries, and is the most widely consumed beverage in the world. Three main commercial tea varieties--green, black, and oolong--are usually consumed, but most experimental studies demonstrating the antimutagenic and anticarcinogenic effects of tea have been conducted with water extract of green tea, or a polyphenolic fraction isolated from green tea (GTP). The majority of these studies have been conducted in a mouse skin tumor model system where tea is fed either as water extract through drinking water, or as purified GTP. GTP has been shown to exhibit antimutagenic activity in vitro, and inhibit carcinogen- as well as UV-induced skin carcinogenesis in vivo. Tea consumption has also been shown to afford protection against chemical carcinogen-induced stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon carcinogenesis in specific bioassay models. Several epicatechin derivatives (polyphenols) present in green tea have been shown to possess anticarcinogenic activity; the most active is (-)-epigallocatechin-3-gallate, which is also the major constituent of GTP. The mechanisms of tea's broad cancer chemopreventive effects are not completely understood. Several theories have been put forward, including inhibition of UV- and tumor promoter-induced ornithine decarboxylase, cyclo-oxygenase, and lipoxygenase activities, antioxidant and free radical scavenging activity; enhancement of antioxidant (glutathione peroxidase, catalase, and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of lipid peroxidation, and anti-inflammatory activity. These properties of tea polyphenols make them effective chemopreventive agents against the initiation, promotion, and progression stages of multistage carcinogenesis.
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PMID:Tea antioxidants in cancer chemoprevention. 959 Nov 94

Changes of nitric oxide (NO)-producing neurons in the brain following learning is not yet clear. In present study, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and neuronal NO synthase (nNOS) immunohistochemistry were used to detect NOS neurons in rat brain. Results demonstrated that expression of NOS neurons in dentate gyrus and frontal cortex was significantly increased after a water-rewarded spatial alternation task when compared with that after sham training. The elevated expression of NOS neurons occurred not only in the earlier memory stage, but also in the later memory stage. In addition, the expression location and cell counts of NOS neurons in dentate gyrus and frontal cortex with NADPH-d staining or nNOS immunoreactivity resembled each other, but the cell counts of NADPH-d positive neurons were a little more than those of nNOS immunoreactive neurons. The involvement of NO in the processes of spatial learning and memory is further suggested.
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PMID:Spatial learning and memory induce up-regulation of nitric oxide-producing neurons in rat brain. 972 7

NAD(P)H:quinone oxidoreductase (NQO1; DT-diaphorase) is elevated in certain tumors, such as non-small cell lung cancer (NSCLC). Compounds such as mitomycin C and streptonigrin are efficiently bioactivated by NQO1 and have been used in an enzyme-directed approach to chemotherapy. Previously, 2,5-diaziridinyl-3,6-dimethyl-1,4-benzoquinone (MeDZQ) was identified as a potential antitumor agent based on its high rate of bioactivation by human NQO1 and its selective cytotoxicity to cells containing elevated NQO1. RH1, a water-soluble analogue of MeDZQ synthesized in this work, was a better substrate for recombinant human NQO1 than the parent compound. RH1 was, correspondingly, more cytotoxic to human tumor cells expressing elevated NQO1 activity (H460 NSCLC and HT29 human colon carcinoma), as measured by 3-(4,5-dimethylthiazol-2,5-diphenyl)tetrazolium assay, than it was to cells deficient in NQO1 activity (H596 NSCLC and BE human colon carcinoma). RH1 exhibited a greater selective toxicity (ratio of IC50s in H596:H460 and BE:HT29) to cells with elevated NQO1 activity relative to MeDZQ. Additionally, we report the establishment of a stable line of BE human colon carcinoma cells transfected with wild-type human NQO1 (BE-NQ7). BE cells are devoid of NQO1 activity due to a homozygous point mutation in the NQO1 gene. In comparison to the parental cell line, RH1, MeDZQ, and mitomycin C were significantly more cytotoxic to BE-NQ7 cells (17-, 7-, and 3-fold, respectively), confirming that the presence of NQO1 is sufficient to increase cytotoxicity of these antitumor quinones. These data suggest that RH1 may be an effective NQO1-directed antitumor agent for the therapy of tumors with elevated NQO1 activity, such as NSCLC.
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PMID:A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent. 986 24

We investigated the pathophysiological role of nitric oxide synthesized by inducible nitric oxide synthase in the brain, by injecting lipopolysaccharide directly into the rat cerebral cortex/hippocampus. The levels of nitric oxide metabolites, nitrite and nitrate, began to increase in a dose-dependent manner with a 3-h lag, and reached approximately seven-fold the basal levels 8 h after the direct injection of lipopolysaccharide (5 microg). The lipopolysaccharide-induced increase in nitrite and nitrate levels was inhibited by treatment with the specific inducible nitric oxide synthase inhibitor aminoguanidine. The protein synthesis inhibitor cycloheximide delayed the onset of the increase in nitric oxide metabolite levels, and reduced the peak levels. Lipopolysaccharide increased Ca2+-independent, but not Ca2+-dependent, nitric oxide synthase activity in the brain. Intense nicotinamide adenine dinucleotide phosphate-diaphorase activity was observed in round cells in the vicinity of the site of injection of lipopolysaccharide 8 h after the injection. Neuronal death was observed seven days after the injection of lipopolysaccharide. Spatial memory, as assessed by performance in a water maze task and spontaneous alternation behavior in a Y-maze, was significantly impaired in rats which had had previous bilateral injections of lipopolysaccharide into the hippocampus. The lipopolysaccharide-induced neuronal death and spatial memory impairments were prevented by aminoguanidine. These results suggest that direct injection of lipopolysaccharide into the brain causes an induction of inducible nitric oxide synthase in vivo. Furthermore, it is suggested that nitric oxide produced by inducible nitric oxide synthase is responsible for the lipopolysaccharide-induced brain dysfunction.
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PMID:Brain dysfunction associated with an induction of nitric oxide synthase following an intracerebral injection of lipopolysaccharide in rats. 1005 Dec 7

A structurally diverse group of chemopreventive agents was evaluated using in vitro biomarkers of the carcinogenesis process. With cultured human bronchial epithelial (BEAS-2B) cells, sulfur-containing compounds such as 1.2-dithiole-3-thione and sulforaphane, and phenolic compounds such as caffeic acid phenethyl ester and genistein, showed potent inhibition of benzo(a)pyrene [B(a)P] metabolite-DNA binding. Phenolic compounds also demonstrated strong antioxidant activity. Most of the test compounds did not inhibit 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity with cultured mouse epidermal ME 308 cells, with the exception of sulfur-containing compounds, 1,2-dithiole-3-thione and sulforaphane, and a selenium compound, 1,4-phenylenebis (methylene)selenocyanate. With cultured Hepa 1c1c7 cells, sulforaphane and 1,2-dithiole-3-thione mediated strong induction of quinone reductase, and genistein and ursolic acid were moderate inducers. Chalcone, 1,4-phenylenebis (methylene)selenocyanate and caffeic acid phenethyl ester induced HL-60 cell differentiation. Interestingly, sulforaphane and caffeic acid phenethyl ester inhibited the total metabolism of benzo(a)pyrene with cultured BEAS-2B cells, and the distribution pattern of water-soluble metabolites was altered in comparison with the control groups. These data are suggestive of pleiotropic mechanisms that should prove beneficial when considering the chemopreventive activity of these substances. As a result, of the group of 25 agents tested, four were judged as superior cancer chemopreventive agents: caffeic acid phenethyl ester, 1,2-dithiole-3-thione, genistein, and sulforaphane.
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PMID:Modulation of in vitro biomarkers of the carcinogenic process by chemopreventive agents. 1022 22


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