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)

A histichemical study is presented of the activity of some redox enzymes (succinate dehydrogenase, malate dehydrogenase, NAD-diaphorase and lactate dehydrogenase) in 37 cultured human glial brain tumours. The stages of cell activity at different periods of tumour cultivation and the level of their differentiation in the initial tissue were taken into consideration. The examined tumour cultures showed enzymatic cell polymorphizm. During of period of adaptation of explants, the activity of the Krebs cycle enzymes was low to increase during differentiation and proliferation of cultures. The activity of lactate dehydrogenase elevated in tumour cells from cultures of dedifferentiated astrocytomas and glioblastomas mith marked anaplasia. The activity of this enzyme increased also in the course of advanced necrobiotic changes in the tumour cells.
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PMID:[Histochemical study of the enzymatic activity of cultivated human macroglial brain tumors]. 116 47

The activity of 19 enzymes (hexokinase, glucoso-6-phosphatisomerase, alpha-glycerophosphate-, lactate-, succinate-, isocitrate-, malate-, glucoso-6-phosphate-, 6-phosphogluconate-, glutamate-, alcohol-, inosine-5'-phosphate-, guanosine-5'-monophosphate-dehydrogenase, cytochromoxidase NAD.N2- and NADP.N2-diaphorase, monoaminoxidase, alkaline and acid phosphatase) was studied comparatively in the mucosa of control rats and in tumors of the small intestine (27), and large intestine (176), induced in 41 rats percutaneously by 1,2-dimethylhydrazine. A decreased level of the enzymes of tissue respiration and Krebs cycle was found with a simultaneous increase in the activity of the enzymes of glycolysis and pentoso-monophosphate shunt. These data evidence variations in tumor metabolism consisting in oxidizing phosphorylation, being replaced by aerobic glycosis, and also reflecting an intensive proliferation of tumor cells.
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PMID:[An enzymohistochemical study of experimental tumors of the intestine]. 123 60

A study of ingestion and elimination of cells of peritoneal exudate (CPE) of mouse labeled antigens of various physico-chemical nature with a simultaneous analysis of their influence on the function of the enzymatic systems of macrophages showed that both the corpuscular (sheep erythrocytes, typhoid vaccine) and the soluble (albumin, endotoxin of S. typhi, tetanus and staphylococcus toxoid) antigens caused a unitypical reaction of the cells of monocytic phagocytic system. Thirty minutes after the administration the principal mass of labeled antigens (albumin, typhoid vaccine, sheep erythrocytes) was phagocytized by macrophages and was revealed chiefly in their phagolysosomal fraction. The greater part of radioactive material was eliminated in the course of the first 24 hours; however, some of it could be found in the macrophages for a long time. During the process of phagocytosis the activity of lysosomal (catepsin, acid phosphatase, desoxyribonuclease, beta-glucoronidase) enzymes in the macrophages decreased and the activity of redox (succinic dehydrogenase, NAD-N2-diaphorase) enzymes became intensified. A fall of catepsin activity in the CPE of mice 30 minutes after the intraperitoneal administration of the antigens was accompanied by its activation in the cells of the spleen.
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PMID:[General regularities of the macrophage reaction in the administration of various antigens and the phagocytosis of microorganisms]. 126 63

Mycotic foci were studied histochemically on various experimental models of candidiasis. NAD-H, NADP-H-diaphorase, acid phosphatase and ATPase were revealed in the fungi, the activity of these enzymes depended on the state of the fungus. Diaphorase activity in the mucous membrane epithelium falls only if it is damaged by massive invasion of pseudo-mycelium. Inhibition of the enzyme activity in the visceral foci (kidney, liver, heart) occurs only in case of pronounced destruction and is not observed at the distance from the fungi. The results do not confirm the idea of fungal secretion of mycotoxins penetrating into the surrounding tissues and damaging them.
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PMID:[Histochemical study of lesions in superficial and visceral candidiasis]. 129 70

The alkylating activity of reduced diaziquone was studied by the nitrobenzylpyridine (NBP) assay and was compared to those of the parent compound and aziridine-containing N,N',N"-triethylenethiophosphoramide (Thio-TEPA). Diaziquone (AZQ) was reduced enzymatically by 2e- using S9 cell fraction from MCF-7 cells which is rich in NAA(P)H:quinone-acceptor oxidoreductase (DT-diaphorase) (QAO) activity. One electron enzymatic reduction was performed with NADPH-cytochrome c reductase. The alkylating activity of AZQ increased 3-fold when reduced by 2e-. This increase was inhibited by dicumarol, an inhibitor of QAO. In contrast, the alkylating activity of AZQ did not increase beyond that of the parent compound when reduced by 1e- using purified NADPH-cytochrome c reductase. Similar results were obtained when AZQ was reduced chemically with borohydride (2e-) and with NADPH (1e-). Anaerobic incubations of AZQ with the S9 fraction of MCF-7 cells (2e- reduction) resulted in an increase in NBP alkylation over its aerobic counterpart (1.8-fold) while maintaining the near 3-fold increase in alkylation over untreated AZQ. In contrast, AZQ incubations with NADPH-cytochrome c reductase (1e- reduction) under the same conditions did not result in an NBP alkylation increase over untreated AZQ. These results indicate that AZQ hydroquinone is most likely the responsible species for the observed alkylation of this antitumor agent to DNA and other nucleophiles. The results also suggest that NAD(P)H:quinone-acceptor oxidoreductase is a very important enzyme in the bioactivation of AZQ.
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PMID:Reductive metabolism of diaziquone (AZQ) in the S9 fraction of MCF-7 cells. II. Enhancement of the alkylating activity of AZQ by NAD(P)H: quinone-acceptor oxidoreductase (DT-diaphorase). 130 Oct 71

The anthraquinone-based antitumour agents mitoxantrone, daunorubicin and ametantrone were found to be substrates for NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase) [QAO] isolated from rat liver. This was indicated by the stimulation of QAO-dependent NADPH oxidation by these agents. This effect followed Michaelis-Menten kinetics and was dependent on the concentration of QAO, inhibited by the specific QAO inhibitor dicumarol (15 microM) and enhanced by the QAO activators bovine serum albumin (0.01%) and Triton X-100 (0.03%). As indicated by the Vmax/Km ratio, mitoxantrone (26.53) was considerably more active than ametantrone (11.25) or daunorubicin (7.35). Metabolism of these anthraquinones was associated with the formation of superoxide anions, hydrogen peroxide and hydroxyl radicals as indicated by electron spin resonance spin trapping studies with 5,5-dimethyl-1-pyrroline-N-oxide. This is likely to be due to the slow auto-oxidation of the respective dihydroquinones in the presence of molecular oxygen. QAO needs to be considered as a possible route of bioreductive activation of these agents.
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PMID:NAD(P)H (quinone acceptor) oxidoreductase (DT-diaphorase)-mediated two-electron reduction of anthraquinone-based antitumour agents and generation of hydroxyl radicals. 131 84

Characteristics of DT diaphorase (NAD(P)H: (quinone acceptor) oxidoreductase, DTD) activity in Ictalurus punctatus and the effect of DTD activity on menadione (MND)-mediated reduction of acetylated cytochrome c (AcC) were examined. DTD activity in cytosols of four organs followed a distinct gradient in the order stomach greater than gill greater than liver greater than posterior kidney. A similar gradient was observed in organ-specific rates of in vitro AcC reduction in the presence of either NADH or NADPH as reducing equivalent. A greater proportion of the AcC reduction rate was sensitive to inhibition by dicoumarol (DC) in organs with relatively high DTD specific activity (e.g., stomach) than in organs with low DTD activity (e.g., kidney). No such trend was observed in the superoxide dismutase (SOD)-sensitive proportion of AcC reduction rates. DTD was observed to contribute to MND-mediated superoxide production to a greater extent in organs with high DTD activity than in organs with low DTD activity. DC-sensitive (i.e., DTD-mediated) AcC reduction was observed to increase with organ-specific DTD activity, and the majority of the AcC reduction rate was inhibitable by SOD. These findings demonstrate a direct contribution by DTD activity to MND-mediated superoxide production in this in vitro system. The role of I. punctatus DTD as a possible deleterious agent in quinone metabolism and implications regarding the traditional conception of DTD as a detoxifying enzyme are discussed.
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PMID:DT diaphorase [NAD(P)H: (quinone acceptor) oxidoreductase] facilitates redox cycling of menadione in channel catfish (Ictalurus punctatus) cytosol. 131 45

Incubation of rat liver cytosolic or microsomal fractions with chromium(VI) led to a dramatic decrease in chromium(VI) mutagenicity, as determined by the Ames Salmonella assay using the TA100 tester strain. The cytosol-dependent decrease in chromium(VI) mutagenicity was found to be counteracted in the presence of dicumarol, an inhibitor of the cytosolic enzyme NAD(P)H:quinone oxidoreductase (DT-diaphorase). In order to determine whether DT-diaphorase is a significant factor in enzymatic reduction of chromium(VI) in rat liver tissue, cytosolic and microsomal fractions were analyzed for NAD(P)H-dependent chromium (VI) reductase activity leading to chromium(V) formation by using electron paramagnetic resonance (EPR) spectroscopy. Reaction of chromium(VI) with NADH or NADPH in the presence of either cytosolic or microsomal fractions led to the formation of stable chromium(V)--NAD(P)H complexes. When glucose 6-phosphate (G6P) was present in the reaction as part of a NADPH-generating system, stable chromium(V)--G6P complexes were formed in addition to the chromium(V)--NAD(P)H complexes. The chromium(V) complexes had g values of 1.980-1.982 and superhyperfine splitting constants of 0.8-0.9 characteristic of bis(diol)oxochromium(V) complexes. Inhibition of 90% of the cytosolic DT-diaphorase activity by dicumarol led to only partial (20-22%) inhibition of chromium(V) formation. Visible and EPR spectroscopic studies showed that purified DT-diaphorase had no detectable chromium(VI) reductase activity and did not catalyze formation of chromium(V). Inhibition of 69% of microsomal aryl hydrocarbon hydroxylase activity by ketoconazole led to partial (10%) inhibition of chromium(V) formation. These results indicate that intracellular NAD(P)H-dependent enzymatic reduction of chromium(VI) in rat liver cannot be attributed to the activity of any one enzyme in the cytosolic or microsomal fractions. DT-diaphorase appears to play an indirect role in decreasing chromium(VI)-induced mutagenicity in Salmonella, possibly through interaction with other redox active cellular components. The involvement of diols such as sugars and pyridine nucleotides in stabilizing intracellularly generated chromium(V) is discussed.
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PMID:Reduction of chromium(VI) to chromium(V) by rat liver cytosolic and microsomal fractions: is DT-diaphorase involved? 137 26

The activities of NAD(P)H-dependent quinone reductase (QR) and the cytochrome P-450 monooxygenases 7-ethoxycoumarin O-deethylase (7-ECD) and 7-ethoxyresorufin O-deethylase (7-ERD) were measured in four subpopulations of murine epidermal keratinocytes (MKs) that differed in their stages of differentiation. Noninduced per cell 7-ECD and 7-ERD activities were the lowest in basal cell MKs and progressively increased as the MKs underwent differentiation. In contrast, noninduced per cell QR activities in the three less differentiated MK subpopulations were very similar to one another and greater than the activities measured in the most differentiated subpopulation. Treatment of dorsal skin with 100 nmol of dibenz[a,c]anthracene (DB[a,c]A) increased CYPIA1 mRNA abundance and elevated 7-ERD activities to similar per cell levels in all MK subpopulations. This was achieved by differential inductions (200- to greater than or equal to 1850-fold) of 7-ERD in the different subpopulations. In contrast, QR induction by DB[a,c]A was similar (less than 3-fold) in all MK subpopulations. Consequently, the expressions of noninduced QR and 7-ERD activities in skin are regulated as a function of MK differentiation. However, the distributions of the noninduced activities of these two enzymes in MK subpopulations are the exact opposite. Furthermore, the relative inducibility of 7-ERD, but not QR, in skin is also regulated as a function of epidermal differentiation.
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PMID:Differential expression of basal and hydrocarbon-induced cytochrome P-450 monooxygenase and quinone reductase activities in subpopulations of murine epidermal cells differing in their stages of differentiation. 138 68

Dicumarol, often used as a specific inhibitor of DT diaphorase (NAD(P)H:(quinone-acceptor) oxidoreductase; EC 1.6.99.2), was found to potently inhibit GSH transferases (EC 2.5.1.18). Dicumarol exhibited an IC50 of 11 microM in inhibiting the conjugation of 1-chloro-2,4-dinitrobenzene (50 microM) by GSH transferase GT-8.7, the major hepatic class mu isoenzyme of CD-1 mice. The activities of GT-8.7 and of the class pi isoenzyme, GT-9.0, toward a carcinogenic substrate, 4-nitroquinoline 1-oxide (100 microM), were inhibited by dicumarol with IC50 values of 14 and 9 microM, respectively. Dicumarol also affected GSH peroxidase II activity, inhibiting the reduction of cumene hydroperoxide by GT-10.6, the predominant class alpha GSH transferase of mouse liver, with an IC50 of 14 microM. GSH peroxidase I (EC 1.11.1.9) and GSH peroxidase II activities were resolved by chromatography of liver and testis cytosols. While inhibiting GSH peroxidase II with IC50 of 9-10 microM, dicumarol did not affect the activity of the selenoenzyme, GSH peroxidase I. Whereas several other non-substrate ligands were more potent inhibitors of 1-chloro-2,4-dinitrobenzene conjugation, dicumarol effectively inhibited GSH transferase and GSH peroxidase II activities in the range of dicumarol concentrations frequently used for detection of DT diaphorase action. These results indicate that physiological consequences resulting from the use of supramicromolar concentrations of dicumarol should not be interpreted in terms of DT diaphorase inhibition alone.
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PMID:Inhibition of mouse glutathione transferases and glutathione peroxidase II by dicumarol and other ligands. 138 26


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