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)

This study demonstrates the menadione-dependent reduction of imipramine N-oxide, a tertiary amine N-oxide, to imipramine by rat liver cytosol in the presence of NADH or NADPH. A mechanism for the cytosolic reduction of the tertiary amine N-oxide is proposed. Menadione is converted to its reduced form by a menadione-reducing enzyme such as DT-diaphorase and the reduced pyridine nucleotide, followed by reduction of the tertiary amine N-oxide to the amine by the heme group of catalytic hemoproteins in the presence of reduced menadione as an electron donor.
Biochem Mol Biol Int 1997 Jun
PMID:Menadione-dependent reduction of tertiary amine N-oxide by rat liver cytosol. 923 25

We have synthesized nitroaromatic derivatives of triterpenoid betulin (lup-20(29)-ene-3 beta, 28-diol), betulin-(28)-5'-(aziridin-1-yl)-2',4'-dinitrobenzoate and betulin-(28)-5'-nitro-2'-furoate. These compounds were reduced in single-electron way by ferredoxin: NADP+ reductase and flavocytochrome b2 at rates comparable with their simple structure analogs. Besides, these compounds were substrates for DT-diaphorase. Their toxicity to bovine leukemia virus-transformed lamb fibroblast culture was partly prevented by antioxidant N,N'-diphenyl-p-phenylene diamine and desferrioxamine, indicating an involvement of oxidative stress in their cytotoxicity.
Biochem Mol Biol Int 1997 Jun
PMID:Nitroaromatic betulin derivatives as redox cycling agents. 923 38

The experiments reported here were undertaken to test the hypothesis that the antioxidative, reduced form of hydrophobic phase coenzyme Q (CoQ) may be generated and maintained by the two-electron quinone reductase, DT-diaphorase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] by catalyzing formation of the hydroquinone form of CoQ. This enzyme was isolated and purified from rat liver cytosol and its reduction of several CoQ homologs incorporated into large unilamellar vesicles (LUVETs) was demonstrated. The addition of NADH and DT-diaphorase to LUVETs and to multilamellar vesicles (MLVs) containing CoQ homologs, including CoQ9 and CoQ10, resulted in essentially complete reduction of the CoQ. Incorporation of either CoQ9H2 or CoQ10H2 and the lipophylic radical generator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) into MLVs in the presence of DT-diaphorase and NADH maintained the reduced state of CoQ and inhibited lipid peroxidation. The reaction between DT-diaphorase and CoQ was also demonstrated in isolated rat liver hepatocytes in which incorporation of CoQ10 provided protection from adriamycin (adr)-induced mitochondrial membrane damage. The role of DT-diaphorase in the antioxidant activity of CoQ was demonstrated by the co-incorporation of dicoumarol (dic), a potent inhibitor of DT-diaphorase, resulting in a loss of protection by incorporated CoQ10. These results support the antioxidant function of DT-diaphorase in both artificial and natural membrane systems by acting as a two-electron CoQ reductase which forms and maintains CoQ in the reduced state.
Mol Aspects Med 1997
PMID:The two-electron quinone reductase DT-diaphorase generates and maintains the antioxidant (reduced) form of coenzyme Q in membranes. 926 2

alpha-Tocopherolquinone (TQ), a product of alpha-tocopherol oxidation, can function as an antioxidant after reduction to alpha-tocopherolhydroquinone (TQH2). We examined the ability of human NAD(P)H:quinone oxidoreductase (NQO1) to catalyze the reduction of TQ to TQH2 in cell-free and cellular systems. In reactions with purified human NQO1, TQ was reduced to TQH2. Kinetic parameters for the reduction of TQ by NQO1 (Km = 370 microM; k(cat) = 5.6 x 10(3) min(-1); k(cat)/Km = 15 min(-1) x microM(-1)) indicate that NQO1 can efficiently reduce TQ to TQH2. A comparison of the rate of reduction of TQ and coenzyme Q10 by NQO1 showed that TQ is reduced more efficiently than coenzyme Q10. Experiments with either Chinese hamster ovary (CHO) cells stably transfected with human NQO1 or CHO cell sonicates demonstrated a correlation between NQO1 activity and TQ reduction to TQH2. CHO cells with elevated NQO1 generated and maintained higher levels of TQH2 after treatment with TQ relative to NQO1-deficient CHO cells. TQH2 generated from NQO1-mediated reduction of TQ prevented cumene hydroperoxide-induced lipid peroxidation in rat liver microsomes. In addition, cumene hydroperoxide-induced lipid peroxidation was inhibited more efficiently by TQ in CHO cell lines with elevated NQO1 activity. These data demonstrate that NQO1 can reduce TQ to TQH2 and that TQH2 can function as an efficient antioxidant. This work suggests that one of the physiological functions of NQO1 may be to regenerate antioxidant forms of alpha-tocopherol.
Mol Pharmacol 1997 Aug
PMID:The reduction of alpha-tocopherolquinone by human NAD(P)H: quinone oxidoreductase: the role of alpha-tocopherolhydroquinone as a cellular antioxidant. 927 53

Quinone reductases in sea bream, Pagrus major, were investigated using menadione as a model quinone. Both NADPH-linked and NADH-linked quinone reductase activities were detected, in varying degrees, in all tissues examined. In the liver, these activities resided in its microsomal and cytosolic fractions. The cytosolic activity was markedly inhibited by cupric sulfate and p-chloromercuribenzoate. However, little effect was observed with dicoumarol, a potent inhibitor of DT-diaphorase. The NADH-linked activity was more resistant to heat inactivation than the NADPH-linked activity. The NADPH-linked quinone reductase was purified from the liver cytosol by chromatography with DEAE-cellulose, hydroxyapatite and AF-Blue Toyopearl. The molecular weight of the enzyme was estimated to be 68,000 by gel filtration and 32,000 by SDS-PAGE. The NADH-linked quinone reductase was purified from the liver cytosol by heat treatment, fractionation with ammonium sulfate and chromatography with phenyl-Toyopearl, hydroxyapatite, DEAE-cellulose and hydroxyapatite. The molecular weight of the enzyme was estimated to be 124,000 by SDS-PAGE and 126,000 by gel filtration.
Comp Biochem Physiol B Biochem Mol Biol 1997 Nov
PMID:Purification of NADPH-linked and NADH-linked quinone reductases from liver cytosol of sea bream, Pagrus major. 946 79

PD98059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one] is a flavonoid and a potent inhibitor of mitogen-activated protein kinase kinase (MEK). Concentrations of PD98059 of </=20 muM were not cytotoxic to cultures of the immortalized human breast epithelial cell line MCF10A. The agent was weakly cytostatic at concentrations of >/=10 microM. In vivo exposure of cultures to </=20 microM PD98059 for 2-22 hr did not affect overall extracellular signal-regulated kinase contents; however, exposure to PD98059 resulted in a rapid loss (>95%) of the dually phosphorylated forms of extracellular signal-regulated kinase (IC50 = 1 muM). Treatment of cultures with PD98059 of >/=1 muM either at the time of addition or up to 48 hr before the addition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed in a concentration-dependent manner the accumulation of induced steady state CYP1A1, CYP1B1, and NQO1 mRNAs. The addition of PD98059 to rat liver cytosol just before the addition of TCDD suppressed TCDD binding (IC50 = 4 muM) and aryl hydrocarbon receptor (AHR) transformation (IC50 = 1 muM), as measured by sucrose gradient centrifugation and electrophoretic mobility shift assays. Flavone and flavanone, two closely related structural analogs of PD98059, inhibited AHR transformation by TCDD with IC50 values similar to that obtained with PD98059. However, neither analog was as potent as PD98059 in inhibiting MEK (IC50 approximately 190 muM for both). These results suggest that PD98059 is a ligand for the AHR and functions as an AHR antagonist at concentrations commonly used to inhibit MEK and signaling processes that entail MEK activation.
Mol Pharmacol 1998 Mar
PMID:PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase. 949 9

Differentiation from replicating slender forms to non-dividing stumpy bloodstream forms of T. brucei limits the parasite population size in the mammalian host in addition to and independently of the antibody response. Using a culture system for pleomorphic strains of T. brucei we show that slender forms very efficiently differentiate to stumpy forms in vitro and that the induction of differentiation is correlated to cell density. Differentiation in the host and in culture were compared using a battery of markers including cell morphology and volume, cell cycle position, the kinetics of the differentiation, expression of NADH dehydrogenase (diaphorase), expression of several differentially regulated transcripts and the kinetics of transformation to replicating procyclic forms after induction with cis-aconitate. By all available criteria, differentiation in culture reflects the natural process in the mammalian host. Time course experiments reveal a very tight temporal correlation between cell cycle arrest of bloodstream forms, appearance of a stumpy differentiation marker and the competence of a bloodstream form population to initiate transformation to procyclic forms in response to cis-aconitate. Our results show that induction of bloodstream form differentiation can occur independently of host-derived cues. We suggest a density sensing mechanism which induces differentiation to the non-dividing stumpy stage and thereby enables the parasite population to autoregulate its proliferation.
Mol Biochem Parasitol 1997 Dec 01
PMID:Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture. 949 48

The extracellular menadione-catalyzed H2O2 production by NIH/3T3 cells was expected to depend on plasma membrane-bound NAD(P)H:quinone oxidoreductase. This enzyme was estimated to be a flavoprotein with the molecular mass of 70 KDa. Km values of plasma membrane-bound NAD(P)H:quinone oxidoreductase producing H2O2 were 60 microM for NADH and 150 microM for NADPH. Ca2+ ionophore A23187 controlled menadione-catalyzed H2O2 production by the cells in time- and concentration-dependent manner.
Biochem Mol Biol Int 1998 Mar
PMID:Characterization of extracellular menadion-catalyzed H2O2 production by NIH/3T3 cells. 955 17

The carotid body plays an important role in ventilatory adaptation during chronic hypoxia. Nitric oxide (NO) may act as a regulator in neurotransmission, influencing the carotid body chemosensory discharge. The aim of the study was to understand if NO could contribute to the adaptation process during chronic hypoxia. The rats were kept in chronic hypoxia (10-11% inspired oxygen) for 12 days, while the controls were kept in room air (21% O2). The distribution for diaphorase activity and immunohistochemistry for nitric oxide synthase (NOS) showed that chronic hypoxia induces an increase in NOS activity in the carotid body. It was concluded that NO release increased during chronic hypoxia and causes an inhibitory effect on carotid chemosensory discharge of the rat carotid body.
Comp Biochem Physiol A Mol Integr Physiol 1998 Jun
PMID:Does chronic hypoxia increase rat carotid body nitric oxide? 977 3

Several studies, including histochemical ones, have indicated that nitric oxide (NO) of endothelial origin may be related to the pulmonary vasodilation that occurs at birth. Since no histologic studies have been done of the possible parallel perinatal increase in production of neuronal NO synthase (nNOS) by pulmonary nerve plexuses, we investigated the distribution of nNOS in fetal, neonatal, and adult mouse lung. Lungs from mice aged 13 d gestation to 6 d after birth and lungs of adults were studied through histochemistry for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and immunocytochemistry. Both techniques gave almost similar results in relation to time of appearance, distribution, and frequency of neural structures positive for NADPH-d and NOS. NADPH-d staining was also applied to whole mounts of developing and adult tracheae. Staining was found from gestational days 13 to 15 onward in a small portion of the neuronal population. In all stages studied, NADPH-d/NOS staining was found in neuron cell bodies in the hilar region and bronchiolar wall, as well as in neuronal processes. Labeled terminal nerve fibers with varicosities were more frequent in pulmonary blood vessels than in airways. In tracheae, similar NADPH-d/NOS-positive nerve plexuses were found. The presence of nNOS in fetal and neonatal mouse respiratory tract suggests that neurally derived NO must play a role in developing lung physiology. However, because no perinatal increase in the number or intensity of staining of nNOS-positive nerve structures was seen, no apparent relation between neural NO and vasodilation can be established at birth.
Am J Respir Cell Mol Biol 1999 Feb
PMID:Histochemical demonstration of neuronal nitric oxide synthase during development of mouse respiratory tract. 992 27


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