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 metabolic activation of a variety of quinone-based anticancer agents occurs, in part, as a result of the bioreductive activation by the flavoprotein NAD(P)H:quinone-acceptor oxidoreductase (NQO1) (EC 1.6.99.2). Using the COMPARE algorithm (http://dtp.nci.nih.gov), a significant statistical correlation has been found in the NCI in vitro anticancer drug screen between high endogenous expression of the pro-apoptotic protein BAD, NQO1 enzymatic activity, and the cytotoxicity of certain antitumor quinones. Two statistically correlated groups of quinones can be discerned: positive-correlated compounds, which are more active in cell lines expressing high baseline levels of BAD protein and NQO1 activity (e.g. the MCF-7 breast carcinoma), and negative-correlated compounds, which are more active in cell lines with undetectable levels of BAD and NQO1 activity (e.g. the HL-60 myeloid leukemia). In the present study, the relationship between quinone structure, redox cycling, and cytotoxicity in the MCF-7 and HL-60 cell lines was investigated. A good biological correlation exists between cytotoxicity and NQO1 activity, BAD protein levels and apoptosis, but not always between cytotoxicity and intracellular reactive oxygen species levels. The overall markedly increased cytotoxicity of the aziridinylbenzoquinone compounds used in this study is accompanied by apoptosis, which occurs mostly through a cytochrome c-independent pathway.
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PMID:Cytotoxicity and apoptosis of benzoquinones: redox cycling, cytochrome c release, and BAD protein expression. 1266 42

Malic dehydrogenase activity of the kidney homogenate from the normal and the tuberculous guinea pigs has been estimated. A defect in the electron transport chain has been detected at the level of flavoprotein-diaphorase system. A significantly high DPNase activity of kidney homogenate has also been found in the infected group. Niacin and phenazine methochloride could correct both the defects and improve the tetrazolium reduction of the homogenate in the infected group to the level of the normal activity. Oxidative phosphorylation by the kidney mitochondria from the tuberculous guinea pigs was found to be low and could not be improved by niacin and phenazine methochloride, unlike their effects on the reduction of tetrazolium. Results have been discussed in the light of the over-all intercellular economy and its relation to the symptom complexes in tuberculosis.
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PMID:Metabolism in infection: study on the enzymatic damage in kidney of guinea pig infected with Mycobacterium tuberculosis. 1402 Apr

Dworkin, Martin (University of Minnesota, Minneapolis), and Donald J. Niederpruem. Electron transport system in vegetative cells and microcysts of Myxococcus xanthus. J. Bacteriol. 87:316-322. 1964.-Respiration by intact cells of the fruiting myxobacterium Myxococcus xanthus is cyanide-sensitive and can be demonstrated in the vegetative cells but not in the microcysts. Cell-free particles from both vegetative cells and microcysts have cyanide-sensitive reduced nicotinamide adenine dinucleotide (NADH) oxidase, diaphorase, NADH cytochrome c reductase, and cytochrome oxidase activities. While the vegetative cell specific activities for NADH oxidase and diaphorase are slightly higher than those for the microcysts, the microcysts have ten times the cytochrome c reductase and cytochrome oxidase activities of the vegetative cells. Furthermore, the respiration of the microcyst particles is considerably less cyanide-sensitive than is that of the vegetative-cell particles. Difference spectra of the cell-free particles of vegetative cells and microcysts are qualitatively identical, showing the presence of b- and c-type cytochrome and flavoprotein. The a-type pigments are clearly present in the extracts of the vegetative cells and are suggested by the spectrum of the microcyst particles. The cytochrome oxidase activity of both extracts is consistent with the presence of a-type pigments in both. The spectra of the carbon monoxide-binding pigments were determined and, by this parameter, qualitative differences appear between the vegetative cells and the microcysts.
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PMID:ELECTRON TRANSPORT SYSTEM IN VEGETATIVE CELLS AND MICROCYSTS OF MYXOCOCCUS XANTHUS. 1415 Oct 50

Downey, Ronald J. (University of Notre Dame, Notre Dame, Ind.). Vitamin K-mediated electron transfer in Bacillus subtilis. J. Bacteriol. 88:904-911. 1964.-Electron transfer enzymes were obtained from log-phase cells of Bacillus subtilis after aerobic and anaerobic cultivation. The cytochrome content was found to be related to oxygen tension, there being little, if any, cytochrome operative in anaerobic cells. Vitamin K levels in the two cell types did not vary as markedly. A soluble diaphorase-type flavoprotein was obtained from both types of cells which reacted with vitamin K(2), K(3), and certain dyes but not bovine cytochrome c. Almost 90% of this diaphorase activity was leached from intact protoplasts without the use of solvating agents or sonic oscillation. Electron transport particles capable of coupled phosphorylation were inhibited by light (360 mmu) or 2,3-dimercaptopropanol (BAL), whereas these had no effect on the diaphorase activity. Phosphorylation in a BAL-inhibited system was restored after addition of the soluble diaphorase from either aerobic or anaerobic cells. The results suggested that soluble flavoprotein components are linked to vitamin K in both fermentative and phosphorylative pathways, and that this segment is indispensable to aerobic and anaerobic respiration in the bacillus.
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PMID:VITAMIN K-MEDIATED ELECTRON TRANSFER IN BACILLUS SUBTILIS. 1421 53

The purpose of our study was to determine the effect of dilution and liquid-preservation of boar sperm on oxidoreductive capability of their mitochondria. The semen was diluted with BTS extender produced from water purified by destillation or by reverse osmosis. The spermatozoa were stored over a four-day period at 16-18 degrees C. The function of sperm mitochondria was assessed using the screening cytochemical test for NADH-dependent oxidoreductases (diaphorase/NADH, related to flavoprotein). Morphological assessment of cytochemical reaction was carried out using a light microscope. The intensity of the reaction was evaluated by means of a computer image analysing system (Quantimet 600S), measuring the integrated optical density (IOD) and mean optical density (MOD) of the reaction product (formazans) occurring in the sperm midpieces. In the non-diluted semen, intensive cytochemical reaction throughout the length of the sperm midpiece was observed. Furthermore, spermatozoa with the intensive reaction displayed the high optical density values. After dilution the semen with two variants of experimental extender, and as the conservation time expired, the cytochemical reaction was less intensive. Moreover, the absence of formazan deposits in various parts of the sperm midpiece was also noted. These morphological features corresponded to low values of optical density. These findings suggest that the dilution of semen and the time of sperm preservation may be critical factors that handicap energy metabolism of sperm mitochondria. The type of water used in preparing BTS extender does not have any significant effect on the oxidoreductive capability of sperm boar mitochondria.
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PMID:Oxidoreductive capability of boar sperm mitochondria in fresh semen and during their preservation in BTS extender. 1466 39

Oxidative stress resistance is one of the key properties that enable pathogenic bacteria to survive the toxic reactive oxygen species released by the host. In a previous study characterizing oxidative stress resistance mutants of Helicobacter pylori, a novel potential antioxidant protein (MdaB) was identified by the observation that the expression of this protein was significantly upregulated to compensate for the loss of other major antioxidant components. In this study, we characterized an H. pylori mdaB mutant and the MdaB protein. While the wild-type strain can tolerate 10% oxygen for growth, the growth of the mdaB mutant was significantly inhibited by this oxygen condition. The mdaB mutant is also more sensitive to H(2)O(2), organic hydroperoxides, and the superoxide-generating agent paraquat. Although the wild-type strain can survive more than 10 h of air exposure, exposure of the mutant strain to air for 8 h resulted in recovery of no viable cells. The oxidative stress sensitivity of the mdaB mutant resulted in a deficiency in the ability to colonize mouse stomachs. H. pylori was recovered from 10 of 11 mouse stomachs inoculated with the wild-type strain, with about 5,000 to 45,000 CFU/g of stomach. However, only 3 of 12 mice that were inoculated with the mdaB mutant strain were found to harbor any H. pylori, and these 3 contained less than 2,000 CFU/g of stomach. A His-tagged MdaB protein was purified and characterized. It was shown to be a flavoprotein that catalyzes two-electron transfer from NAD(P)H to quinones. It reduces both ubiquinones and menaquinones with similar efficiencies and preferably uses NADPH as an electron donor. We propose that the physiological function of the H. pylori MdaB protein is that of an NADPH quinone reductase that plays an important role in managing oxidative stress and contributes to successful colonization of the host.
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PMID:An NADPH quinone reductase of Helicobacter pylori plays an important role in oxidative stress resistance and host colonization. 1497 43

NQO1 is a cytosolic flavoprotein that plays a dual role in the detoxification of potentially carcinogenic compounds and the bioreductive activation of quinone based anticancer drugs. Two polymorphic variants of NQO1 exist (NQO1*2 and NQO1*3) which cause significant phenotypic reductions in NQO1 protein content and activity. Current methods for detecting NQO1 polymorphisms commonly use PCR-RFLP techniques and have exclusively used DNA isolated from fresh tissues. This study describes a method that is suitable for analysing NQO1 polymorphisms in genomic DNA isolated from formalin-fixed paraffin-embedded tissue. The method utilises two rounds of PCR amplification using a nested primer strategy that generates specific PCR products followed by RFLP analysis using either Hinf1 (for NQO1*2) or Msp1 (for NQO1*3). Whilst existing methods proved unsatisfactory (low product yield and poor specificity), the nested primer strategy produced good quality PCR products suitable for RFLP analysis and genotyping of NQO1*2 and NQO1*3 in archival tissue samples. The ability to utilise the vast archives of human tissue held by pathology laboratories would be of considerable benefit as retrospective studies comparing NQO1 genotype status, patient history and treatment outcomes could be conducted.
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PMID:Detection of (NAD(P)H:Quinone oxidoreductase-1, EC 1.6.99.2) 609C-->T and 465C-->T polymorphisms in formalin-fixed, paraffin-embedded human tumour tissue using PCR-RFLP. 1501 Aug 41

Dopamine (DA) autooxidation, and consequent formation of neurotoxic DA-derived quinones and reactive oxygen species, has been implicated in dopaminergic cell death and, hence, in the pathogenesis of Parkinson's disease (PD). Stimulation of pathways involved in the detoxication of DA-quinones in the brain is hypothesized to be an effective means to limit oxidative stress and to confer neuroprotection in PD. In this respect, the inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) is of particular interest as it is directly implicated in the detoxication of DA-quinones and, in addition, has broad spectrum anti-oxidant properties. To study the potential pathophysiological role of NQO1 in PD, the cellular expression of NQO1 was examined in the mesencephalon of PD patients and age-matched controls. In the substantia nigra pars compacta (SNpc), NQO1 was found to be expressed in astroglial and endothelial cells and, albeit less frequently, also in dopaminergic neurons. Moreover, while overt NQO1 immunoreactivity was absent in the surrounding nervous tissue, in the Parkinsonian SNpc a marked increase in the astroglial and neuronal expression of NQO1 was consistently observed.
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PMID:Expression of NAD(P)H:quinone oxidoreductase in the normal and Parkinsonian substantia nigra. 1531 71

This paper is a brief overview of current knowledge about DT-diaphorase [NAD(P)H: Quinone Oxidoreductase, NQO], flavoprotein that catalyzes the obligatory two-electron reduction of a wide variety of substrates. The most efficient substrates are quinones but the enzyme will also reduce quinone-imines, nitro and azo compounds. NQO is unique among known NAD(P)H-oxidizing flavoproteins in being a 2-electron transferring quinone reductase, and play a major role in preventing one-electron reduction of exogenous quinones by other enzymes to auto-oxidable semiquinones and concomitant superoxide-radical generation. Induction of NQO by a variety of xenobiotics (potential sources of free-radical formation which lead to DNA and cell damage) provides protection from the cytotoxic and carcinogenic effects of these compounds. NQO has an important role in the bioreductive activation of various quinones used in cancer chemotherapy.
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PMID:Role of Nad(P)h: quinone oxidoreductase in the regulation of intracellular redox state. 1552 70

Diaphorase was studied as a possible oxidoreductase participating in NO production from some vasorelaxants. In the presence of NADH or NADPH, diaphorase can convert selected NO donors, glycerol trinitrate (GTN) and formaldoxime (FAL) to nitrites and nitrates with NO as an intermediate. This activity of diaphorase was inhibited by diphenyleneiodonium (DPI) (inhibitor of some NADPH-dependent flavoprotein oxidoreductases), while it remained uninhibited by NG-nitro-L-arginine methyl ester (inhibitor of NO synthase) 7-Ethoxyresorufin (inhibitor of cytochrome P-450 1A1 and cytochrome P-450 NADPH-dependent reductase) inhibited the conversion of GTN only. Existence of NO as an intermediate of the reaction was supported by results of electron paramagnetic resonance spectroscopy. In addition to its ability to affect the above mentioned NO donors, diaphorase was able to reduce 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and thus to eliminate its NO scavenging effect. This activity of diaphorase could also be inhibited by DPI. The reaction of diaphorase with GTN and PTIO was not affected by superoxide dismutase (SOD) or catalase. Reaction of FAL with diaphorase was lowered with SOD by 38 % indicating the partial participation of superoxide anion probably generated by the reaction of diaphorase with NADH or NADPH. Catalase had no effect. Diaphorase could apparently be one of the enzymes participating in the metabolism of studied NO donors to NO. The easy reduction and consequent elimination of PTIO by diaphorase could affect its use as an NO scavenger in biological tissues.
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PMID:Diaphorase can metabolize some vasorelaxants to NO and eliminate NO scavenging effect of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). 1558 29


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