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)

The spontaneous autoxidation of the neurotoxin 6-hydroxydopamine proceeds by a free radical chain reaction involving the superoxide anion radical and produces the corresponding chromogen 6-hydroxydopamine quinone and hydrogen peroxide. The rate of this reaction is increased in the presence of ceruloplasmin and peroxidase, and reduced by superoxide dismutase, catalase, and DT-diaphorase. We report some explanations of why these proteins may increase or reduce the rate of autoxidation of 6-hydroxydopamine.
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PMID:Modulation of 6-hydroxydopamine oxidation by various proteins. 917 10

Nitrergic and peptidergic innervation of the chick thymus was studied using histochemical and immunohistochemical methods. Nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry and anti-nitric oxide synthase (NOS) antibodies stained both nerve fibres and 'neuron-like' cells located in the septal connective tissue. NADPH-d and NOS were partially colocalised. Staining of NADPH-d positive neuron-like cells with the neuronal marker, neuron specific enolase, confirmed the neuronal nature of these cells. Antibodies against vasoactive intestinal peptide (VIP), neuropeptide tyrosine (NPY), substance P (SP) and calcitonin gene related peptide (CGRP) were used to map the peptidergic innervation of the chick thymus. The distribution of nerve fibres staining for the various neuroactive chemicals in specific thymic compartments was non-uniform. Out of all the peptides, VIP-containing nerves appeared to be the most abundant. In addition, double-labeling of the thymic sections revealed that VIP and NADPH-d were colocalised in the neuronal structures. Immunostaining of the chick embryos demonstrated that VIP, NPY, SP and CGRP were first expressed in the chick thymus during late ontogeny. The significance of these novel findings was discussed.
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PMID:Nitrergic, peptidergic and substance P innervation of the chick thymus. 947 19

Premarin (Wyeth-Ayerst) is the estrogen replacement treatment of choice and continues to be one of the most widely dispensed prescriptions in North America. In addition to endogenous estrogens, Premarin contains unsaturated equine estrogens, including equilenin [1,3,5(10),6,8-estrapentaen-3-ol-17-one]. In previous work, we showed that the equilenin metabolite 4-hydroxyequilenin (4-OHEN) can be autoxidized to 4-OHEN-o-quinone which readily entered into a redox couple with the semiquinone radical catalyzed by NAD(P)H, P450 reductase, or quinone reductase, resulting in generation of reactive oxygen species [Shen, L., Pisha, E., Huang, Z., Pezzuto, J. M., Krol, E., Alam, Z., van Breemen, R. B., and Bolton, J. L. (1997) Carcinogenesis 18, 1093-1101]. As oxidative damage to DNA by reactive oxygen species generated by redox active compounds has been proposed to lead to tumor formation, we investigated whether 4-OHEN could cause DNA damage. We treated lambda phage DNA with 4-OHEN and found that extensive single-strand breaks could be obtained with increasing concentrations of 4-OHEN as well as increasing incubation times. If scavengers of reactive oxygen species are included in the incubations, DNA could be completely protected from 4-OHEN-mediated damage. In contrast, NADH and CuCl2 enhanced the ability of 4-OHEN to cause DNA single-strand breaks presumably due to redox cycling between 4-OHEN and the semiquinone radical generating hydrogen peroxide and ultimately copper peroxide complexes. We also confirmed that 4-OHEN could oxidize DNA bases since hydrolysis of 4-OHEN-treated calf thymus DNA and HPLC separation with electrospray MS detection revealed oxidized deoxynucleosides, including 8-oxodeoxyguanosine and 8-oxodeoxyadenosine. Our data suggest that DNA single-strand breaks and oxidation of DNA bases by 4-OHEN could contribute to the carcinogenic mechanism(s) of equine estrogens.
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PMID:The equine estrogen metabolite 4-hydroxyequilenin causes DNA single-strand breaks and oxidation of DNA bases in vitro. 976 Feb 86

Choline acetyltransferase (ChAT) as a rate-limiting enzyme in the biosynthetic pathway of acetylcholine is thought to be present in all cholinergic neurons. However, its immunoreactivity has not been successfully applied to the study of cholinergic neurons in the pancreas. In a previous study in the pancreas of newborn guinea pig we reported the colocalization of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS) with various neuropeptides as well as dopamine-beta-hydroxylase (DbetaH), the enzyme responsible for converting dopamine to noradrenaline. Whether NADPH-d is colocalized with ChAT in the pancreatic neurons is not known. Also it would be interesting to find out whether noradrenaline and acetylcholine could be colocalized in the same pancreatic neurons. In the present study, a method for triple labelling of ChAT, DbetaH and NADPH-d was used to answer the above questions. Colocalization of ChAT, DbetaH and NADPH-d was constantly demonstrated in the same neurons in the same sections. It is concluded that some of the pancreatic neurons may utilize more than one neurotransmitter such as nitric oxide (NO), acetylcholine and noradrenaline to achieve their function. The possible cotransmission of acetylcholine and noradrenaline was extremely intriguing, and its mechanism and significance needs to be further investigated.
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PMID:Colocalization of ChAT, DbetaH and NADPH-d in the pancreatic neurons of the newborn guinea pig. 979 38

Induction of phase 2 enzymes (e.g., glutathione transferases, NAD(P)H:quinone reductase, glucuronosyltransferases, epoxide hydrolase) is a major strategy for reducing the susceptibility of animal cells to neoplasia and other forms of electrophile toxicity. In a search for new chemoprotective enzyme inducers, a structure-activity analysis was carried out on two types of naturally occurring and synthetic substituted phenylpropenoids: (a) Ar-CH=CH-CO-R, where R is OH, OCH3, CH3, or Ar, including cinnamic, coumaric, ferulic, and sinapic acid derivatives, their ketone analogues, and chalcones; and (b) bis(benzylidene)cycloalkanones, Ar-CH=C(CH2)n(CO)C=CH-Ar, where n = 5, 6, or 7. The potencies of these compounds in inducing NAD(P)H:quinone reductase activity in murine hepatoma cells paralleled their Michael reaction acceptor activity (Talalay, P.; De Long, M. J.; Prochaska, H. J. Proc. Natl. Acad. Sci. U.S.A. 85, 1988, 8261-8265). Unexpectedly, the bis(benzylidene)cycloalkanones also powerfully quenched the lucigenin-derived chemiluminescence evoked by superoxide radicals. Introduction of o-hydroxyl groups on the aromatic rings of these phenylpropenoids dramatically enhanced their potencies not only as inducers for quinone reductase but also as quenchers of superoxide. These potentiating o-hydroxyl groups are hydrogen-bonded, as shown by moderate downfield shift of their proton NMR resonances and their sensitivities to the solvent environment. The finding that the potencies of a series of bis(benzylidene)cycloalkanones in inducing quinone reductase appear to be correlated with their ability to quench superoxide radicals suggests that the regulation of phase 2 enzymes may involve both Michael reaction reactivity and radical quenching mechanisms.
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PMID:Chemoprotective properties of phenylpropenoids, bis(benzylidene)cycloalkanones, and related Michael reaction acceptors: correlation of potencies as phase 2 enzyme inducers and radical scavengers. 985 96

The present investigation demonstrates distinct patterns of activation for antioxidant/electrophile-responsive elements (ARE/EpREs) in cells of neuronal versus hepatic origin suggesting the possibility of cell-/tissue-specific signaling pathways and/or transcription factors required for ARE/EpRE activation. The ARE/EpRE is a cis-acting regulatory element found in 5'-flanking regions of numerous genes including NAD(P)H:quinone oxidoreductase (QR) and glutathione S-transferases. Insomuch as ARE/EpRE activation has been studied primarily in hepatoma cell lines there is little information on how these responsive elements and corresponding genes are regulated in brain. ARE/EpRE-reporter constructs were transiently transfected into IMR-32 human neuroblastoma cells. Activation of ARE/EpRE sequences by tert-butylhydroquinone (tBHQ), a redox-cycling compound, in IMR-32 cells (20- to 30-fold) is dramatically different from the minimal response seen in HepG2 human hepatoma cells (2- to 3-fold). beta-napthoflavone, an ARE/EpRE inducer in HepG2 cells, as well as the oxidants hydrogen peroxide and tert-butyl hydroperoxide did not induce the ARE/EpRE in IMR-32 cells. In addition, we show that the core sequence containing a complete 5' palindrome is necessary for maximal activation of the ARE/EpRE in IMR-32 cells. Mutations within this palindromic sequence decrease basal level expression and block induction by tBHQ but not phorbol 12-myristate 13-acetate. Furthermore, activation of the hQR-ARE/EpRE by tBHQ correlates with induction of endogenous QR activity in IMR-32 neuroblastoma cells (15-fold). Thus, elucidating the mechanism of ARE/EpRE activation in this human neuroblastoma cell line may identify unknown transcription factors or signal transduction cascades regulating ARE/EpRE-driven gene expression.
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PMID:Activation of antioxidant/electrophile-responsive elements in IMR-32 human neuroblastoma cells. 1004 3

Neutral red (NR) functioned as an electronophore or electron channel enabling either cells or membranes purified from Actinobacillus succinogenes to drive electron transfer and proton translocation by coupling fumarate reduction to succinate production. Electrically reduced NR, unlike methyl or benzyl viologen, bound to cell membranes, was not toxic, and chemically reduced NAD. The cell membrane of A. succinogenes contained high levels of benzyl viologen-linked hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U) activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not. Proton translocation by whole cells was dependent on either electrically reduced NR or H2 as the electron donor and on the fumarate concentration. During the growth of Actinobacillus on glucose plus electrically reduced NR in an electrochemical bioreactor system versus on glucose alone, electrically reduced NR enhanced glucose consumption, growth, and succinate production by about 20% while it decreased acetate production by about 50%. The rate of fumarate reduction to succinate by purified membranes was twofold higher with electrically reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)-4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited succinate production from H2 plus fumarate but not from electrically reduced NR plus fumarate. Thus, NR appears to replace the function of menaquinone in the fumarate reductase complex, and it enables A. succinogenes to utilize electricity as a significant source of metabolic reducing power.
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PMID:Utilization of electrically reduced neutral red by Actinobacillus succinogenes: physiological function of neutral red in membrane-driven fumarate reduction and energy conservation. 1019 2

Dopaminochrome formation is catalyzed by commercially available purified peroxidases (EC 1.11.1.7) such as horseradish, lacto- and myelo-peroxidase using dopamine, hydrogen peroxide or promethazine sulfoxide as substrates. A rat brain fraction (RBF) catalyzes a similar reaction and its catalytic power increases after preincubation with hydrogen peroxide/ascorbic acid. The activity of both the purified enzymes and the RBF preparation is inhibited by carnosine and characterized by excess substrate inhibition. The enzymes recognize different substrates but show the highest affinity for dopamine. The RBF fraction is strongly buffered against oxidation by compounds such as glutathione and by bioreductive enzymes such as DT-diaphorase (EC 1.6.99.2) which can use as a substrate menadione or dopaminochrome. The rat brain dopamine peroxidizing activity appeared to be mostly bound to the synaptosomal fraction. The reaction catalyzed by the purified peroxidases was followed by electron spin resonance spectroscopy and, unlike that catalyzed by RBF, was shown to produce the signal of a transient dopamine-o-semiquinone radical.
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PMID:A rat brain fraction and different purified peroxidases catalyzing the formation of dopaminochrome from dopamine. 1035 Jun 48

2-Amino-3-carboxy-1,4-naphthoquinone (ACNQ) is a novel growth stimulator for bifidobacteria. The role of ACNQ as a mediator of the electron transfer from NAD(P)H to dioxygen (O(2)) and hydrogen peroxide (H(2)O(2)), proposed in our previous paper, was examined using the cell-free extract and whole cells of Bifidobacterium longum. Continuous monitoring of ACNQ, O(2) and H(2)O(2) by several amperometric techniques has revealed that ACNQ works as a good electron acceptor of NAD(P)H diaphorase and that the reduced form of ACNQ is easily autoxidized and also acts as a better electron donor of NAD(P)H peroxidase than NAD(P)H. The generation of H(2)O(2) by B. longum under aerobic conditions is effectively suppressed in the presence of ACNQ. These ACNQ-mediated reactions would play roles as NAD(P)(+)-regeneration processes. The accumulation of ACNQ in the cytosol has been also suggested. These characteristics of ACNQ seem to be responsible for the growth stimulation of bifidobacteria. Vitamin K(3), which has an extremely low growth-stimulating activity and was used as a reference compound, exhibits much lower activity as an electron transfer mediator. The difference in the activity is discussed in terms of the redox potential and partition property of the quinones.
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PMID:Role of 2-amino-3-carboxy-1,4-naphthoquinone, a strong growth stimulator for bifidobacteria, as an electron transfer mediator for NAD(P)(+) regeneration in Bifidobacterium longum. 1043 42

The pyrrolo[1,2-a]benzimidazole (PBI) reductive alkylating agents have been investigated in this laboratory since their discovery in the late 1980s. Of all the structural modifications of the PBIs investigated so far, the variation of the 3-substituent has the greatest influence on cytotoxicity, toxicity, and in vivo antitumor activity. In the present study, we prepared both the R and S enantiomers of nitrogen-containing 3-substituents possessing hydrogen-bonding capability as well as varying basicity. The rationale was to take advantage of stereoselective DT-diaphorase reductive activation as well as hydrogen bonding in the DNA major groove. As a result of these studies, analogues were discovered possessing among the highest hollow fiber tumor assay scores observed in hundreds of natural and synthetic antitumor agents. Our findings indicate that a relatively basic 3-substituent is required for outstanding PBI cytotoxicity but that the importance of using pure enantiomers is still open to study.
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PMID:Design of highly active analogues of the pyrrolo[1,2-a]benzimidazole antitumor agents. 1046 19


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