Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.8.1.4 (diaphorase)
 2,754 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies concern the initial steps in 4-nitroquinoline 1-oxide (4NQO) metabolism in relation to mechanisms of anticarcinogenesis. Butylated hydroxyanisole (BHA) administration by a protocol known to inhibit the pulmonary tumorigenicity of 4NQO in A/HeJ mice enhanced hepatic and pulmonary activities for 4NQO metabolism by two major pathways, conjugative detoxification and nitroreductive activation. High-performance liquid chromatography analysis showed approximate doubling of two types of glutathione transferase subunits with 4NQO-conjugating activity in livers of BHA-treated mice. Similar increases were observed in hepatic 4NQO-conjugating activity and in Vmax, while Km for 4NQO was 39 to 43 microM. Pulmonary 4NQO-glutathione transferase activity increased 24 to 29%. DT diaphorase activity toward 4NQO was elevated 3.3-fold in livers and 2.7-fold in lungs of BHA-treated mice. However, the predominant 4NQO reductase of liver and lung was dicumarol resistant, had a strong preference for NADH, and showed little if any response to BHA. This Mr 200,000 enzyme, partially purified from livers of Swiss mice, exhibited the stoichiometry of 2-NADH/4NQO expected for reduction of 4NQO to 4-hydroxyaminoquinoline 1-oxide. Its high affinity for 4NQO (Km, 15 microM) signified a much greater influence on 4NQO metabolism than DT diaphorase (Km, 208 microM). The dicumarol-resistant 4NQO reductase differed from several known cytosolic nitroreductases. The results suggest that protection by BHA may result from alteration of the balance between 4NQO activation and conjugation.
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PMID:Nitroreductases and glutathione transferases that act on 4-nitroquinoline 1-oxide and their differential induction by butylated hydroxyanisole in mice. 137 76

The c14CoS/c14CoS mouse has a homozygous deletion of about 1.2 cM on chromosome 7 that includes the albino (c) locus. The untreated 14CoS/14CoS newborn has been reported to exhibit a marked transcriptional activation of the hepatic NAD(P)H:menadione oxidoreductase (Nmo-1; DT diaphorase; quinone reductase; azo dye reductase) gene, as well as elevated UDP glucuronosyl-transferase (UGT1*06) and glutathione transferase (GT1) activities, when compared with the cch/cch wild-type and the cch/c14CoS heterozygote. We show here that the newborn hepatic activities of seven enzymes that play a role in the oxidative stress response--NMO1, UGT1*06, GT1, copper-zinc superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase--are increased 1.5- to 25-fold in 14CoS/14CoS, as compared with ch/ch and ch/14CoS mice. The activities of four additional enzymes having no known association with the oxidative stress response--benzo[a]pyrene hydroxylase (CYP1A1, cytochrome P(1)450), acetanilide 4-hydroxylase (CYP1A2, cytochrome P(3)450), lactate dehydrogenase (LDH), and NADPH-cytochrome c reductase--are not significantly different among the three genotypes. These data suggest that there exists an "oxidative stress" response in the untreated 14CoS/14CoS newborn. We postulate that a chromosome 7 regulatory gene, which we have named Nmo-1n, might encode a trans-acting negative effector of the Nmo-1 gene, and genes corresponding to the other elevated enzymic activities described above. When both copies of Nmo-1n are deleted, as is the case in 14CoS/14CoS mice, a battery of genes involved in oxidative stress is released from negative control and becomes activated--despite the absence of any apparent oxidative insult by foreign chemicals.
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PMID:"Oxidative stress" response in liver of an untreated newborn mouse having a 1.2-centimorgan deletion on chromosome 7. 154 Jan 61

o-Quinones are easily formed by oxidation of physiologically relevant catechols. These reactions mainly occur in two specialized cells, catecholaminergic neurons and melanocytes. Both types of cells are related ontogenetically, as they arise from the neural crest during the developmental differentiation. o-Quinones are used to form melanin, a protective pigment formed by different mechanisms in melanocytes and catecholaminergic neurons. However, the reactivity of these quinones makes their presence in the cytosol dangerous for the cell survival and these compounds have been proposed as degenerative and apoptotic agents. Thus, melanin-producing cells show several potential mechanisms to protect themselves against the noxious effects of o-quinones. In melanocytes, the most effective autoprotecting mechanisms are the existence of malanosomes as a confined site for melano-synthesis and the action of tyrosinase-related protein 2 (TRP2) to drive L-dopachrome to 5,6-dihydroxyindole-2-carboxylic acid minimizing the formation of 5,6-dihydroxyindole. In catecholaminergic neurons, recent data suggest that glutathione transferase (GST M2-2 isoenzyme) and macrophage migration inhibitory factor (MIF) are very effective in preventing long-lived formation of dopaminechrome and noradrenochrome, although the detoxification reactions are different (conjugation to GSH or isomerization respectively). These mechanisms are less efficient for adrenochrome, although MIF and GST M1-1 could also catalyze similar reactions using this compound as substrate. In addition, the formation of adrenochrome is still under discussion, and adrenolutin formation could contribute to deactivate its harmful effects. The contribution of D-dopachrome tautomerase to these mechanisms is yet unknown, although in contrast to MIF, that enzyme does not recognize catecholaminechromes as substrates. Diaphorase could also be protective against quinones, since this enzyme catalyzes their bielectronic reduction back to catechols, thus preventing the formation of chrome species. This activity has been described in melanocytes and neurons, so that its contribution should be further investigated. In contrast to diaphorase, cytochrome P450 reductase should not be considered a protective enzyme, since its monoelectronic reduction of quinones leads to formation of semiquinones, that is, even more noxious than the quinones.
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PMID:Neurotoxicity due to o-quinones: neuromelanin formation and possible mechanisms for o-quinone detoxification. 1283 99

Lactobacillus is a probiotic commonly used for supplementation to human and animal diets. In this study, we used 2-DE and MS to analyze changes in the proteomes of Lactobacillus and intestinal epithelial cells in two model systems. The in vivo and in vitro models were involved the inoculation of Lactobacillus fermentum I5007 into the rabbit jejunum for 4 h and the culture of the bacterium with Caco-2 cells for 1 h, respectively. Our results indicate that, after exposure to the intestinal environment, the bacterium exhibited decreases in key enzymes involved in energy metabolism (e.g., lactate dehydrogenase, dihydrolipoamide dehydrogenase, and nicotinate phosphoribosyltransferase) and amino acid metabolism (e.g., arginyl-tRNA synthetase and aspartate-semialdehyde dehydrogenase), but increases in glycoside hydrolase (an enzyme for mucin degradation) and fructose-6-phosphate phosphoketolase (an enzyme of the pentose phosphate pathway). In response to an interaction with L. fermentum I5007, Caco-2 cells showed changes in proteins that were beneficial for gut integrity, including voltage-dependent anion channel 1, glutathione transferase, and heat shock protein gp96. On the basis of their functions, we suggest that these proteins serve as useful biomarkers for metabolic changes in Lactobacillus and intestinal epithelial cells in response to their interactions.
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PMID:2-DE and MS analysis of interactions between Lactobacillus fermentum I5007 and intestinal epithelial cells. 1800 11