Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An expressed sequence tag (EST) analysis approach was undertaken to identify major genes involved in cold acclimation of Rhododendron, a broad-leaf, woody evergreen species. Two cDNA libraries were constructed, one from winter-collected (cold-acclimated, CA; leaf freezing tolerance -53 degrees C) leaves, and the other from summer-collected (non-acclimated, NA; leaf freezing tolerance -7 degrees C) leaves of field-grown Rhododendron catawbiense plants. A total of 862 5'-end high-quality ESTs were generated by sequencing cDNA clones from the two libraries (423 from CA and 439 from NA library). Only about 6.3% of assembled unique transcripts were shared between the libraries, suggesting remarkable differences in gene expression between CA and NA leaves. Analysis of the relative frequency at which specific cDNAs were picked from each library indicated that four genes or gene families were highly abundant in the CA library including early light-induced proteins (ELIP), dehydrins/late embryogenesis abundant proteins (LEA), cytochrome P450, and beta-amylase. Similarly, seven genes or gene families were highly abundant in the NA library and included chlorophyll a/b-binding protein, NADH dehydrogenase subunit I, plastidic aldolase, and serine:glyoxylate aminotransferase, among others. Northern blot analyses for seven selected abundant genes confirmed their preferential expression in either CA or NA leaf tissues. Our results suggest that osmotic regulation, desiccation tolerance, photoinhibition tolerance, and photosynthesis adjustment are some of the key components of cold adaptation in Rhododendron.
 ...
PMID:Comparative analysis of expressed sequence tags from cold-acclimated and non-acclimated leaves of Rhododendron catawbiense Michx. 1593 92

Levels of components of the cytochrome P450 (CYP)-dependent monooxygenase system were characterised in microsomes of major biotransformation tissues, or whole bodies, of 33 species from six phyla of aquatic invertebrates. The phylogenetic distribution of benzo[a]pyrene hydroxylase (BPH) activity in the absence of added NADPH (so-called 'NADPH-independent BPH activity') and presence of NADPH was also examined. Microsomal protein yield was higher in individual tissues than whole tissues. The main components (total CYP and cytochrome b5; NADPH-dependent cytochrome c (CYP) reductase, NADH-dependent cytochrome c reductase and NADH-dependent ferricyanide (b5) reductase activities) were found in most species of the Porifera, Cnidaria, Mollusca, Polychaeta, Crustacea and Echinodermata examined. The so-called '418-peak' of the carbon-monoxide difference spectrum of reduced microsomes was found in all species, indicating the wide distribution of this protein. Total CYP levels (pmol mg(-1) protein; mean+/-SEM) were similar in molluscs (50+/-7), crustaceans (61+/-11) and echinoderms (56+/-9), with the exception of high levels (223-266) in two crustacean species. NADPH-dependent BPH activity (pmol min(-1) mg(-1) protein) was found in 32 species, being lowest in Porifera and Cnidaria (3-4), intermediate in Mollusca (7.8+/-1.3), and highest in Crustacea (25+/-4) and Echinodermata (15+/-4). NADPH-independent BPH activity was evident in 13 out of 15 molluscan species examined, with the addition of NADPH either stimulating (8 species) or inhibiting (5 species) the activity. NADPH-independent BPH activity was also seen in two poriferan species and indicated in three crustacean species, suggesting that the phenomenon is not solely restricted to the Mollusca.
 ...
PMID:Components of the cytochrome P450-dependent monooxygenase system and 'NADPH-independent benzo[a]pyrene hydroxylase' activity in a wide range of marine invertebrate species. 1597 46

This mini-review summarizes results of studies on the oxidation of proteins and low-density lipoprotein (LDL) by various mixed-function oxidation (MFO) systems. Oxidation of LDL by the O2/FeCl3/H2O2/ascorbate MFO system is dependent on all four components and is much greater when reactions are carried out in the presence of a physiological bicarbonate/CO2 buffer system as compared to phosphate buffer. However, FeCl3 in this system could be replaced by hemin or the heme-containing protein, hemoglobin, or cytochrome c. Oxidation of LDL by the O2/cytochrome P450 cytochrome c reductase/NADPH/FeCl3 MFO system is only slightly higher (25%) in the bicarbonate/CO2 buffer as compared to phosphate buffer, but is dependent on all components except FeCl3. Omission of FeCl3 led to a 60% loss of activity. These results suggest that peroxymonobicarbonate and/or free radical derivatives of bicarbonate ion and/or CO2 might contribute to LDL oxidation by these MFO systems.
 ...
PMID:Protein oxidation by the cytochrome P450 mixed-function oxidation system. 1614 Feb 63

The purpose of this investigation was to examine the relationship among hepatic microsomal enzyme induction, liver weight, histological evidence of hepatic injury, and serum clinical chemistry markers of hepatic origin in the cynomolgus monkey. We report here the results from independent toxicology studies for 10 investigative drug candidates representing four therapeutic classes. Study conditions were selected to elicit target organ toxicity. We found that six of the 10 compounds altered cytochrome P450-associated activities in both male and female monkeys, two in females only, and one altered similar activities in males only. Frequently, significant treatment-related elevations in NADPH cytochrome c reductase and ethylmorphine N-demethylase were noted. When the results from all 10 studies were pooled, 14 cytochrome P450-associated activities were significantly increased and five were decreased in males compared to 15 significantly increased and three decreased in the females. Treatment-associated liver weight increases were noted in four studies. Except for hepatocellular hypertrophy in one study, no significant treatment-related microscopic changes in liver and no elevations of serum biomarkers commonly associated with liver toxicity were observed in any of the studies that demonstrated significant hepatic enzyme induction. Compared to parallel rat studies, one compound was an inducer only in monkeys and one was an inducer only in rats. Significant elevations of microsomal drug-metabolizing enzymes in the cynomolgus monkey liver are not accompanied by substantial hepatic changes except for hepatomegaly. These alterations in the hepatic drug-metabolizing enzyme system were benign based the absence of histopathological lesions and serum biomarkers of hepatobiliary toxicity.
 ...
PMID:The relationship among microsomal enzyme induction, liver weight, and histological change in cynomolgus monkey toxicology studies. 1627 8

Addition of U(VI) (uranyl acetate) to isolated rat hepatocytes results in rapid glutathione oxidation, reactive oxygen species (ROS) formation, lipid peroxidation, decreased mitochondrial membrane potential, and lysosomal membrane rupture before hepatocyte lysis occurred. Cytotoxicity was prevented by ROS scavengers, antioxidants, and glutamine (ATP generator). Hepatocyte dichlorofluorescein oxidation was inhibited by mannitol (a hydroxyl radical scavenger) or butylated hydroxyanisole and butylated hydroxytoluene (antioxidants). Glutathione depleted hepatocytes were resistant to U(VI) toxicity and much less dichlorofluorescein oxidation occurred. Reduction of U(VI) by glutathione or cysteine in vitro was also accompanied by oxygen uptake and was inhibited by Ca(II) (a U(IV) or U(VI) reduction inhibitor). U(VI)-induced cytotoxicity and ROS formation was also inhibited by Ca(II), which suggests that U(IV) and U(IV) GSH mediate ROS formation in isolated hepatocytes. The U(VI) reductive mechanism required for toxicity has not been investigated. Cytotoxicity was also prevented by cytochrome P450 inhibitors, particularly CYP 2E1 inhibitors, but not inhibitors of DT diaphorase or glutathione reductase. This suggests that P450 reductase and reduced cytochrome P450 contributes to U(VI) reduction to U(IV). In conclusion, U(VI) cytotoxicity is associated with mitochondrial/lysosomal toxicity by the reduced biological metabolites and ROS.
 ...
PMID:A search for cellular and molecular mechanisms involved in depleted uranium (DU) toxicity. 1684 14

Numerous mutations/polymorphisms of the POR gene, encoding NADPH:cytochrome P450 oxidoreductase (CYPOR), have been described in patients with Antley-Bixler syndrome (ABS), presenting with craniofacial dysmorphogenesis, and/or disordered steroidogenesis, exhibiting ambiguous genitalia. CYPOR is the obligate electron donor to 51 microsomal cytochromes P450 that catalyze critical steroidogenic and xenobiotic reactions, and to two heme oxygenase isoforms, among other redox partners. To address the molecular basis of CYPOR dysfunction in ABS patients, the soluble catalytic domain of human CYPOR was bacterially expressed. WT enzyme was green, due to air-stable FMN semiquinone (blue) and oxidized FAD (yellow). The ABS mutant V492E was blue-gray. Flavin analysis indicated that WT had a protein:FAD:FMN ratio of approximately 1:1:1, whereas approximately 1:0.1:0.9 was observed for V492E, which retained 9% of the WT k(cat)/K(m) in NADPH:cytochrome c reductase assays. V492E was reconstituted upon addition of FAD, post-purification, as shown by flavin analysis, activity assay, and near UV-visible CD. Both Y459H and V492E were expressed as membrane anchor-containing proteins, which also exhibited FAD deficiency. CYP4A4-catalyzed omega-hydroxylation of prostaglandin E1 was supported by WT CYPOR but not by either of the ABS mutants. Hydroxylation activity was rescued for both Y459H and V492E upon addition of FAD to the reaction. Based on these findings, decreased FAD-binding affinity is proposed as the basis of the observed loss of CYPOR function in the Y459H and V492E POR mutations in ABS.
 ...
PMID:Diminished FAD binding in the Y459H and V492E Antley-Bixler syndrome mutants of human cytochrome P450 reductase. 1699 38

TNT (2,4,6-trinitrotoluene) was the most common nitro aromatic explosive available in World War II ammunitions. The presence of ordnance dumped at sea might represent a great concern for marine species living close to dumping sites and the toxicological properties of the chemicals released into the marine environments need to be evaluated. The aim of the present study is to investigate the involvement of CYP (cytochrome P450) system in the metabolism of TNT in marine organisms by using the European eel [Anguilla anguilla (Linnaeus, 1758)] as model species. In vivo exposure to sublethal concentration of TNT (0.5, 1 and 2.5 mg/l) leads to a significant decrease in the phase I CYP1A catalytic activities such as EROD (7-ethoxyresorufin-O-de-ethylase) and MROD (7-methoxyresorufin-O-de-ethylase). On the opposite, a significant increase in NADPH cytochrome c reductase activity as well as phase II UDP-glucuronosyltransferase activity is observed. An inhibition at enzyme level is hypothesized for both CYP1A enzymes, also confirmed by a similar decrease observed after in vitro exposure. An active role of NADPH cytochrome c reductase and phase II enzymes in the TNT metabolism may also be hypothesized.
 ...
PMID:The involvement of cytochrome P450 system in the fate of 2,4,6-trinitrotoluene (TNT) in European eel [Anguilla anguilla (Linnaeus, 1758)]. 1707 91

Expression and monooxygenase activity of various cytochrome P450 (CYP) enzymes along with constitutive androstane (CAR) and the pregnane X (PXR) receptors were investigated in the brain of control and phenobarbital-treated rabbits (80 mg/kg for 4 days). RT-PCR analysis, using specific primers, demonstrated that in control rabbits mRNAs of CYP 2A10, 2B4/5 and 3A6 were expressed, though to a different extent, in the liver, as well as in brain cortex, midbrain, cerebellum, striatum, hippocampus and hypothalamus, whilst CYP2A11 and 4B1 were not expressed in the hypothalamus. CAR was expressed in liver and all the brain regions examined, whereas the PXR was expressed only in liver and cortex. Real time RT-PCR analysis demonstrated that in vivo treatment with phenobarbital, in contrast with what happened in liver, did not induce the expression of CYP 2B4/5 mRNA in cortex, midbrain and cerebellum. NADPH cytochrome c reductase and some other enzymatic activities markers of CYP 2A, 2B, 3A and 4B activities were studied in liver microsomes as well as in microsomes and mitochondria of brain cortex, midbrain and cerebellum of control and phenobarbital-treated rabbits. In contrast to what was observed in liver, phenobarbital treatment did not induce the aforementioned monooxygenase activities in brain. However, we cannot exclude that a longer phenobarbital treatment may lead to a significant induction of CYP activities in brain. These findings indicated that brain CYPs, despite the presence of CAR, were resistant to phenobarbital induction, indicating a possible different regulation of these enzymes between brain and liver.
 ...
PMID:Expression, microsomal and mitochondrial activities of cytochrome P450 enzymes in brain regions from control and phenobarbital-treated rabbits. 1716 34

Earlier observations carried out in our laboratory highlighted the mode of action of acetoxy 4-methylcoumarins and quercetin pentaacetate in preventing the genotoxicity of aflatoxin B1 (AFB1). We have extended the observation to an acetoxy biscoumarin i.e. ellagic acid peracetate (EAPA), which unlike ellagic acid (EA) has demonstrated time-dependent inhibition of liver microsomes catalysed AFB1-epoxidation as measured by AFB1 binding to DNA. EAPA was more potent than EA in preventing bone marrow and lung cells from AFB1-induced genotoxicity. EAPA was acted upon by microsomal acetoxy drug:protein transacetylase (TAase) leading to modulation of the catalytic activity of certain functional proteins (cytochrome P450, NADPH cytochrome c reductase and glutathione S-transferase), possibly by way of protein acetylation.
 ...
PMID:Ellagic acid peracetate is superior to ellagic acid in the prevention of genotoxicity due to aflatoxin B1 in bone marrow and lung cells. 1722 24

The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals.
 ...
PMID:Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat. 1730 Jun 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>