Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of certain drug metabolizing enzymes have been measured in liver and kidney slice preparations from domesticated birds. Aminopyrine demethylase activity was significantly lower in liver slices from the duck (Aylesbury X Pekin, Khaki-Campbell) than from the rat (Wistar), and in the Aylesbury X Pekin duck lower than in the turkey (Triple 6 FLX), chicken (Brown Leghorn, Rhode Island Red X Light Sussex) and goose (Emden X Doulouse). The microsomal cytochrome P-450 was lower in duck liver (Aylesbury X Pekin) than in rat liver, and the aniline hydroxylase and aminopyrine demethylase activities in a 10,000 g supernatant fraction of liver were lower in duck preparations (Aylesbury X Pekin, Khaki-Campbell) than rat preparations. These observations suggest that the duck is likely to be susceptible to drugs which are metabolized by the cytochrome P-450 containing mono-oxygenases. UDP-Glucuronyl transferase activity was not detectable in liver and kidney slices from two mature geese. This observation was not the outcome of a deficiency of UDP-glucuronic acid, rapid breakdown of glucuronide by beta-glucuronidase or the presence of a substance inhibitory to UDP-glucuronyl transferase. Liver slices from geese, ducks (Aylesbury X Pekin) and chickens contained low UDP-glucuronyl transferase and high sulphate conjugation enzyme activities, whereas the reverse was found in Khaki-Campbell ducks. The activities of UDP-glucuronyl transferase and the sulphate conjugation enzymes were both relatively high in liver slices from the turkey and rat. The kidney contained lower enzyme activities than the liver except in the duck (Aylesbury X Pekin), in which low activities of aminopyrine demethylase and UDP-glucuronyl transferase were present in slices of both organs. In liver slices from chickens and geese the activities of aminopyrine demethylase and the sulphate conjugation enzymes were similar in mature and immature birds, and the activity of UDP-glucuronyl transferase was considerably higher in chicks and goslings than in mature birds of the same species. In the chick the activities of aminopyrine demethylase, UDP-glucuronyl transferase and the sulphate conjugation enzymes were higher in the duodenum than the remainder of the alimentary tract. The activities of these enzymes in pieces of duodenum were as high as those in slices of liver. The inclusion of sulphate in the incubation medium produced a significant increase in the synthesis of p-nitrophenyl sulphate in liver slices and not kidney slices except those from the duck. The kidney slices seemed to produce sufficient sulphate for the reaction of the sulphate conjugation enzymes to proceed at the maximum rate, but the liver slices did not do so.
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PMID:Activities of mixed function oxidases, UDP-glucuronyl transferase and sulphate conjugation enzymes in galliformes and anseriformes. 81 57

The lineage and state of differentiation of cells in the mammalian haemopoietic compartment is associated with specific patterns of homeobox gene expression (EMBO J. 7, 2131, 1988). Agents which influence homeobox gene expression are thus of great interest in the study of human leukemias. Retinoic acid has direct regulatory actions on homeobox gene transcription (TIBS 158, 52, 1989; Differentiation 37, 773, 1988) and can induce select human leukemia cell lines to undergo terminal differentiation in vitro (Proc. natl Acad. Sci. U.S.A. 77, 2936, 1980). Retinoic acid is also a known teratogen for vertebrate foetal limb-bud development. Some of the teratogenic effects are duplicated by the drug Thalidomide (Embryopathic Activity of Drugs, Little Brown, Boston, p. 167, 1965; Haematological Cytology, Wolf Med. Pub. Ltd, London, p. 118, 1982). To investigate Thalidomide for other retinoid-like effects, we exposed cultures of human leukemia K562 cells to the metabolites generated in a Thalidomide hepatic-microsomal enzyme drug metabolizing system (Proc. natl Acad. Sci. U.S.A. 78, 2545, 1981). Here we report evidence that a single 2 h pulse-exposure to Thalidomide metabolites, induces K562 cells to undergo morphological differentiation in vitro. We also demonstrate a significant cytotoxic effect for these metabolites.
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PMID:Induction of morphological differentiation in the human leukemic cell line K562 by exposure to thalidomide metabolites. 201 4

The umu test system is a newly developed method to evaluate genotoxicities of a wide variety of environmental carcinogens and mutagens (Oda et al., 1985; Nakamura et al., 1987). In the present study, SOS-inducing activity of 142 synthetic dyes was investigated by the umu test using Salmonella typhimurium (TA1535/pSK1002) under the condition of absence and presence of rat liver microsomal fraction. The samples showing a beta-galactosidase activity of more than 1.5 fold over the background level were reexamined and the dose-response curves were prepared at various doses. Then, the samples showing beta-galactosidase activity of more than 1.5-fold of the background level were defined as genotoxic. Among the synthetic dyes examined, 11 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Acid Black 26, Acid Black 50, Acid Brown 2, Disperse Red 73, Disperse Red 145, Disperse Red 157, Disperse Violet 52, Reactive Red 110, Reactive Yellow 13 and Reactive Yellow 75, and in the presence of S9, Reactive Blue 147 was judged to be genotoxic. An evident dose-response relationship was observed between the doses of the dye and umu-gene expression in these 11 dyes.
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PMID:[Genotoxicity of synthetic dyes in umu test using Salmonella typhimurium TA1535/pSK1002 (1). Results of examination for acid dyes, direct dyes, disperse dyes and reactive dyes]. 211 88

In the present study, SOS-inducing activity of 76 basic dyes was investigated by umu test using Salmonella typhimurium TA1535/pSK1002 under the condition of absence and presence of rat liver microsomal fraction. The test was carried out with five doses of basic dyes (400, 120, 40, 12, and 4 micrograms/ml). The samples showing beta-galactosidase activity more than 1.5-fold over the background level were reexamined and the dose-response curves were prepared at various doses. Thereafter, samples showing beta-galactosidase activity unit more than 1.5-fold of the background level were defined as genotoxic. Among the basic dyes examined, 13 compounds induced umu gene expression. The potent genotoxic compounds without metabolic activation were Blue 40, Blue 47, Brown 14, Orange 30, Red 24, Violet 30, Violet 31, Yellow 13(h), Yellow 19, Yellow 25, Yellow 67, and Yellow 73 and in the presence of S9, Orange 47 was judged as genotoxic in addition to the aforementioned dyes. An evident dose-response relationship between the doses of the dye and umu gene expression was observed in these 13 dyes.
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PMID:[Genotoxicity of synthetic dyes in the umu test using Salmonella typhimurium TA1535/pSK1002 (II). Results of examination of basic dyes]. 227 83

The release of mutagens from 7 carbon black-based leather dyes and from leather samples at various stages of finishing was determined. After vigorous treatment with toluene, 4 commercial dyes yelded mutagenic extracts on Salmonella typhimurium in the presence of microsomal enzymes. Only in one case were the responsible chemicals identified as polycyclic aromatic hydrocarbons. The low bioavailability of mutagens contained in carbon black and their low mutagenic activity suggest that the risk associated with the use of these dyes is probably negligible. Soxhlet extracts with ethanol from finished leather were mutagenic on strain TA98 of Salmonella typhimurium in the absence of S9 mix. Analysis of extracts of leather samples at various intermediate stages of processing showed that mutagenic activity was detectable after the colouring process. The responsible compound was identified as a nitroazo dye (Colour Index: Acid Brown 83), with a mutagenic potential of about 4 revertant/micrograms. Eighteen commercial tannins containing mainly Cr(III) sulphates were assessed for genotoxicity. Most were contaminated with Cr(VI), a known mutagenic and carcinogenic agent, at levels sufficient to induce an increased frequency of SCE (sister chromatid exchanges) in mammalian cells (CHO, chinese hamster ovary) tested in vitro.
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PMID:[Identification of genotoxic compounds used in leather processing industry]. 227 96

Liver microsomal 3-hydroxy-3-methylglutaryl-CoA reductase was partially purified from cholestyramine-fed rats by sequential extraction of the membrane with 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and polyethylene glycol nonylphenyl ether (Triton N-101) and solubilized by incorporation of the resulting insoluble protein preparation into a detergent mixture of Triton N-101 and sodium N-lauroylsarcosinate (Sarkosyl) in the presence of high salt. The purification procedure resulted in approximately a 3-4-fold increase in specific activity compared with the microsomal fraction, and the enzyme was recovered with yields as high as 63%. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and a blotting experiment using antiserum to the purified 53,000-dalton reductase fragment showed that the major immunoreactive polypeptide had a Mr of 97,000, that expected for the native intact form of the enzyme (Chin, D. J., Gil, G., Russell, D. W., Liscum, L., Luskey, K. L., Basu, S. K., Okayama, H., Berg, P., Goldstein, J. L., and Brown, M. S. (1984) Nature 308, 613-617). In addition, the effect of various detergents on the activity and stability of the membrane-bound and the partially purified enzyme was determined, and a method for protection of the reductase from inactivation caused by the addition of anionic detergents to the assay mixture is described.
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PMID:Solubilization of the 97-kDa native form of liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A reductase. 235 84

We have recently described a monoclonal antibody (1F8) that recognizes a form of glucose transporter unique to fat and muscle (James, D. E., Brown, R., Navarro, J., and Pilch, P. F. (1988) Nature 333, 183-185), tissues that respond acutely to insulin by markedly increasing their glucose uptake. Here, we report that rat adipocytes possess two immunologically distinct glucose-transporters: one recognized by 1F8, and one reactive with antibodies raised against the human erythrocyte glucose transporter. Immunoadsorption experiments indicate that these glucose transporters reside in different vesicle populations and that both transporter isoforms translocate from intracellular sites to the plasma membrane in response to insulin. The insulin-regulatable transporter resides in a unique vesicle that comprises 3% or less of the low density microsomes of fat cells and has a limited protein composition that does not include the bulk of another translocatable protein, the insulin-like growth factor II receptor. Immunoprecipitation with 1F8 of microsomal glucose transporters photoaffinity labeled with [3H]cytochalasin B brings down 90% of the label. Similarly, immunoprecipitation with 1F8 of glucose transporters from insulin-stimulated plasma membranes photolabeled with 3-[125I]iodo-4-azidophenethylamido-7-O-succinyldeacetyl-f ors kolin, another transporter-selective reagent, results in 75% of the labeled transporter localized in the immunoprecipitate. Thus, insulin action involves the combined effect of translocation from at least two vesicle pools each containing different glucose transporters. The 1F8-reactive transporter comprises the majority of the total transporter pool that is responsible for the insulin-induced increase in glucose transporter number.
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PMID:Insulin-regulated glucose uptake in rat adipocytes is mediated by two transporter isoforms present in at least two vesicle populations. 254 7

The levels of expression of cytochromes P-450b and P-450e (both inducible by phenobarbital (PB) and differing by only 14 of 491 amino acids) in liver microsomes from untreated male rats were separately quantitated by Western blotting with a polyclonal antibody raised against P-450b that is equally effective against P-450e (anti P-450b/e). A protein with mobility identical to P-450e was detected in all microsomal samples. Microsomes from uninduced livers of individual male rats from five different strains exhibited only minor interstrain and interindividual variability in the expression of P-450e (17 +/- 5 pmol P-450e/mg microsomal protein) with the exception of the Brown Norway strain (8.5 +/- 0.5 pmol P-450e/mg). Expression of P-450b varied widely from undetectable levels (less than 2 pmol/mg) in most Sprague-Dawley rats to about 50% of P-450e levels in Fischer and Brown Norway strains. Anti P-450b/e inhibited total metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) by uninduced microsomes, to an extent dependent on rat strain (15-30%), predominantly through inhibition of formation of 12-hydroxymethyl-7-methyl BA (12HOMMBA) (65-85%), the major metabolite of purified P-450e. A specific activity for P-450e-dependent DMBA metabolism was calculated from four sets of microsomes where the P-450b content was either undetectable or very low (0.7-1.0 nmol/nmol P-450e/min-1). Comparable calculated activities were, however, obtained from other untreated rat liver microsomes where P-450b levels were significant. Polymorphism in P-450b was detected but did not affect total P-450b expression or the sensitivity of DMBA metabolism to anti P-450b/e. A fourth band of greater mobility than P-450b (apparent Mr less than 50,000), was also recognized by anti P-450b/e. The intensity of this band did not vary among individual rats or among the different strains and therefore did not correlate with the sensitivity of microsomal DMBA metabolism to anti P-450b/e. A monoclonal antibody (MAb) against P-450b (2-66-3) recognized P-450's b, b2, and e on Western blots but did not react with this higher mobility band. MAb 2-66-3 and two other MAbs produced against P-450b inhibited 12-methylhydroxylation of DMBA by untreated rat liver microsomes to the same extent as anti P-450b/e. Following PB induction, P-450b was induced to about double the level of P-450e in most rat strains examined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential expression and function of three closely related phenobarbital-inducible cytochrome P-450 isozymes in untreated rat liver. 311 33

The Katholiek substrain of Brown Norway (BN/Kat) rats exhibits a very low level of circulating high-molecular-mass (HMW) kininogen and a partial deficiency in plasma prekallikrein. Northern blot analysis of liver RNA revealed that HMW kininogen and prekallikrein mRNAs are present in these rats with a similar size and abundance compared to control Brown Norway (BN/Orl) rats. The low-molecular-mass kininogen mRNA, encoded by the same kininogen gene as HMW kininogen mRNA by alternative splicing, is detected in both strains by dideoxynucleotide limited primer extension analysis. Measurement of HMW kininogen by radioimmunoassay was performed in liver subcellular fractions. It reveals that, in contrast to its absence in the cytosolic fraction, HMW kininogen in deficients rats is slightly more abundant in the microsomal fraction, than in control rats. These observations exclude both an abnormality at the level of gene transcription and a major structural modification of the transcribed RNA and of the synthesized HMW kininogen. They favour the hypothesis of an abnormal intracellular transport of the HMW kininogen in deficient rats.
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PMID:The high-molecular-mass kininogen deficient rat expresses all kininogen mRNA species, but does not export the high-molecular-mass kininogen synthesized. 318 25

The clearance of many oxidized drugs falls with age. Whilst factors such as reduced liver size, blood flow and specific enzyme activity may be important, the possibility that reduced enzyme affinity for substrate contributes to this fall has not hitherto been investigated. Using liver microsomes from 12 young adult and 12 elderly male Norwegian Brown rats we defined the kinetics of ethoxyresorufin-O-de-ethylation and aldrin epoxidation, specific substrates for the 3-methylcholanthrene inducible and phenobarbitone inducible forms of cytochrome P450, respectively. Our results show a marked fall in the maximal activity of both enzymes in advanced age whether expressed in terms of microsomal protein or unit of cytochrome P450, but with no change in apparent enzyme affinity (Km). Since Km is unchanged, we feel that qualitative age-related changes in cytochrome P450 are unlikely. Reduced metabolism may be due to age-related alterations in coenzymes or smooth endoplasmic reticulum lipid membranes.
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PMID:The effect of age on mono-oxygenase enzyme kinetics in rat liver microsomes. 360 96


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