Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of rat hepatocytes for 3 h in a medium containing amino acids, salts and albumin resulted in a 2-fold increase in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. Inclusion of 10% human plasma, rat serum or dialysed rat serum in the medium resulted in an approximate 7-fold increase in reductase activity. These increases were specific since there was little change in the rate of fatty acid synthesis or in the activity of tyrosine aminotransferase. Reductase levels were increased above control values when high density lipoproteins or leithin dispersions were added to the cells. Lecithin dispersions were also shown to increase the rate of efflux of cell cholesterol to the medium. In contrast, reductase levels were reduced when cells were incubated with low density lipoproteins or cholesterol added as an equimolar cholesterol-lecithin dispersion. This inhibition of the reductase by cholesterol dispersions was dependent on the continued de novo protein synthesis. Our data indicate that in normal rat hepatocytes the relative rates of efflux and influx of cholesterol may be critical to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity and cholesterogenesis.
 ...
PMID:Effect of plasma lipoproteins and lecithin-cholesterol dispersions on the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase of isolated rat hepatocytes. 24 22

Because of prominent age-related changes in the responses to stress and in steroid metabolism and excretion, the effect of age on fractionated liver glucocorticoid-binding proteins was studied in C57BL/6J male mice. When cytosol, pre-labeled with [3H]corticosterone, was chromatographed on Sephadex G-100, 4 peaks were obtained. Peak 1 (excluded), peak 2 (corresponding to plasma transcortin), and peak 3 corresponding to glucocorticoid receptors isolated from nuclei) showed no significant age differences. This finding is consistent with reports that glucocorticoid-mediated induction of hepatic tyrosine aminotransferase is not altered by aging in rodents. However, there was a striking age-related decrease (80%) in peak 4 (apparent MW 29,000). Competition studies imply that peak 4 binds aldosterone, testosterone, progesterone, and corticosterone (delta4-3-keto steroids), but not estradiol or dt a plasma component. Although the function of peak 4 is not identified, the pattern of highest competition with delta4-3-keto steroids suggests that it is a steroid ring "A" reductase.
 ...
PMID:Hepatic glucocorticoid binders in mature and senescent C57BL/6J male mice. 127 13

Transcription factor nuclear respiratory factor 1 (NRF-1) was originally identified as an activator of the cytochrome c gene and subsequently found to stimulate transcription through specific sites in other nuclear genes whose products function in the mitochondria. These include subunits of the cytochrome oxidase and reductase complexes and a component of the mitochondrial DNA replication machinery. Here we establish that a functional recognition site for NRF-1 is present in the ATP synthase gamma-subunit gene extending the proposed respiratory role of NRF-1 to complex V. In addition, biologically active NRF-1 sites are found in genes encoding the eukaryotic translation initiation factor 2 alpha-subunit and tyrosine aminotransferase, both of which participate in the rate-limiting step of their respective pathways of protein biosynthesis and tyrosine catabolism. The recognition sites from each of these genes form identical complexes with NRF-1 as established by competition binding assays, methylation interference footprinting, and UV-induced DNA cross-linking. Cloned oligomers of each NRF-1 binding site also stimulate the activity of a truncated cytochrome c promoter in transfected cells. The NRF-1 binding activities for the various target sites copurified approximately 33,000-fold and resided in a single protein of 68 kDa. These observations further support a role for NRF-1 in the expression of nuclear respiratory genes and suggest it may help coordinate respiratory metabolism with other biosynthetic and degradative pathways.
 ...
PMID:Nuclear respiratory factor 1 activation sites in genes encoding the gamma-subunit of ATP synthase, eukaryotic initiation factor 2 alpha, and tyrosine aminotransferase. Specific interaction of purified NRF-1 with multiple target genes. 134 57

Growth hormone (GH) may directly affect the expression of some liver cytochromes P-450 inducible by xenobiotics, but this has been difficult to establish with pituitary ablation in living animals. Therefore, we incubated adult rat hepatocytes on a laminin-rich matrix, matrigel, a new system that permits hepatocytes to respond to xenobiotics with induction of the microsomal hemoproteins, the cytochromes P-450, in culture as they do in the intact liver (Schuetz, E. G., Li, D., Omiecinski, C. J., Muller-Eberhard, U., Kleinman, H. K., Elswick, B., and Guzelian, P. S. (1988) J. Cell. Physiol. 134, 309-323). Indeed, when cultures were treated with phenobarbital, there was a rise in mRNAs for the cytochromes P-450b/e and P-450p accompanied by a rise in mRNA for 5-aminolevulinate synthase, the rate-limiting enzyme in heme biosynthesis. Analysis of nuclei from the matrigel cultures established that phenobarbital treatment had activated transcription of the P-450b/e gene. Co-incubation of the cultures with physiologic concentrations of growth hormone completely blocked the induction of these P-450 mRNAs and partially blocked the rise in 5-aminolevulinate synthase mRNA. Induction of P-450p by isosafrole also was inhibited strongly by GH, whereas P-450p induction by pregnenolone 16 alpha-carbonitrile or dexamethasone was affected only weakly by GH. The effect of GH was specific inasmuch as phenobarbital-inducible expression of P-450 reductase, glucocorticoid-inducible expression of tyrosine aminotransferase, and basal expression of albumin were unaffected by the presence or absence of growth hormone. Nuclear analysis revealed that growth hormone inhibited phenobarbital-induced P-450b/e gene transcription, whereas the hormone was without effect on transcription of the liver-specific gene, tyrosine aminotransferase. In contrast, the addition of another peptide hormone, insulin-like growth factor I, was without inhibitory effect on P-450 gene expression. We conclude that growth hormone acts specifically and selectively in direct contact with the hepatocyte to control xenobiotic induction of some liver drug-metabolizing enzymes.
 ...
PMID:Regulation of cytochrome P-450b/e and P-450p gene expression by growth hormone in adult rat hepatocytes cultured on a reconstituted basement membrane. 168 52

NADPH-cytochrome-c (P-450) reductase, a flavoprotein, is a constituent of the hepatic microsomal polysubstrate monooxygenase and catalyzes the transfer of electrons from NADPH to cytochrome P-450. The hormonal regulation of NADPH-cytochrome-c reductase activity and protein has been examined in insolated hepatocytes cultured as monolayers for 48 h in Waymouth's MB752/1 medium fortified with insulin, dexamethasone and triiodothyronine. No similarity between the response of NADPH-cytochrome-c reductase and of tyrosine aminotransferase and malate dehydrogenase activity to dexamethasone and triiodothyronine treatment could be detected. In the absence of hormones about 65% of the original NADPH-cytochrome-c reductase activity and protein estimated by the immunochemical staining technique was retained. Culture of hepatocytes in insulin (10.0 mU/ml) or dexamethasone (100 nM) alone but not triiodothyronine improved the retention of reductase activity and protein. Only when hepatocytes were cultured in insulin, triiodothyronine and dexamethasone could NADPH-cytochrome-c reductase activity and protein be maintained at the original level. Dexamethasone alone was found to enhance consistently retention of reductase protein, but not reductase activity, to approximately the same level as in freshly isolated hepatocytes. The results suggest that microsomal NADPH-cytochrome-c reductase activity and protein can be maintained in isolated hepatocytes at the original level by culturing the cells in dexamethasone, insulin and triiodothyronine.
 ...
PMID:The effect of dexamethasone, insulin and triiodothyronine on microsomal NADPH-cytochrome-c (P-450) reductase in primary cultures of isolated hepatocytes. 288 91

Late gestation foetus from rats fed a non-absorbable bile acid binding resin (cholestyramine) have increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. This was due to increased unphosphorylated (active) as well as total reductase and was accompanied by higher fatty acid synthetase activity. No increase in foetal hepatic cystathionase or tyrosine aminotransferase activity, or changes in plasma insulin, corticosterone or thyroxine were found. The studies demonstrate that foetal hepatic cholesterol metabolism is sensitive to drug-induced perturbation of maternal lipoprotein metabolism. The data suggest induction of foetal cholesterol and fatty acid synthesis by a specific mechanism not involving generalized hormone-induction of hepatic enzyme systems. Cholestyramine appears to have application for in vivo study of the regulation of foetal cholesterologenesis and its coordination to maternal and foetal steroid requirements.
 ...
PMID:Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in foetal rats by maternal cholestyramine feeding. 306 40

A rapid spectrophotometric method for estimation of tyrosine aminotransferase activity (TAT) is described, based on a coupled reaction with NADH-dependent aromatic ketoacid reductase. 3-iodo-L-tyrosine, upon TAT action, is transformed into 3-iodo-4-hydroxyphenylpyruvate which quickly reacts with NADH in the presence of aromatic ketoacid reductase; oxidation rates at 340 nm are linear with protein concentration over the whole range of purification steps of TAT. This new method, for its sensitivity, easy performance and possibility of a continuous monitoring of TAT reaction, may be considered comparable to the more diffuse spectrophotometric standard method, and also as an alternative, advantageous procedure in some instances. The method for purification of the coupled aromatic ketoacid reductase is also described.
 ...
PMID:NADH-coupled spectrophotometric assay of tyrosine aminotransferase. 611 76

Cytochrome P-4503A, CYP2B, and P-450 reductase are induced by glucocorticoids, antiglucocorticoids such as pregnenolone 16alpha-carbonitrile, and drugs such as rifampin and phenobarbital. Although the pregnane X receptor is reported to mediate steroid and drug activation of CYP3A via a conserved cis-element in CYP3A genes, discrepancies exist between the induction of the endogenous CYP3A genes and the activation of the pregnane X receptor. It is a formal possibility that the glucocorticoid receptor may account for some of these discrepancies. To determine the requirement in vivo of the glucocorticoid receptor in expression of CYP3A and CYP2B, we compared the induction of these proteins in the livers of normal mice and mice with a targeted mutation in the glucocorticoid receptor. Mice lacking the glucocorticoid receptor show no difference in constitutive hepatic expression of CYP3A but show a decrease in the level of CYP2B. Glucocorticoid receptor-deficient mice challenged with either dexamethasone or pregnenolone 16alpha-carbonitrile failed to induce CYP2B proteins, whereas CYP2B was readily induced in (+/+) mice. In contrast, CYP3A and P-450 reductase proteins were induced by either inducer in wild-type and glucocorticoid receptor-null mice. Similarly, rifampin induced CYP3A in either wild-type or glucocorticoid receptor-null mice. Despite reports that rifampin is a nonsteroidal ligand for the human glucocorticoid receptor, rifampin failed to induce tyrosine aminotransferase in mice regardless of glucocorticoid receptor genotype, and rifampin did not compete for ligand binding to either mouse or human glucocorticoid receptor. Phenobarbital induced CYP3A, CYP2B, and P-450 reductase in all mice, but the amplitude of induction was diminished 37% in glucocorticoid receptor-null mice. Thus, there are distinctly different essential requirements of CYP3A, CYP2B, and P-450 reductase genes for the glucocorticoid receptor in their induction by steroids and drugs.
 ...
PMID:The glucocorticoid receptor is essential for induction of cytochrome P-4502B by steroids but not for drug or steroid induction of CYP3A or P-450 reductase in mouse liver. 1068 70

Coronatine-inducible tyrosine aminotransferase (TAT), which catalyses the transamination from tyrosine to p-hydroxyphenylpyruvate, is the first enzyme of a pathway leading via homogentisic acid to plastoquinone and tocopherols, the latter of which are known to be radical scavengers in plants. TAT can be also induced by the octadecanoids methyl jasmonate (MeJA) and methyl-12-oxophytodienoic acid (MeOPDA), as well as by wounding, high light, UV light and the herbicide oxyfluorfen. In order to elucidate the role of octadecanoids in the process of TAT induction in Arabidopsis thaliana (L.) Heynh., the jasmonate-deficient mutant delayed dehiscence (dde1) was used, in which the gene for 12-oxophytodienoic acid reductase 3 is disrupted. The amount of immunodetectable TAT was low. The enzyme was still fully induced by coronatine as well as by MeJA although induction by the latter was to a lesser extent and later than in the wild type. Treatment with MeOPDA, wounding and UV light, however, had hardly any effects. Tocopherol levels that showed considerable increases in the wild type after some treatments were much less affected in the mutant. However, starting levels of tocopherol were higher in non-induced dde1 than in the wild type. We conclude that jasmonate plays an important role in the signal transduction pathway regulating TAT activity and the biosynthesis of its product tocopherol.
 ...
PMID:Jasmonate is involved in the induction of tyrosine aminotransferase and tocopherol biosynthesis in Arabidopsis thaliana. 1243 28

The SufI protein and the trimethylamine N-oxide reductase (TorA) are the two best-characterized prototype proteins exported by the Escherichia coli TAT system. Whereas SufI does not contain cofactors, TorA is a molybdo-enzyme and the acquisition of the molybdo-cofactor is a prerequisite for its translocation. The overproduction of each protein leads to the saturation of its translocation, but it was unknown if the overproduction of one substrate could saturate the TAT apparatus and block thus the translocation of other TAT substrates. Here, we showed that the overproduction of SufI saturated only its own translocation, but had no effect of the translocation of TorA and other TAT substrate analyzed. To dissect the saturation mechanism of TorA translocation, we shortened by about one-third of the TorA protein and removed nine consensus molybdo-cofactor-binding ligands. Like SufI, the truncated TorA (TorA502) did not contain cofactor and would not compete with the full length TorA for molybdo-cofactor acquisition. The overproduction of TorA502 completely inhibited the export of the full length TorA and dimethyl sulfoxide (DMSO) reductase, but had no effect on the translocation of SufI, nitrate-induced formate dehydrogenase and hydrogenase-2. Importantly, deletion of the twin-arginine signal peptide of TorA502 abolished the inhibitory effect. Moreover, the overproduction of the TorA signal peptide fused to the green fluorescence protein (GFP) was sufficient to block the TorA translocation. These results demonstrated that the twin-arginine signal peptide of the TorA protein specifically inhibits the translocation of a subset of TAT substrates, probably at the step of their targeting to the TAT apparatus.
 ...
PMID:Specific inhibition of the translocation of a subset of Escherichia coli TAT substrates by the TorA signal peptide. 1263 52


1 2 3 Next >>