Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Phenobarbitone in a dose of 180 mg daily was administered to ten normal subjects for 3 weeks. There was a significant increase in total plasma cholesterol, plasma low-density-lipoprotein cholesterol, plasma low-density-lipoprotein (LDL) triglycerides and plasma LDL protein. The increase in plasma LDL cholesterol accounted for the increase in total plasma cholesterol. There was a significant reduction in the ratio of LDL cholesterol to LDL protein. 2. No significant changes were observed in total plasma triglycerides, plasma very-low-density-lipoprotein (VLDL) triglycerides, plasma VLDL cholesterol or plasma VLDL protein. 3. Evidence that drug-metabolizing enzymes were induced by phenobarbitone was provided by an increase in antipyrine clearance. No relationship was observed between changes in plasma cholesterol and changes in antipyrine clearance. Serum gamma-glutamyl transpeptidase was also increased after phenobarbitone administration, the increase being unrelated to changes in antipyrine clearance or plasma cholesterol.
Clin Sci Mol Med 1976 May
PMID:Effect of phenobarbitone on plasma lipids in normal subjects. 0 82

1. Highly sensitive technique are described for the assay of plasma membrane (5'-nucleotidase, alkaline phosphatase), microsomal (neutral alpha-glucosidase, leucyl-2-naphthylamidase) and biliary canalicular (gamma-glutamyltransferase) enzymes and for nine acid hydrolases (acid phosphatase, phosphodiesterase, beta-glucosidase, alpha-glucosidase, alpha-galactosidase, beta-galactosidase, alpha-mannosidase, N-acetyl-beta-glucosaminidase, beta-glucuronidase) in human liver. 2. Optimum and specific assay systems have been developed which give linear kinetics for all enzymes. 3. The range of enzyme activities in samples of human liver, obtained by closed needle biopsy, and sera have been determined.
Clin Sci Mol Med 1977 Mar
PMID:Enzyme activities in human liver biopsies: assay methods and activities of some lysosomal and membrane-bound enzymes in control tissue and serum. 1 4

1. Enterocytes, isolated from the proximal jejinum and distal ileum of the rat, were homogenized and their organelles separated by isopycnic centrifugation on continuous sucrose density gradients. The distributions of marker enzymes for the principal organelles, RNA and protein were determined in the sucrose gradients and related to the activities per entercocyte. 2. In the jejunum the modal equilibrium densities of the various organelles were: brush borders (1.20), lysosomes (1.20), peroxisomes (1.19), mitochondria (1.17) and basal-lateral membranes (1.13). The values were not significantly different in the ileum. The activities of brush-border enzymes, soluble and mitochondrial malate dehydrogenase, soluble and membrane-associated lactate dehydrogenase and particulate protein content, however, were greater in the jejunal than the ileal enterocytes. 3. Detergent exposed latent alkaline phosphatase activity in jejunal enterocytes and indicated that this enzyme is present not only in the brush border but also in the basal-lateral membrane and soluble fractions of the cell. 4. Isolated jejunal brush-border preprations showed latent activities of both alkaline phosphatase and gamma-glutamyltransferase whereas the activities of alpha-glucosidase and leucyl-beta-naphylamidase were not affected by detergent. Mechanical disruption of these preparations suggested the presence of two forms of alkaline phosphatase in the brush border and provides a technique to assess membrane fragility.
Clin Sci Mol Med 1978 Aug
PMID:Analytical subcellular fractionation studies on enterocytes from the jejunum and ileum of the rat and some properties of brush-border alkaline phosphatase. 2 95

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
Virchows Arch B Cell Pathol Incl Mol Pathol 1979 Jun 29
PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

1. Homogenates of guinea-pig left ventricle were fractionated by differential pelleting and by centrifugation on continuous sucrose density gradients. 2. The principal subcellular organelles of myocardium, characterized by their marker enzyme content, were resolved by density gradient centrifugation in a small-volume zonal rotor. The equilibrium densities (p) of the principal organelles are (with marker enzymes in parentheses): sarcolemma, 1-12 (5'-nucleotidase); lysosomes, 1-16 (N-acetyl-beta-glucosaminidase); mitochondria, 1-17 (cytochrome oxidase); peroxisomes, 1-18 (catalase); cytosol (lactate dehydrogenase). 3. The subcellular distribution of various adenosine triphosphatase activities and previously unassigned enzymes was determined. Leucyl-beta-naphthylamidase and gamma-glutamyl transpeptidase showed both cytosol and sarcolemma components. Ca2+-dependent adenosine triphosphatase showed dual localization to the mitochondria and to the sarcolemma.
Clin Sci Mol Med 1977 Jul
PMID:Analytical subcellular fractionation of guinea-pig myocardium. 14 54

In rats, gamma-glutamyl transpeptidase (gamma GT) exists as a single-copy gene, and three distinct species of RNA (types I, II, and III) that differ in their 5' untranslated regions have been identified. To compare steady-state levels of these gamma GT RNAs in rat tissues, hepatic carcinomas, and cultured cells, we used RNA dot-blot hybridization and a reverse transcriptase-polymerase chain reaction (RT-PCR) technique with oligonucleotides specifically designed for each type of RNA. Fetal liver, hepatic carcinomas, rasT24-transformed rat liver epithelial (RLE) cells and pancreas make only type III RNA. Liver and untransformed RLE cells do not make detectable levels of gamma GT RNA. We found that both fetal and adult kidneys synthesize all three types of RNA, indicating that increases in gamma GT RNA known to occur after birth do not result from recruitment of additional RNA species. When we increased the sensitivity of the assay approximately 1000 fold by sequencing the RT-PCR product directly after an additional round of amplification, we found that very low levels of types I and II RNA were present in fetal liver, rasT24-transformed RLE cells, and pancreas, and that adult liver and untransformed RLE cells synthesized very low levels of all three RNA species. Rat-1 fibroblasts did not make levels of gamma GT RNA detectable by this method. These results demonstrate that different gamma GT RNA species are regulated differently during development and neoplastic transformation and that there is a commitment in some cell types to very-low-level expression of gamma GT RNAs.
Mol Carcinog 1992
PMID:The same gamma-glutamyl transpeptidase RNA species is expressed in fetal liver, hepatic carcinomas, and rasT24-transformed rat liver epithelial cells. 134 50

Plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of 125I-labeled bovine serum albumin, 51Cr-labeled erythrocytes and Evans blue dye from peripheral circulation into the brain. Isolated cerebral microvessels which were characterized in terms of their morphology under scanning electron microscope and enhancement of the specific activities of biochemical markers, viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase, showed significant decrease in these activities due to P. yoelii nigeriensis infection. On the other hand, relatively minor (statistically insignificant) changes occurred in the first two enzyme specific activities in the cerebral cortex and monoamine oxidase registered an increase in this tissue due to infection. Histological examination of the cerebral tissue of infected animals by light and electron microscopy showed broken blood vessel walls and leakage of erythrocytes into extravascular space, some of which contained intraerythrocytic malarial parasite in a state of cell division.
Exp Mol Pathol 1992 Aug
PMID:Aberrations in cerebral vascular functions due to Plasmodium yoelii nigeriensis infection in mice. 135 26

Homogenates and plasma membranes were isolated from the livers of male Fischer 344 rats ranging in age from 19 hr to 92 days postnatal. These plasma membranes exhibited comparable levels of purity: protein yields were 2-2.5%; relative specific activities of 5'-nucleotidase and ouabain-sensitive Na+/K(+)-ATPase were from 8-11 and from 12-19, respectively. 5'-nucleotidase and ouabain-sensitive Na+ K(+)-ATPase displayed distinct and different developmental patterns. The activity of gamma-glutamyltranspeptidase was found to be at exceptionally high levels in isolated plasma membranes immediately after birth and to decline precipitously thereafter achieving and maintaining low levels from days 3-21 postnatal. Liver plasma membrane gamma-glutamyltranspeptidase activity was observed to increase 9.2 fold from this low point, first rising on day 21, peaking on day 40 and returning to low levels by day 56. From day 56 day to 92 postnatal, gamma-glutamyltranspeptidase activity was expressed at a uniformly low level but a level 2 fold higher than that preceding the rise at day 40. The hormone determinants of these developmental changes in gamma-glutamyltranspeptidase activity are discussed.
Mol Cell Biochem 1992 Sep 22
PMID:An extended developmental study of gamma-glutamyltranspeptidase in rat liver plasma membranes: identification of specific patterns of changes in activity in the adult as well as the neonatal state. 135

Thyroid hormone response elements (T3REs) have been identified in a variety of promoters including those directing expression of rat GH (rGH), alpha-myosin heavy chain (rMHC), and malic enzyme (rME). A detailed biochemical and genetic analysis of the rGH element has shown that it consists of three hexamers related to the consensus [(A/G)GGT(C/A)A]. We have extended this analysis to the rMHC and rME elements. Binding of highly purified thyroid hormone receptor (T3R) to T3REs was determined using the gel shift assay, and thyroid hormone (T3) induction was measured in transient tranfections. We show that the wild type version of each of the three elements binds T3R dimers cooperatively. Mutational analysis of the rMHC and rME elements identified domains important for binding T3R dimers and allowed a direct determination of the relationship between T3R binding and function. In each element two hexamers are required for dimer binding, and mutations that interfere with dimer formation significantly reduce T3 induction. Similar to the rGH element, the rMHC T3RE contains three hexameric domains arranged as a direct repeat followed by an inverted copy, although the third domain is weaker than in rGH. All three are required for full function and T3R binding. The rME T3RE is a two-hexamer direct repeat T3RE, which also binds T3R monomer and dimer. Across a series of mutant elements, there was a strong correlation between dimer binding in vitro and function in vivo for rMHC (r = 0.99, P less than 0.01) and rME (r = 0.67, P less than 0.05) T3REs. Our results demonstrate a similar pattern of T3R dimer binding to a diverse array of hexameric sequences and arrangements in three wild type T3REs. Addition of nuclear protein enhanced T3R binding but did not alter the specificity of binding to wild type or mutant elements. Binding of purified T3R to T3REs was highly correlated with function, both with and without the addition of nuclear protein. T3R dimer formation is the common feature which defines the capacity of these elements to confer T3 induction.
Mol Endocrinol 1992 Apr
PMID:Capacity for cooperative binding of thyroid hormone (T3) receptor dimers defines wild type T3 response elements. 158 20

The suspect human hepatocarcinogen aflatoxin B1 (AFB1) is a well-known potent initiator of hepatic tumors in rainbow trout (Oncorhynchus mykiss). Both hepatocellular carcinomas and mixed hepatocellular/cholangiocellular carcinomas are induced by AFB1 in trout, with the mixed form predominating. We previously isolated two c-ras genes from trout liver cDNA, and in the present study we analyzed DNA from 14 AFB1-induced trout liver tumors for point mutations in exon 1 of both genes. Using the polymerase chain reaction (PCR) and oligonucleotide hybridization methods, a high proportion (10/14) of the AFB1-initiated tumor DNAs showed evidence of activating point mutations in the trout c-Ki-ras gene. Of the 10 mutant ras genotypes, seven were codon 12 GGA----GTA transversions, two were codon 13 GGT----GTT transversions, and one was codon 12 GGA----AGA transition. Nucleotide sequence analysis of cloned PCR products from four of these tumor DNAs provided definitive evidence for two codon 12 GGA----GTA mutations, one codon 12 GGA----AGA mutation, and one codon 13 GGT----GTT mutation, in complete agreement with the oligonucleotide hybridization results. No mutations were detected in exon 1 of a second trout ras gene also expressed in liver, nor in DNA from control livers. This is the first report of experimentally induced ras gene point mutations in a lower vertebrate fish model. The results indicate that the hepatocarcinogen AFB1 induces c-Ki-ras gene mutations in trout similar to those in rat liver tumors.
Mol Carcinog 1991
PMID:Analysis of ras gene mutations in rainbow trout liver tumors initiated by aflatoxin B1. 164 72


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