Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rectal biopsy specimens from control subjects, patients with either active or quiescent ulcerative colitis, and patients with Crohn's colitis were examined histologically and assayed for marker enzymes associated with tissue organelles. They were catalase (peroxisome); neutral alpha-glucosidase (endoplasmic reticulum); alkaline phosphatase (plasma membrane); malate dehydrogenase (mitochondria); lactate dehydrogenase (cytosol). There was no significant change in these enzyme activities in patient samples compared with controls. Activities of three acid hydrolases (lysosomal enzymes), beta-glucuronidase, acid phosphatase, and N-acetyl-beta-glucosaminidase, were also assayed in the biopsy samples. Decreased activities of all three enzymes were noted in ulcerative colitis, particularly in active disease. Normal values were obtained in Crohn's colitis. Measurement of lysosomal integrity by assays of latent N-acetyl-beta-glucosaminidase activity revealed similar results in control and colitic subjects. It is suggested that the lysosomal changes reflect a specific tissue release of enzyme and may be implicated in the pathogenesis of the tissue damage.
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PMID:Organelle pathology in ulcerative and Crohn's colitis with special reference to the lysosomal alterations. 671 88

Present knowledge of the in situ intracellular localization of acid hydrolases is mainly based on enzyme-cytochemical observations. In the preputial gland cells beta-glucuronidase and acid phosphatase were thus demonstrated in lysosome-like secretory granules and the GERL system. We applied immunocytochemistry to localize beta-glucuronidase at the earliest sites of biosynthesis. Lysosomal beta-glucuronidase was purified from preputial gland by column chromatography and SDS gel electrophoresis. Antibodies were raised in rabbit and affinity-purified preparations were used for immunocytochemistry on thin frozen sections of perfusion fixed preputial glands. Indirect procedures were applied with a second antibody labelled with rhodamine for fluorescence, and 5 or 8 nm protein A-gold probes for electron microscopy. beta-Glucuronidase occurred in all cells, except for the precursor cells, and was localized throughout the endoplasmic reticulum and perinuclear space, in all Golgi cisternae and storage granules, and in autophagic vacuoles. Thus in the preputial gland cell, beta-glucuronidase is present in both the lysosomal and the secretory system.
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PMID:Immunocytochemical localization of beta-glucuronidase in the male rat preputial gland. 674 3

The authors studied combined effect of aniline (20 mg/kg for a period of 4 weeks in drinking water) and nitrosodimethylamine (NDMA) (30 mg/kg, a single intragastric dose) on the activity of enzymes of different subcellular structures: endoplasmic reticulum (cytochromes P450, B5, acetylesterase), mitochondria (malate dehydrogenase) and the content of N-acetylneuraminic acid in rat liver and of lysosomes (beta-glucuronidase, beta-galactosidase). The combined action of NDMA and aniline was accompanied by more pronounced changes in the indices under investigation than isolated administration of the given chemical substances. The most pronounced aggravation of the unfavourable changes was observed in the activity of enzymes connected with the processes of oxidation and energy supply to the cell (malate dehydrogenase) and the metabolism of glucuronides (beta-glucuronidase) as well as in the content of N-acetylneuraminic acid. This may be connected with the modifying effect of aniline on the toxic effect of NDMA.
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PMID:Combined effect of nitrosodimethylamine and aniline on the enzyme systems of subcelluar structures. 680 54

The effects of indium-chloride (InCl3) on hepatocyte structure and function were studied in male rats injected with doses of 0, 10, 20, or 40 mg of InCl3/kg and killed after 16 hours. Fragmentation and degranulation of the rough endoplasmic reticulum and increased numbers of In- and Fe-containing autophagic lysosomes were the most marked cellular changes observed by electron microscopy. Morphometric analyses of hepatocytes disclosed a maximal 4-fold increase in the volume density of the lysosome compartment and a 2-fold decrease in the volume density of the vacuole compartment. Surface densities of the mitochondrial cristae and rough endoplasmic reticulum were increased by 1.5-fold, whereas the surface densities of the smooth endoplasmic reticulum showed a maximal increase of 7-fold. These structural changes were associated with inhibition of microsomal aniline hydroxylase by as much as 50% and ethoxyresorufin-O-deethylase by as much as 30% but no change in aminopyrine demethylase activity. Microsomal acid phosphatase activity was also decreased to 74% of control, whereas beta-glucuronidase was unchanged. Mild inhibition of mitochondrial respiratory function but no changes in marker enzyme activities were noted. Lysosomal marker enzyme activities were also unaffected, with the exception of acid phosphatase, which was maximally decreased to 55% of control. The data indicate that acute InCl3 injection produces a primary effect on hepatocyte endoplasmic reticulum structure with attendant changes in both heme- and nonheme-dependent biochemical functions. These findings suggest that altered regulation of hepatic microsomal heme metabolism by indium and other metals occurs as part of a general process involving degradative changes in the endoplasmic reticulum structure due to membrane damage with subsequent lysosomal autophagy of nonfunctional components.
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PMID:Alteration of hepatic microsomal structure and function by indium chloride. Ultrastructural, morphometric, and biochemical studies. 683 87

By in vitro translation of mRNA's isolated from free and membrane-bound polysomes, direct evidence was obtained for the synthesis of two lysosomal hydrolases, beta-glucuronidase of the rat preputial gland and cathespin D of mouse spleen, on polysomes bound to rough endoplasmic reticulum (ER) membranes. When the mRNA's for these two proteins were translated in the presence of microsomal membranes, the in vitro synthesized polypeptides were cotranslationally glycosylated and transferred into the microsomal lumen. Polypeptides synthesized in the absence of microsomal membranes were approximately 2,000 daltons larger than the respective unglycosylated microsomal polypeptides found after short times of labeling in cultured rat liver cells treated with tunicamycin. This strongly suggests that nascent chains of the lysosomal enzymes bear transient amino terminal signals which determine synthesis on bound polysomes and are removed during the cotranslational insertion of the polypeptides into the ER membranes. In the line of cultured rat liver cells used for this work, newly synthesized lysosomal hydrolases showed a dual destination; approximately 60 percent of the microsomal polypeptides detected after short times of labeling were subsequently processed proteolytically to lower molecular weight forms characteristic of the mature enzymes. The remainder was secreted from the cells without further proteolytic processing. As previously observed by other investigations in cultured fibroblasts (A. Gonzalez-Noriega, J.H. Grubbs, V. Talkad, and W.S. Sly, 1980, J Cell Biol. 85: 839-852; A. Hasilik and E.F. Neufeld, 1980, J. Biol. Chem., 255:4937-4945.) the lysosomotropic amine chloroquine prevented the proteolytic maturation of newly synthesized hydrolases and enhanced their section. In addition, unglycosylated hydrolases synthesized in cells treated with tunicamycin were exclusively exported from the cells without undergoing proteolytic processing. These results support the notions that modified sugar residues serve as sorting out signals which address the hydrolases to their lysosomal destination and that final proteolytic cleavage of hydrolase precursors take place within lysosome itself. Structural differences in the carbohydrate chains of intracellular and secreted precursors of cathespin D were detected from their differential sensitivity to digestion with endoglycosidases H and D. These observations suggest that the hydrolases exported into the medium follow the normal secretory route and that some of their oligosaccharides are subject to modifications known to affect many secretory glycoproteins during their passage through the Golgi apparatus.
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PMID:Biosynthesis of lysosomal hydrolases: their synthesis in bound polysomes and the role of co- and post-translational processing in determining their subcellular distribution. 706 51

The subcellular distribution of the NADPH oxidase of guinea-pig peritoneal-elicited macrophages was investigated. Post-nuclear supernatants obtained from PMA-stimulated macrophages were fractionated in discontinuous sucrose gradients. The NADPH oxidase was found to be enriched at the interface between 20 and 34 per cent sucrose. This interface was also enriched in 5'-nucleotidase, a plasma membrane marker and in glucose-6-phosphatase and NADPH-cytochrome c reductase, two endoplasmic reticulum markers. The distribution in the gradient of beta-glucuronidase, a marker of lysosomes and of succinate dehydrogenase, a marker of mitochondria was clearly different from that of NADPH oxidase and of the markers of plasma membrane and of endoplasmic reticulum. These results indicated that in stimulated-elicited macrophages the NADPH oxidase is associated with a membrane fraction. With the fractionation technique employed it was not possible to clarify whether the oxidase is located in the plasma membrane or in the endoplasmic reticulum. In order to clarify this matter the isolation of phagosomes was performed. NADPH oxidase was found to be enriched in the phagosomal fraction. Phagosomes were also found to be enriched in the plasma membrane marker 5'-nucleotidase. Glucose-6-phosphatase,, a marker of endoplasmic reticulum, and beta-glucuronidase, a marker of lysosomes were not enriched in the phagosomal fraction. The results obtained clearly suggest that the activated NADPH oxidase of peritoneal elicited macrophages of guinea pig is located in the plasma membrane.
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PMID:Plasma membrane and phagosome localisation of the activated NADPH oxidase in elicited peritoneal macrophages of the guinea-pig. 706 27

A gene complex consists of a structural gene with its associated regulatory information; together they behave as the functional and evolutionary unit of mammalian chromosomes. The use of congenic lines, in which alternate forms, or haplotypes, of a gene complex are transferred into a common genetic background by repeated backcrossing, provides a means of comparing the regulatory properties of different haplotypes of a gene complex without the complications introduced by extraneous genetic differences. We have now carried out such a study of the A, B, and H haplotypes of the beta-glucuronidase gene complex, [Gus], in mice. These haplotypes were derived from strains A/J, C57BL/6J, and C3H/HeJ and were compared against the C57BL/6J genetic background. Enzyme structure was compared in terms of charge (isoelectric point), stability (rate of thermal denaturation), substrate affinity (for 4 MU glucuronide), and antigenicity (reactivity with a standard antibody). Compared to the B form, the enzyme coded by the A haplotype has a lower isoelectric point, and that coded by the H haplotype is less stable. The decreased stability is the result of a lower activation energy for the thermal denaturation reaction. These differences were maintained in the congenic strains. All three enzyme forms showed identical substrate affinities. Antigenicity per enzyme unit was also identical for all three, indicating that none lacks an antigenic site possessed by the others and that they all possess the same catalytic activity per molecule. The expression of alleles of the Gus-t temporal locus within the gene complex was not affected by transfer into the C57BL/6 genetic background. The same developmental switches in enzyme activity were seen in each case. Transfer into the C57Bl/6 background also did not affect expression of the Gus-r regulator determining androgen inducibility of beta-glucuronidase synthesis in kidney epithelial cells. However, enzyme accumulation in induced cells was altered when the haplotypes were transferred into the C57BL/6 genetic background. Since the rate of synthesis was not affected, it suggests that the genetic differences between strains that are not linked to the [Gus] complex affect the rate of enzyme loss by degradation or secretion. Beta-Glucuronidase in liver is present in both lysosomes and endoplasmic reticulum (microsomes). The relative amount of enzyme at each site depended on both the indentity of the structural allele and the function of unlinked genetic modifiers. Within the C57BL/6 background the percentage of total enzyme present in the microsome fraction was the order A greater than B greater than H. For the H form of the enzyme the percentage was appreciably greater in the C3H genetic background compared to C57BL/6. As expected, then, the [Gus] complex contains all of the genetic determinants of enzyme structure detected by thermal stability and isoelectric point measurements...
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PMID:Expression of beta-glucuronidase haplotypes in prototype and congenic mouse strains. 711 85

Present experiment was aimed to study whether 16, 16' dimethylprostaglandin E2 (dmPGE2), Hepatofalk (HF), or Orotofalk (OF) may prevent an acute liver damage induced in rats with D-galactosamine (GalN). Fifty male rats were divided into 5 groups: 1. controls, 2. rats receiving GalN 750 mg/kg b. w. intraperitoneally, 3. animals pretreated with 5 microgram/kg dmPGE2 given subcutaneously 24 hours prior to, 30 min prior to and 6 hours after GalN. Rats of group 4 received HF 0,8 ml/kg intramuscularly and group 5 OF 0,3 caps/kg intragastrically 24 hours prior to, 30 min prior to and 6 hours after GalN. Animals were sacrificed 24 hours after GalN injection. Histological, histochemical and ultrastructural studies of the liver were performed. In rats receiving GalN alone (group 2) typical severe liver damage consisting of acidophilic necrosis of hepatocytes, periportal and intralobular inflammatory infiltration, hypertrophy and hyperplasia of Browicz-Kupffer cells has been observed. Histochemical investigations showed in this group fatty degeneration and a decrease in glycogen content in hepatocytes, irregular distribution of lysosomes, numerous cytolysosomes and uneven decrease in lysosomal enzymes activity (acid phosphatase and beta-glucuronidase). Ultrastructural studies revealed depletion in glycogen, fat droplets, hypertrophy of smooth endoplasmic reticulum and numerous autophagic vacuoles. Some of these vacuoles or residual bodies were dropping out into intercellular space. Focal accumulation of lamellar cytomembranes as well as condensation of heterochromatin in nuclei were also observed. Pretreatment of animals with dmPGE2 (group 3), HF (group 4) or OF (group 5) prior to GalN prevented liver cell necrosis. Histological, histochemical and ultrastructural picture of the liver was in these groups close to normal. Only very slight hypertrophy and hyperplasia of Browicz-Kupffer cells, was seen as well as depletion of glycogen and hypertrophy of smooth endoplasmic reticulum in hepatocytes. We conclude dmPGE2, HF and OF offered impressive cytoprotection against GalN induced liver damage in rat.
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PMID:Cytoprotective effect of 16, 16' dimethyl prostaglandin E2 and some drugs on an acute galactosamine induced liver damage in rat. 720 70

Prolactin proteolysis by rat pituitary homogenates was assayed by measuring the release of trichloroacetic acid-soluble peptides from 125I-labelled rat prolactin. There was a distinct optimum at pH 4.3, with only trace amounts of activity at neutral and alkaline pH. Rat pituitary homogenates were subjected to analytical subcellular fractionation by sucrose density gradient centrifugation in a Beaufay automatic zonal rotor. The principal organelles were characterized by their respective marker enzymes, including: cytosol (lactate dehydrogenase); plasma membrane (5'-nucleotidase); lysosomes (N-acetyl-beta-glucosaminidase, beta-glucuronidase); mitochondria (particulate malate dehydrogenase); endoplasmic reticulum (neutral alpha-glucosidase); prolactin granules (radioimmunoassayable prolactin). Acid prolactin protease had a similar distribution to the lysosomal marker enzymes. A localisation of the activity to lysosomes was confirmed by subcellular fractionation experiments in which the lysosomes were selectively disrupted with low concentrations of the membrane perturbant, digitonin. Experiments with specific inhibitors of the lysosomal cathepsins indicate that both cathepsins B and D are implicated in pituitary prolactin proteolysis.
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PMID:Analytical subcellular fractionation of rat pituitary homogenates, with special reference to prolactin proteolysis by lysosomes. 729 6

This is the history of discoveries of several enzyme tumor markers in the awardees laboratory. The first, beta-glucuronidase, was originally related to the physiological actions of estrogens and androgens. Perfection of histochemical techniques based on new substrates demonstrated the dual localization of beta-glucuronidase in endoplasmic reticulum and lysosomes. Tumor tissues, in general, are enriched with beta-glucuronidase. Next, acid phosphatase of the prostate gland possesses the distinctive property of undergoing inhibition by L-tartrate. This organ-specific inhibitor was incorporated into the Fishman-Lerner method for measuring serum acid phosphatase of prostatic origin. This significantly increased the specificity of the measurement of serum acid phosphatase for prostatic cancer. Finally, the discovery of the Regan Isoenzyme, placental alkaline phosphatase (PLAP) in a patient with disseminated lung cancer provided a tumor marker useful in the management of gonadal tumors, in particular. Closely related to PLAP is germ cell alkaline phosphatase which is eutopically expressed in seminoma. Finally, radioimmunolocalization and radioimmunotherapy of PLAP in these tumors have been achieved by others.
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PMID:The 1993 ISOBM Abbott Award Lecture. Isozymes, tumor markers and oncodevelopmental biology. 756 86


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