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)

The clinically relevant morphological changes of the skin during aging can be summarized by the term "senile atrophy". The changes are a diminished thickness of epidermis with a reduced mitosis rate of epidermal basal cells, shortened and attenuated rete ridges, reduction of epidermal appendages, and a decreased number of fibroblasts and capillaries in the dermis. Corresponding to these morphological findings regarding the cell number in the senile skin (cutis) we found a slight decrease in the DNA concentration of human and rat cutis. The specific DNA activity (3H-thymidine incorporation rate related to DNA concentration) decreased in presenile versus adult animals. The mesenchymal changes in the dermis have been morphologically described by the term "senile elastosis" or "elastoid collagen degeneration", but in fact they correspond to a progressive collagen denaturation with aging. The total collagen concentration, here determined as the hydroxyproline concentration in the human cutis, shows almost constant values from the 3rd until the 9th decade of life in both sexes. This is also true for the skin of two different rat strains. The insoluble collagen fraction shows a relative increase to the disadvantage of the soluble collagen fractions, which can be interpreted as an indicator of a decelerated collagen turnover. In spite of the decelerated turnover, i.e. a prolonged half-life of the collagen metabolism in the skin, the indicators of the collagen neosynthesis (14C-proline incorporation rate, specific hydroxyproline activity, prolyl-hydroxylase activity) are significantly elevated in the cutis of presenile versus adult rats. Any connection of these findings with a possible change in the distribution of collagen types in the senile skin (e.g. pericapillar fibrosis with increase of collagen type I as well as changes in the distribution of type I, III, IV and V) can only be discussed at present. The glycosaminoglycans in the cutis show a minimal increase of the total content of hexosamines and uronic acids with a significant shift in the ratio of the glycosaminoglycan components in favour of dermatan sulfate and keratan sulfate and to the disadvantage of hyaluronic acid and partly also of chondroitin-4-sulfate and -6-sulfate. The neosynthesis of sulfated glycosaminoglycans (indicator method: 35S-sulfate incorporation rate) is only slightly increased whereas the enzyme activities being specific for the glycosaminoglycan catabolism (beta-glucuronidase, beta-N-acetyl-glucosaminidase) are significantly decreased with aging of the skin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Skin changes in advanced age--biochemical findings corresponding to morphology?]. 376 76

Heparan sulfate (HS), a prominent component of vascular endothelial basal lamina, is cleaved into large Mr fragments and solubilized from subendothelial basal lamina-like matrix by metastatic murine B16 melanoma cells. We have examined the degradation products of HS and other purified glycosaminoglycans produced by B16 cells. Glycosaminoglycans 3H-labeled at their reducing termini or metabolically labeled with [35S]sulfate were incubated with B16 cell extracts in the absence or presence of D-saccharic acid 1,4-lactone, a potent exo-beta-glucuronidase inhibitor, and glycosaminoglycan fragments were analyzed by high speed gel permeation chromatography. HS isolated from bovine lung, Engelbreth-Holm-Swarm sarcoma, and subendothelial matrix were degraded into fragments of characteristic Mr, in contrast to hyaluronic acid, chondroitin 6-sulfate, chondroitin 4-sulfate, dermatan sulfate, keratan sulfate, and heparin which were essentially undegraded. Heparin, but not other glycosaminoglycans, inhibited HS degradation. The time dependence of HS degradation into particular Mr fragments indicated that HS was cleaved at specific intrachain sites. In order to determine specific HS cleavage points, HS prereduced with NaBH4 was incubated with a B16 cell extract and HS fragments were separated. The newly formed reducing termini of HS fragments were then reduced with NaB[3H]4, and the fragments hydrolyzed to monosaccharides by trifluoroacetic acid treatment and nitrous acid deamination. Since 3H-reduced terminal monosaccharides from HS fragments were overwhelmingly (greater than 90%) L-gulonic acid, the HS-degrading enzyme responsible is an endoglucuronidase (heparanase).
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PMID:Metastatic melanoma cell heparanase. Characterization of heparan sulfate degradation fragments produced by B16 melanoma endoglucuronidase. 669 65

We previously described a diverse family of sulfated anionic N-linked oligosaccharides released by peptide: N-glycosidase F (PNGaseF) from calf pulmonary artery endothelial (CPAE) cells (Roux, L., Holoyda, S., Sundblad, G., Freeze, H.H., and Varki, A. (1988) J. Biol. Chem. 263, 8879-8889). Since a major fraction of the intact lung consists of endothelial cells, we reasoned that bovine lung might be a rich source of similar molecules. Total N-linked oligosaccharides from bovine lung acetone powder were released by PNGaseF, labeled by [3H]NaBH4 reduction, and the anionic fractions were studied with a variety of techniques. The sugar chains with lesser negative charge (designated Class I) share several properties of conventional multiantennary complex-type chains. However, unlike the case with CPAE cells, sialic acids account only for a minority of the anionic properties and only a small proportion carry sulfate esters. A variety of different treatments indicate that most of the unexplained negative charge is due to multiple carboxylic acid groups. Resistance to beta-glucuronidase and alpha-iduronidase suggests that these may be previously undescribed modifications of mammalian oligosaccharides. The most highly charged N-linked chains (designated Class II) are more similar in general structure to the corresponding ones from CPAE cells, although relatively more abundant. Their high charge is primarily due to chondroitin sulfate, heparin/heparan sulfate, or keratan sulfate glycosaminoglycan chains. Sequential digestion studies suggest that a significant proportion of these molecules have more than one type of glycosaminoglycan chain associated with them. Compositional analysis indicates the presence of xylose residues in Class II, but not Class I molecules. However, unlike the case with conventional glycosaminoglycans, these residues are not at the reducing terminus. Most previously reported structures of complex-type N-linked oligosaccharides are derived from the glycoproteins of blood cells, plasma, or the secretions of cultured mammalian cells. This library of N-linked oligosaccharides from an intact mammalian organ (lung) contains a high proportion of novel anionic sugar chains whose structures are different from conventional complex-type sialylated chains and only partially related to those from CPAE cells. Further exploration of the N-linked chains of intact mammalian tissues seems warranted.
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PMID:Unusual anionic N-linked oligosaccharides from bovine lung. 749 28