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

A brief illustrated account is presented of the light microscopic pathology, histochemistry of lysosomal enzymes, and fine structural changes in the nerves of patients with untreated or treated lepromatous leprosy. Predominant bacillation of the Schwann cells of unmyelinated fibres, degeneration of their axons, prominence of phagolysosomes, and disappearance of these cells with endoneurial collagenosis were observed on electronmicroscopic examination of the index branch of the radial cutaneous nerve. Although there were changes in the blood vessels and proliferation of perineurium, bacillation of endothelial or perineurial cells was much less conspicuous. Intact and degenerating forms of M. leprae were found in both treated and untreated patients, fragmenting or crumpled forms being more frequent in the treated. Both groups of patients also showed increased lysosomal enzyme activity, evidenced by single or paired paranodal spots of acid phosphatase and beta-glucuronidase in Schwann cells in histochemical preparations of the nerve. There was lesser activity, and activity in fewer cells, in the case of beta-glucuronidase than of acid phosphatase. Diffuse beta-glucuronidase activity was found in the wall of empty-looking oval chambers in the Schwann cells, and acid-fast bacilli were seen in these chambers. In teased fibre preparations, both axonal degeneration and segmental demyelination were found. In semi-thin araldite sections, the myelinated fibre density was either preserved or reduced; large diameter fibres were more frequently depleted, with tall peaks of smaller fibres seen on plotting diameter spectra.
 ...
PMID:Lepromatous leprosy as a model of Schwann cell pathology and lysosomal activity. 39 8

Neurotoxic effects of the combined exposure of rats to carbon disulphide (CS2) and ethanol (EtOH) were studied. Biochemical and ultrastructural evaluation of the central nervous system (CNS) and peripheral nervous system (PNS) was performed. Male Wistar rats were exposed to CS2 vapour (0.8 mg/l air) and to 10% alcohol in the drinking water for 8 months. EtOH elevated the increase in beta-glucuronidase activity caused by CS2 in the hippocampus and in the cerebral cortex. No effect on the high-affinity synaptosomal uptake of L-glutamate and GABA was observed and no marked ultrastructural changes in the tested brain regions were found. In the peripheral nerves CS2 alone evoked axonal degeneration whereas CS2 combined with EtOH caused disturbances in myelin. Ultrastructural changes preceded biochemical alterations in the PNS and the biochemical indicators of peripheral neuropathy such as beta-glucuronidase activity and cholesterol ester content were not significantly affected. It is suggested that CS2 and EtOH combined affect both PNS and CNS to a higher extent than each of these substances alone.
 ...
PMID:Neurotoxic effects of the combined exposure to carbon disulphide and ethanol in rats. 373 35

Four enzymes related to specific cell functions were assayed in rat sciatic nerve injury by crush (cr) or crush and ligation (cr-lig) after 2, 7, and 15 days in situ. Enzyme activities in segments of sciatic nerve proximal and distal to the injury were compared to those in corresponding segments of the contralateral nerve. Choline acetyltransferase (CAT) activity in the distal portion decreased by 65% for cr and almost to zero for cr-lig by day 7, while in the proximal portions CAT decreased to 70% of control values by 7 days and to 50% at 15 days after cr-lig. The activity of the Schwann cell-myelin-associated enzyme 2',3'-cyclic nucleotide phosphohydrolase (CNP) decreased slowly distal to the injury. Distal to both types of injury the lysosomal enzyme beta-glucuronidase (GLR) increased six- to eightfold by 15 days. Proximal to injury GLR also increased (P cr X 2.5, P cr-lig X 5) but the peak proximally was attained by day 7. Despite interruption of axonally transported enzymes, the activities of the metabolic enzyme creatine kinase (CK) increased distal to injury apparently reflecting changes in the functions of the Schwann cells. The loss of metabolic enzymes from the axonal compartment may be completely obscured by reciprocal changes in the non-neuronal compartments if the activity is present in both compartments.
 ...
PMID:Enzyme changes in axon, myelin, and Schwann cells in injured sciatic nerve. 631 Jan 39

The neurological effects of four synthetic pyrethroids resmethrin, permethrin, cypermethrin, and deltamethrin have been investigated in the rat to establish whether there is a correlation between the clinical-functional status of the animal and peripheral nerve damage as measured biochemically. Neuromuscular dysfunction was assessed by means of the inclined plane test and peripheral nerve damage by reference to beta-glucuronidase and beta-galactosidase activity increases in nerve tissue homogenates from treated and control animals. A transient functional impairment was found in animals treated with any one of the four pyrethroids tested and in all cases this was maximal at the end of the 7 day subacute dosing regimen. Significant increases in beta-glucuronidase and beta-galactosidase were found 3-4 weeks after the start of dosing in the distal portion of the sciatic/posterior tibial nerves from permethrin, cypermethrin, and deltamethrin treated animal; but no changes were found in remesthrin-dosed animals. It is concluded therefore, that there is no direct correlation between the time-course of the neuromuscular dysfunction and the neurobiochemical changes. This suggests that these pyrethroids have at least two distinct actions--a short-term pharmacological effect and at near-lethal dose levels a more chronic neurotoxic effect that results in sparse axonal nerve damage.
 ...
PMID:Intoxication with four synthetic pyrethroids fails to show any correlation between neuromuscular dysfunction and neurobiochemical abnormalities in rats. 631 30

The enzymes beta-glucuronidase and acid phosphatase have been assayed by histochemical and by fluorimetric methods above and below a tightly tied ligature on the rat sciatic nerve over the subsequent 10 days. These findings have been compared with similarly treated animals also given four daily doses of acrylamide (50 mg/kg). The following have been found: 1 during this time, acrylamide at this dose causes slight increases in beta-glucuronidase in untied sciatic nerves, detectable both histochemically and fluorimetrically; 2 below the ligature both enzyme activities were greatly increased and this was slightly reduced in the acrylamide-dosed animals; 3 there was a mild rise in beta-glucuronidase activity in the 1.0 cm above the ligature in undosed animals demonstrable both histochemically and fluorimetrically; 4 that in the acrylamide-dosed animals there was a marked rise in beta-glucuronidase activity both 1.0 cm and 2.0 cm above the ligature which was intensified at 7 days and at 10 days after dosing. This was demonstrated both histochemically and fluorimetrically. These results are discussed in the light of the known sheath cell and axonal responses to acrylamide intoxication.
 ...
PMID:The effects of acrylamide on beta-glucuronidase and acid phosphatase activities in rat sciatic nerve above and below a ligature. 716 59

A portion of the lysosomal enzymes produced by cells is secreted, diffuses through extracellular spaces, and can be taken up by distal cells via mannose-6-phosphate receptor-mediated endocytosis. This provides the basis for treating lysosomal storage diseases, many of which affect the CNS. Normal enzyme secreted from a cluster of genetically corrected cells has been shown to reverse storage lesions in a zone of surrounding brain tissue in mouse disease models. However, low levels of enzyme activity and reduction of storage lesions also have been observed at sites in the brain that may not be explained by a contiguous gradient of secreted enzyme diffusing away from the genetically corrected cells. No direct evidence for alternative mechanisms of enzyme transport has been shown, and little is understood about the intracellular movement of lysosomal enzymes in neurons. We investigated whether axonal transport could occur, by expressing an eukaryotic lysosomal enzyme that can be visualized in tissue sections (beta-glucuronidase) in brain structures that have defined axonal connections to other structures. This resulted in the transfer of enzyme to, and a reversal of storage lesions in, neurons that project to the gene expression site, but not in nearby structures that would have been corrected if the effect had been mediated by diffusion. In addition, transduction of cells in the subventricular zone resulted in the uptake of beta-glucuronidase by cells entering the rostral migratory stream. Gene transfer to specific neuronal circuits or cells in migratory pathways may facilitate delivery to the global brain lesions found in these disorders.
 ...
PMID:Distribution of a lysosomal enzyme in the adult brain by axonal transport and by cells of the rostral migratory stream. 1215 23

Previous reports suggest that age-related lysosomal disturbances contribute to Alzheimer-type accumulations of protein species, blockage of axonal/dendritic transport, and synaptic decline. Here, we tested the hypothesis that lysosomal enzymes are upregulated as a compensatory response to pathogenic protein accumulation. In the hippocampal slice model, tau deposits and amyloidogenic fragments induced by the lysosomal inhibitor chloroquine were accompanied by disrupted microtubule integrity and by corresponding declines in postsynaptic glutamate receptors and the presynaptic marker synaptophysin. In the same slices, cathepsins B, D, and L, beta-glucuronidase, and elastase were upregulated by 70% to 135%. To address whether this selective activation of the lysosomal system represents compensatory signaling, N-Cbz-L-phenylalanyl-L-alanyl-diazomethylketone (PADK) was used to enhance the lysosome response, generating 4- to 8-fold increases in lysosomal enzymes. PADK-mediated lysosomal modulation was stable for weeks while synaptic components remained normal. When PADK and chloroquine were co-infused, chloroquine no longer increased cellular tau levels. To assess pre-existing pathology, chloroquine was applied for 6 days after which its removal resulted in continued degeneration. In contrast, enhancing lysosomal activation by replacing chloroquine after 6 days with PADK led to clearance of accumulated protein species and restored microtubule integrity. Transport processes lost during chloroquine exposure were consequently re-established, resulting in marked recovery of synaptic components. These data indicate that compensatory activation of lysosomes follows protein accumulation events, and that lysosomal modulation represents a novel approach for treating Alzheimer disease and other protein deposition diseases.
 ...
PMID:Lysosomal activation is a compensatory response against protein accumulation and associated synaptopathogenesis--an approach for slowing Alzheimer disease? 1276 85

We have inoculated a herpes simplex virus type 1 (HSV-1) vector into a variety of sites in the mouse brain and assayed the regions of latency and expression of a beta-glucuronidase (GUSB) cDNA from the latency-associated transcript promoter. Injection sites used were somatosensory cortex, visual cortex, striatum, dorsal hippocampus, and CSF spaces. Latent vector was detected in regions at a distance from the respective injection sites, consistent with axonal transport of vector. Regions of GUSB activity varied by injection site and included cerebral cortex, striatum, thalamus, hypothalamus, substantia nigra, hippocampus, midbrain, pons, medulla, cerebellum, and spinal cord. After a single injection, GUSB enzymatic activity reached wild-type levels in several brain regions. GUSB was found in some areas without any detectable vector, indicative of axonal transport of GUSB enzyme. GUSB-deficient mice, which have the lysosomal storage disease mucopolysaccharidosis (MPS) VII, have lysosomal storage lesions in cells throughout the brain. Adult MPS VII mice treated by injection of vector into a single site on each side of the brain had correction of storage lesions in a large volume of brain. The potential for long-term, widespread correction of lysosomal storage diseases with HSV-1 vectors is discussed.
 ...
PMID:Widespread correction of lysosomal storage in the mucopolysaccharidosis type VII mouse brain with a herpes simplex virus type 1 vector expressing beta-glucuronidase. 1651 90