Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.23.5 (cathepsin D)
4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The levels of six lysosomal enzymes (acid phosphatase, beta-acetylglucosaminidase, cathepsin D, beta-galactosidase, arylsulfatase A, and beta-glucuronidase) and four neutral and alkaline hydrolases (esterase, inorganic phyrophosphatase, alkaline phosphatase, and 5'-nucleotidase) were measured in osteoarthritic, rheumatoid and control synovia. All enzyme levels in diseased synovium except esterase values in osteoarthritis were significantly elevated compared with controls. The mean values of the group of acid hydrolases and the group of neutral and alkaline hydrolases in osteoarthritic synovia were 1.9- and 2.0-fold greater than those of control specimens. In rheumatoid synovia, the values were 4.2- and 4.5 fold greater than control for the same enzymes. Levels in rheumatoid synovia were significantly higher than those in osteoarthritic synovia with the exception of 5'-nucleotidase. Only a limited correlation between the extents of inflammation present in the synovia and the levels of a lysosomal marker enzyme (cathepsin D) was observed. These results demonstrate that whatever the mechanism, increased levels of acid hydrolases as well as certain neutral and alkaline hydrolases are present in osteoarthritic and rheumatoid synovia, and these enzymes are probably contained in the synovial lining cells.
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PMID:Acid, neutral, and alkaline hydrolases in arthritic synovium. 0 9

The enzymatic activity of five acid hydrolases: acid phosphatase, arylsulfatase A, deoxyribonuclease, beta-glucuronidase, and cathepsin D, was assayed in fetal (fifteenth and eighteenth days of pregnancy) and neonatal (Days 0, 5, 10, and 15 post-partum) mouse liver. With the exception of cathepsin D, the activity increased around birth to levels varying according to the enzyme. Histochemical observations of other authors appear to justify, at least in part, the present results, which indicate that late days of fetal development and early neonatal life may constitute a transitional stage to full lysosomal enzyme functionality of the adult organ. The livers of the mothers were also assayed for the same enzymes. Each activity showed a peculiar pattern which was, in turn, different from that found in the liver of the litter for the same enzyme, probably as a cause of the metabolic requirement of the gland. The hypothesis that the lysosomes are heterogeneous in their enzyme composition is suggested by the variety of enzymatic patterns found in the liver of the litters and their mothers.
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PMID:The development of lysosomal apparatus. I. Lysosomal enzyme activities in the liver of mice at perinatal stages and those of their mothers. 2 3

Patients with the DMC syndrome have been suggested to possess a specific sulfatase abnormality and/or to be deficient in a proteinase cleaving glycoprotein-acid mucopolysaccharide (AMP) linkage. We have previously found in DMC patients an abnormal excretion of urinary AMPs of which hyaluronic acid and chondroitin sulfate (A + C) were oversulfated and keratosulfate and heparan sulfate were undersulfated. Lysosomal acid proteinase, i.e. cathepsin D (EC 3.4.23.5) and neutral proteinase : elastase (EC 3.4.21.11) and cathepsin G were found to be normal in DMC patients. However, alpha 2-macroglobulin in serum was raised. This increase may be associated with a complex formation of alpha 2-macroglobulin with a neutral proteinase released from the cells. Increased levels of chondroitin sulfate N-acetylgalactosamine-6-sulfate sulfatase and sulfamidase and decreased enzymic levels of arylsulfatase A and B (EC 3.1.6.1) were found in leucocytes of DMC patients. The sulfatase activities assayed in the present study support our theory that a specific sulfatase abnormality may exist in the DMC syndrome.
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PMID:Lysosomal (leucocyte) proteinase and sulfatase levels in Dyggve-Melchior-Clausen (DMC) syndrome. 7 86

Diphosphonates are known to inhibit bone resorption in tissue culture and in experimental animals. This effect may be due to their ability to inhibit the dissolution of hydroxyapatite crystals, but other mechanisms may be important. Since lysosomal enzymes have implicated in the process of bone resorption, we have examined the effect of several phosphonates and of a polyphosphate (P20,2) on lysosomal hydrolases derived from rat liver and rat bone. Dichloromethylene diphosphonate strongly inhibited acid beta-glycerophosphatase (EC 3.1.3.2) and acid p-nitrophenyl phosphatase (EC 3.1.3.2) and to a lesser degree (in descending order) acid pyrophosphatase (EC 3.1.3.-), arylsulfatase A (EC 3.1.6.1), deoxyribonuclease II(EC 3.1.4.6) and phosphoprotein phosphatase (EC 3.1.3.16) of rat liver. Inhibition of acid p-nitrophenyl phosphatase and arylsulfatase A was competitive. Ethane-1-hydroxy-1, 1-diphosphonate did not inhibit any of these enzymes, except at high concentrations. Neither dichloromethylene diphosphonate nor ethane-1-hydroxy-1, 1-diphosphonate had any effect on beta-glucuronidase (EC 3.2.1.31), arylesterase (EC 3.1.1.2) and cathepsin D (EC 3.4.23.5). Of several other phosphonates tested only undec-10-ene-1-hydroxy-1, 1-diphosphonic acid inhibited acid p-nitrophenyl phosphatase strongly, the polyphosphate (P20, I) had little effect. Acid p-nitrophenyl phosphatase in rat calvaria extract behaved in the same way as the liver enzyme and was also strongly inhibited by dichloromethylene diphosphonate, but not by ethane-1-hydroxy-1, 1-diphosphonate. It is suggested that the inhibition of bone resorption by dichloromethylene diphosphonate might be due in part to a direct effect of this diphosphonate on lysosomal hydrolases.
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PMID:The effect of several diphosphonates on acid phosphohydrolases and other lysosomal enzymes. 17 70

In addition to their general function in cellular homeostasis, thyroid lysosomes play an essential role in the biosynthesis of thyroid hormones by cleaving the macromolecular prohormone, thyroglobulin. In the present work, we have attempted to determine whether the enzyme composition of thyroid lysosomes differs from that of lysosomes from other tissues. Lysosomal enzymes, cathepsin D, beta-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase, alpha-L-fucosidase, hexosaminidase, and arylsulfatase A and B, were assayed in crude fractions from various pig tissues, heart, brain, liver, kidney, thyroid, adrenals, ovary, and spleen. It appeared that the specific activity of arylsulfatase A was at least 20 times higher in the thyroid than in most other tissues. Thyroid lysosomes purified by isopycnic centrifugation on Percoll gradients contained two major polypeptides with apparent molecular weights of 58,000 and 54,000 representing about 30% of the total protein. These polypeptides were glycosylated and were exclusively found in the intralysosomal soluble fraction obtained by osmotic pressure-dependent lysis. By fractionating intralysosomal soluble proteins by velocity sedimentation on sucrose gradients or gel permeation chromatography we identified a thyroid arylsulfatase A holoenzyme which corresponds to a 120,000 Mr species. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses of the gradient or column fractions showed that the 120-kDa protein peak with arylsulfatase A activity essentially contained the 58- and 54-kDa polypeptides in equivalent amounts. In conclusion, arylsulfatase A, a heterodimer of 120 kDa composed of two nonidentical subunits, is the major protein component of thyroid lysosomes. The superabundance of this protein in purified thyroid lysosomes is related to the very high specific activity of the enzyme in the thyroid as compared to other tissues.
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PMID:Evidence for the presence of a very high concentration of arylsulfatase A in the pig thyroid: identification of arylsulfatase A subunits as the two major glycoproteins in purified thyroid lysosomes. 256 93

Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3-6 days afterward) the activity of beta-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of beta-N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not correlate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types.
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PMID:Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats. 287 99

This study tested the effects of different iodine intakes on thyroid ultrastructure and function in thyroid remnants after subtotal thyroidectomy (sub-tx). Removal of most of the thyroid gland causes an elevation of endogenous TSH, which chronically stimulates the residual tissue. Male Sprague-Dawley rats were divided into three groups; Low Iodine Group (LIG), Moderate Iodine Group (MIG), and High Iodine Group (HIG). There was no significant difference among total thyroid weights removed by sub-tx, but thyroid remnant weights and TSH levels were higher at death (6 weeks after sub-tx) in LIG than in MIG and HIG. Total specific activities of cathepsin D and of arylsulfatase A in the sedimentable and nonsedimentable subcellular fractions were at least 38% lower in LIG than in MIG and HIG. The ratio between relative follicular volume and colloid volume determined by morphometry was higher in LIG than in MIG and lower in HIG than in MIG. Ultrastructurally, the relative volume occupied by secondary lysosomes was higher in HIG than in MIG, whereas the number of secondary lysosomes was not higher in LIG than in controls. Autoradiographic studies with 125I revealed that a large part of the radioactivity was in thyroid cell secondary lysosomes in MIG and HIG when radioiodine was injected 3 weeks before death. It is concluded that after sub-tx, iodine 1) regulates the weight of thyroid remnants, perhaps only indirectly through TSH, 2) modulates the number of secondary lysosomes in thyroid cells, and 3) slows down the turnover of secondary lysosomes. An iodine-deficient regimen impedes the secondary lysosomes to increase. Because of these findings, we postulate that chronic TSH stimulation along with a possible toxic role of iodine after sub-tx could induce an accumulation of lysosomal bodies.
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PMID:Effects of iodine intake on thyroid secondary lysosomes after subtotal thyroidectomy. 338 83

The incorporation of [3H]leucine and [32P]phosphate into three lysosomal enzymes, cathepsin D, beta-hexosaminidase and arylsulfatase A by fibroblasts from six patients affected with mucolipidosis III was determined. In the mutant cells the incorporation of 32P in the enzymes was reduced by 70-97% as compared to controls. The residual phosphorylation of lysosomal enzymes is definitely higher than in fibroblasts from patients with mucolipidosis II, where apparently non-phosphorylated enzymes are formed. In mucolipidosis III the major part of the newly formed enzymes accumulated extracellularly and the cellular enzymes were recovered mainly in their processed forms. In mucolipidosis III arylsulfatase A and the processed forms of cathepsin D exhibited a heterogeneity that was not observed in controls. beta-Hexosaminidase and cathepsin D secreted by mucolipidosis III fibroblasts contained only a small amount of phosphorylated oligosaccharides with either one or two phosphate groups per oligosaccharide. As in controls the major fraction of phosphate was present as acid-labile phosphodiester resistant to alkaline phosphatase. The residual phosphorylation of lysosomal enzymes may be related to the partial intracellular retention and processing of these enzymes in fibroblasts from patients with mucolipidosis III.
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PMID:Impaired phosphorylation of lysosomal enzymes in fibroblasts of patients with mucolipidosis III. 612 Aug 34

Multiple sulfatase deficiency (mucosulfatidosis) is a lysosomal storage disorder characterized by the decrease in activities of all known sulfatases. To measure the apparent rate of synthesis and the half-life of arylsulfatase A in multiple sulfatase deficiency, fibroblasts from patients with the disease and from controls were subjected to pulse-chase labelling with radioactive amino acids. Arylsulfatase A and cathepsin D, a lysosomal enzyme that is not affected in multiple sulfatase deficiency, were isolated from cells and media by immunoprecipitation. The labelled polypeptides were separated by polyacrylamide gel electrophoresis, visualized by fluorography and quantified by liquid scintillation counting. Using single and double isotope techniques it was found that, as compared to cathepsin D, the apparent rate of synthesis of arylsulfatase A was 2--5 times lower and the half-life 4--9-times shorter in multiple sulfatase deficiency than in control fibroblasts. In multiple sulfatase deficiency fibroblasts the rates of endocytosis and the stabilities of endocytosed arylsulfatases A isolated from human urine and bovine tests were equal to those in metachromatic leucodystrophy fibroblasts. We postulate that in normal cells a gene product exists that affects the stability of sulfatases and that multiple sulfatase deficiency is due to a mutation in this gene.
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PMID:Enhanced breakdown of arylsulfatase A in multiple sulfatase deficiency. 612 72

Mannose 6-phosphate (Man-6-P) is a posttranslational carbohydrate modification typical of newly synthesized acid hydrolases that signals targeting from the Golgi apparatus to the lysosome via Man-6-P receptors (MPRs). Using iodinated cation independent MPR as a probe in a Western blot assay, we surveyed levels of Man-6-P glycoproteins in a number of different rat tissues. Considerable variation was observed with respect to total amounts and types of Man-6-P glycoproteins in the different tissues. Brain contained 2-8-fold more Man-6-P glycoproteins than other tissues, with relative abundance being brain >> testis approximately heart > lung approximately kidney approximately ovary approximately spleen > skeletal muscle approximately liver approximately serum. Analysis of 16 different lysosomal enzyme activities revealed that brain contains lower activities than other tissues which suggested that decreased removal of Man-6-P results in increased levels of Man-6-P glycoproteins. This was directly demonstrated by comparing activities of phosphorylated lysosomal enzymes, purified by immobilized MPR affinity chromatography, with total activities. The phosphorylated forms accounted for a considerable proportion of the MPR-targeted activities measured in brain (on average, 36.2%) but very little in lung, kidney, and liver (on average, 5.5, 2.3, and 0. 7%, respectively). Man-6-P glycoproteins were also isolated from rat brain by MPR affinity chromatography on a preparative scale. Of the 18 bands resolvable by SDS-polyacrylamide gel electrophoresis, seven bands were NH2-terminally sequenced and identified as the known lysosomal enzymes cathepsin L, cathepsin A, cathepsin D, alpha-galactosidase A, arylsulfatase A, and alpha-iduronidase. One of the major Man-6-P glycoproteins was identified as palmitoyl protein thioesterase, which was not previously thought to be lysosomal. This finding raises important questions about the cellular location and function of palmitoyl protein thioesterase, mutations in which result in the neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis.
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PMID:Rat brain contains high levels of mannose-6-phosphorylated glycoproteins including lysosomal enzymes and palmitoyl-protein thioesterase, an enzyme implicated in infantile neuronal lipofuscinosis. 870 98


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