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 interrelation between intracellular cAMP content and activity of lysosomal hydrolases was studied in rat liver and heart during ischemia of varying genesis and after recirculation. The activity of acid phosphatase (AP) and cathepsin D (CD) was determined in the fraction enriched with lysosomes (FEL) and in the supernatant fraction (SF) at 30,000 x g. Ischemia of isolated perfused heart of 20 to 60 min as described by Langendorff was accompanied by an increase in the SF/FEL ratio. Postischemic reperfusion resulted in a further increase in this ratio. In a terminal state induced by cardiac arrest of 10 min and within the first postresuscitation hours the SF/FEL ratio in the rat liver also increased. Processing of the liver FEL with 0.025% concentration of detergent Triton X-100 was also indicative of lability of lysosomal membranes during recirculation. The intracellular cAMP content changed differently. During ischemia of the myocardium, the cAMP level rose by 40 min and remained increased after 20 and 40 min of reperfusion. The cAMP content in the liver decreased after 10 min of circulatory arrest and increased in the postresuscitation period achieving its peak 4 h after resuscitation. Intra-abdominal injection of lyposomes with incapsulated cAMP to rats in the postresuscitation period and the study of the effect of dibutyryl-cAMP, caffeine and isoproterenol on the activity of acid hydrolases of ischemic heart and after postischemic reperfusion showed that an increase in the cAMP content achieved in various ways was conducive to stabilization of lysosomal membranes.
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PMID:Role of cAMP in regulation of activity of acid hydrolases of rat heart and liver during ischemia and after recirculation. 166 65

The influence of cardioselective beta-blockers, practolol and atenolol, on acid phosphatase, acid deoxyribonuclease, cathepsin D, beta-glucosidase and beta-galactosidase activities was studied in homogenates of intact rat ventricular myocardium. In the presence of drugs (1 x 10(-9)-1 x 10(-5) M) the activities of acid phosphatase, cathepsin D, beta-glucosidase and beta-galactosidase tended to diminish but the activity of acid deoxyribonuclease tended to increase. Some differences in the influence of drugs on the enzyme activities were removed by prolongation of preincubation of homogenates with drugs. It is supposed that the mechanism of influence of beta-blockers on lysosomes of the intact rat ventricular myocardium in conditions of this study includes the specific drug binding to beta-adrenergic receptors situated on lysosomes.
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PMID:[The effect of practolol and atenolol on the lysosomal enzyme activity of the ventricular myocardium of rats]. 166 75

Two different performed HSA-anti-HSA immune aggregates, insoluble complex at equivalence (IC-E) and soluble complex with 5 times antigen excess (IC-S)-were administered iv in experimental mice to study their interaction with liver cells. Both complexes produced no appreciable change in the levels of liver enzymes like acid phosphatase, cathepsin D and gamma-glutamyl transferase. However, marked reduction in the level of liver pseduocholinesterase (as much as 93%) was recorded in the treated animals under identical conditions of administration of both the complexes. Hepatic uptake studies revealed that within 5 min, maximal sequestration of IC occurred within the liver (10 to 18%) and the blood (70 to 82%) when computed in terms of total injected radioactive IC. After 4 h, radioactivity dropped to 3 per cent in liver and 50-40 per cent in blood. The liver seemed to be incapable of scavenging all the serum complexes at a time. Significant consumption of serum complement occurred, when freshly prepared complexes were administered to the animals, but the reduced complement level showed a tendency to reach normalcy after 2 h. The soluble and equivalence zone IC failed to exhibit identifiable discrimination facets with respect to handling by liver. The complexes IC-E and IC-S also behaved in a similar manner.
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PMID:Effects of preformed immune complexes on liver enzymes & their serum clearance in mice. 168 48

The biosynthesis, processing, and intracellular transport of lysosomal acid phosphatase was studied using an in vitro cell-free translation system, pulse-chase experiments with primary cultured rat hepatocytes and subcellular fractionation techniques of rat liver after pulse-labeling with [35S]methionine in vivo. The single polypeptide of 45 kDa translated in the cell-free system from membrane-bound polysomal RNAs was converted to the 64 kDa form when the translation was carried out in the presence of microsomal vesicles. Pulse-chase experiments using cultured rat hepatocytes showed that acid phosphatase is initially synthesized as an endo-beta-N-acetylglucosaminidase H (Endo H)-sensitive form of 64 kDa, and processed via an Endo H-sensitive intermediate form of 62 kDa to an Endo H-resistant form with a 67 kDa mass. Phase separation with Triton X-114 showed that both the 64 and 67 kDa forms have hydrophobic properties. Treatment of the cells with chloroquine or tunicamycin, drugs which enhance the secretion of lysosomal hydrolases, had no effect on the normal transport of acid phosphatase to lysosomes. Acid phosphatase did not contain the phosphorylated high mannose type of oligosaccharide chains observed in cathepsin D. Subcellular fractionation experiments in conjunction with pulse-labeling in vivo showed that the acid phosphatase of the 67 kDa form was present in the Golgi heavy fraction (GF3) and the Golgi light fraction (GF1+2) enriched in cis and trans Golgi elements, respectively, at 30 min after the administration of [35S]methionine. Simultaneously, this polypeptide was also found in the lysosomal membrane fraction, thereby indicating that acid phosphatase is delivered to lysosomes in a membrane-bound form, immediately after reaching the trans-Golgi region.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biosynthesis, processing, and intracellular transport of lysosomal acid phosphatase in rat hepatocytes. 169 35

1. Chloroquine accumulation in rat liver after a single and repeated drug administration and lysosomal changes resembling some symptoms of lysosomal storage diseases were observed. 2. Repeated chloroquine treatment of rats resulted in increased activity of liver lysosomal enzymes acid phosphatase and beta-galactosidase and a significant enhancement of the activities of cathepsin D and cysteine proteinases were found. 3. No changes in the activity of liver macrophages (as assessed by the colloidal carbon clearance test) or in fluid-phase endocytosis of the marker 125I-polyvinyl-pyrrolidone by hepatocytes in vivo were found.
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PMID:Effects of chloroquine on lysosomes and endocytosis by liver cells in vivo. 184 18

Unicameral bone cyst fluid possesses N-acetyl-beta-D-glucosaminidase, beta-glucuronidase, PZ-peptidase, cathepsin D, acid phosphatase, N-acetyl-beta-D galactosaminidase, and beta-galactosidase activities. The activities of lysosomal enzymes in the cyst fluid are, as a rule, higher than in the serum, whereas the total protein content is lower. The content of collagen degradation products in the cyst fluid is higher compared to the serum. In bone cavity wall tissues, the collagen content is decreased. Adenosine 3':5'-cyclic phosphate and cyclic guanosine 3,5'-monophosphate accumulate in the cyst cavity. However, in some cases, there is no correlation among the activities of lysosomal enzymes in the cyst fluid, blood serum, and cyst wall tissues. The ratios of lysosomal enzyme activities in the cyst fluid differ from those in the cyst wall tissues, cultured skin fibroblasts, and blood polymorphonuclear leucocytes. The lack of coincidence of enzymatic spectra of the cyst fluid, wall tissues, and serum is suggestive of the diversity of ways of lysosomal enzyme enter the cyst cavity, i.e., blood, cyst fluid cells, and cyst cavity walls. The cysts with different locations (i.e., active and latent cysts) have similar lysosomal lytic potentials. The presence in the cyst cavity of extracellular lysosomal enzymes and collagen degradation products testifies to the permanent corrosion of the cyst cavity walls from the inside as well as to the increase in the osmotic pressure of the cyst fluid. Lysosome destruction should be regarded as an important pathogenetic factor that requires surgical or pharmacologic correction or both in the course of bone cyst management.
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PMID:The role of lysosomes in the pathogenesis of unicameral bone cysts. 185 Mar 36

Adherent cultures of rat peritoneal macrophages secrete lysozyme and the lysosomal marker enzymes beta-glucuronidase, beta-N-acetylglucosaminidase and acid phosphatase; the levels of secreted lysosomal cathepsin D, however, were found to be insignificant. Incubation of the cells at 4 degrees C for 15 min with yeast mannan or with 50 mM mannose, methyl alpha-glucopyranoside, or N-acetylglucosamine caused the concentration of cathepsin D in the culture medium to increase 30-40-fold; mannose-6-phosphate had no effect. 125I-labeled cathepsin D was prepared and the binding constant to the macrophage cell surface was determined to be KD = 27 nM. The data suggest that cathepsin D binds to the mannose receptor of macrophages and that binding to this receptor is not in equilibrium with the bulk medium.
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PMID:Binding of cathepsin D to the mannose receptor on rat peritoneal macrophages. 193 26

The effect of NCO-700 (1), a protease inhibitor, on subcellular distribution of lysosomal enzymes was studied in the ischemic perfused rat heart. Ischemia was induced by lowering the afterload pressure of the working heart preparation. The subcellular distribution of lysosomal enzymes was estimated by the ratio of the activities of cathepsin D, beta,N-acetylglucosaminidase, and acid phosphatase in the cytoplasm to the total enzyme activities. Ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm, indicating the rupture of lysosomes. Compound 1 (1.75 x 10(-4) M) was provided for the heart 5 min before the onset of ischemia. Compound 1 appeared to inhibit the rupture of lysosomes being caused by ischemia. The mechanism by which 1 protects the myocardium against ischemic injury may involve the inhibition of lysosomal rupture in the ischemic myocardium.
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PMID:Effect of NCO-700, an inhibitor of protease, on lysosomal rupture in the ischemic myocardium. 205 42

We examined the mechanism of release of acid phosphatase (APase) from lysosomal membranes into the lysosomal matrix. When rat liver lysosomal membranes were incubated at various pH values with APase-free tritosomal contents prepared by the treatment of tritosomal contents with anti-APase IgG Sepharose, 86% of the APase activity in the lysosomal membranes became soluble at pH 5.0. Immunoblots revealed that the membrane-bound APase (67 kDa) was released in a 64 kDa form, and the 67 and 64 kDa forms were converted to 45 and 41 kDa forms by Endo F treatment, respectively, thereby indicating that the release of APase from the lysosomal membranes was accompanied by a limited proteolysis involving loss of a 4 kDa fragment. The release of APase was strongly inhibited by pepstatin A, a potent inhibitor of aspartyl protease, but other inhibitors such as leupeptin, antipain, Ep-475 and 1,10-phenanthroline showed no effect. The release of APase did not occur when the lysosomal membranes were incubated with the tritosomal contents free of APase and cathepsin D, prepared by treatment of the APase-free tritosomal contents with anti-cathepsin D IgG Sepharose. The purified lysosomal cathepsin D released 71% of the APase activity from the lysosomal membranes and the released APase had a molecular mass of 65 kDa, that is, larger than the enzyme released by using the APase-free tritosomal contents. Endo F converted the 65 kDa form to the 43 kDa form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of acid phosphatase from lysosomal membranes by cathepsin D. 212 27

Kinetics of sanguiritrine consumption by L cells of LSM substrain was studied in cell culture. About half of the drug used was absorbed by cells within 20 min. Sanguiritrine inhibited the lysosomal hydrolases (cathepsin D, beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase) activity by 50% at concentration 2.10(-4) M. The drug a concentration 4.10(-4) M inhibited acid lipase by 55% and acid phosphatase by 58%.
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PMID:[Effect of sanguiritrine on the functional activity of fibroblast lysosomes]. 212 88


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