Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocytosis in dystrophic muscles was studied by a combination of biochemical, radiochemical, and light and electron microscopic techniques. It was observed that the uptake of horseradish peroxidase (HRP) and 3H-Inulin in vitro was increased in leg skeletal muscles from dystrophic mice compared with littermate controls. Endocytosis of HRP in vivo was also increased in dystrophic muscles. When HRP was administered intravenously, light microscopic examination of the muscles showed that the macromolecular tracer was present not only in the extracellular space but also as intracellular deposits in several dystropic muscle fibers. Ultrastructural examination of these fibers showed HRP to be present in membrane limited bodies of variable size, some of which likely represented secondary lysosomes, located preferentially close to the A-I junction. HRP was also found inside vacuoles which were sometimes in close vicinity to autophagic vacuoles. Primary uptake vesicles containing HRP appeared to originate from the sarcolemma and the transverse tubules. Biochemical determination of lysosomal enzyme activities revealed elevated levels of both cathepsin D and N-acetylglucosaminidase in dystrophic muscles as compared with controls. The results suggest an increased endocytic activity in dystrophic muscles with distribution of exogenous marcromolecular tracers into endocytic vesicles and lysosomal structures. The hypothesis is put forward that endocytic activity constitutes an important mechanism of lysosomal activation in dystrophic muscles.
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PMID:Increased endocytosis with lysosomal activation in skeletal muscle of dystrophic mouse. 68 82

The inhibitory effect of a protein isolated from rat serum on lysosomal acid cholesteryl ester hydrolase (acid CEH; EC.3.1.1.13) activity was studied. An inhibitor was purified from rat serum following ultracentrifugation and heat treatment using column chromatography on Sephacryl S-200 and ultrafiltration. The purified inhibitor appeared as a single protein band in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The molecular weight of the inhibitor was 28,000 Daltons as judged by gel filtration on Sephacryl S-200 and SDS-polyacrylamide gel electrophoresis. The purified inhibitor was shown to be apolipoprotein A-I (apo A-I), the major apolipoprotein of high-density lipoprotein (HDL), using immunoprecipitation with rat anti-apo A-I immunoglobulin (Ig)G. Inhibition of acid CEH activity by apo A-I was dependent on the concentration of apo A-I. The values of Vmax obtained were similar with or without apo A-I. Apo A-I of various other mammalian species, including human, bovine and rabbit, also inhibited acid CEH activity. Other apolipoproteins, such as apo A-II and apo B, also showed inhibiting activity. On the other hand, apo A-I had no effect on the activity of other enzymes found in lysosomes, such as cathepsin D, beta-glucuronidase and acid phosphatase. The results suggest that apolipoproteins may play a role in the regulation of hydrolysis of cholesteryl esters in lipoproteins, that have been transferred to the liver, and that the inhibition of acid CEH activity by apo A-I may be a characteristic of the lipid-binding protein or be due to changes of the lipid/water interface.
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PMID:Properties of an acid cholesteryl ester hydrolase inhibitor from rat serum. 212 53

Tumorilysin was found in diffusion chambers implanted s.c. or i.p. in A/BiF/F50+, DBA/2J and C57BL/6J mice. Chambers with 0.45-micrometer pores implanted s.c. were most densely covered by a syncytium of macrophages and had the most consistently active tumorilysin, compared with smaller-pored chambers or those implanted i.p. The lysin acted on cultures of murine sarcomas induced by foreign bodies, murine and human mammary carcinoma, and human lymphoma. Lysis was demonstrable within 15 min. There was a dose-response relationship between residual cell counts in cultures and concentrations of diffusion chamber fluid between 1.5 and 12.5%. Murine fibroblasts in culture were not lysed by tumorilytic fluid. The incidence of sarcomas induced by 15-mm vinyl squares implanted s.c. in A/BiF/F50+ mice was significantly reduced at 64 weeks in each of 4 experiments by 2 or 3 injections of 0.05 ml diffusion chamber fluid within the capsule on each side at 2 to 42 weeks after implantation. Analyses of the fluid, compared with serum, for the following substances showed no correlation with tumorilysis: cathepsin D; neutral protease; complement C3 fraction; and arginase. Tumorilysin was preserved by lyophilization and was destroyed by heating to 56 degrees; it did not pass filters cutting off at m.w. 300,000.
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PMID:Tumorilysin collected in diffusion chambers and restraint of foreign body tumorigenesis. 698 83

It is established that isoniazid (isonicotinic acid hydrazide) can interact with A-I apolipoprotein to form a complex, which can be considered as the transport form of the preparation. The use of this complex for the treatment of mice with BCG-induced tuberculous inflammation led to an increase in the free activities of acid phosphatase and cathepsin D in the liver, which was decreased under the action of mycobacteria and the free form of isoniazid. The isoniazid complex with A-I apolipoprotein exhibited more expressed anti-inflammatory effect (estimated by the activity of chitotriosidase in blood serum) as compared to the free drug.
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PMID:[Influence of isoniazid complex with A-I apolipoprotein on activity of lysosomal enzymes in mice with tuberculous inflammation model]. 2332 30