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 activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, were measured in the gastrocnemius, soleus, and tibialis anterior muscles of rats after bilateral cast-immobilization of the muscles in lengthened and shortened positions for one and three weeks. The activities of muscular proteolytic and hydrolytic enzymes cathepsin D (CD), beta-glucuronidase (beta-GU), alkaline protease (AP), and the rate of acid autolysis (AA) were also studied. The biochemical results were compared to the morphologic changes by light microscopy. Compared to the results for a control group, there was a decrease of 37% and 53% in the specific PH activity of shortened gastrocnemius and soleus, respectively, after three weeks of immobilization. The corresponding decrease in GGT of the shortened gastrocnemius was 47%. At the same time, PH and GGT in the lengthened plantarflexors were at the control level. The proteolytic activities of the shortened plantarflexors were generally higher (CD by approximately 30%, beta-GU of gastrocnemius by 81%, AP of soleus by 63%, AA of gastrocnemius by 34%, and AA of soleus by 56%) than those of the lengthened ones. Light microscopy of the shortened muscles showed numerous atrophic fibers, but no pronounced inflammatory response in the disused muscle tissue. The results suggest that increased proteolysis and wasting of muscle tissue during cast-immobilization is associated with adaptive responses in the metabolism of the muscular collagen network.
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PMID:Collagen synthesis and proteolytic activities in rat skeletal muscles: effect of cast-immobilization in the lengthened and shortened positions. 305 21

Sporothrix schenckii, mainly in the yeast form of the organism, produced extracellular proteinases when cultivated in liquid media containing albumin or collagen as a nitrogen source, but did not do so in brain heart infusion medium. Isolation of two extracellular proteinases from albumin-containing medium was performed by chromatography on DEAE-Sepharose CL-6B and Sephacryl S-200. Proteinase I had a molecular weight of 36,500, an optimal pH at 6.0, and a pI at 4.8. Despite its activities in weakly acidic conditions, proteinase I demonstrated chymotrypsinlike characteristics, these being indicated by strong inhibitory activity by phenylmethylsulfonyl fluoride and chymostatin and good kinetic constants for a synthetic chymotrypsin substrate, Suc-Ala-Ala-Pro-Phe-MCA. Proteinase II had a molecular weight of 39,000, an optimal pH at 3.5, and a pI at 3.8. Proteinase II showed cathepsin D-like characteristics, these being indicated by strong inhibitory activity by pepstatin, an acidic optimal pH, and good kinetic constants for hemoglobin. These two enzymes hydrolyzed natural substrates such as stratum corneum, type I collagen, and elastin although not type IV collagen. Proteinase production and cell growth in collagen-containing medium and the enzymatic digestion of skin constituents by isolated proteinases suggested that these two proteinases cooperatively enable the organism to invade skin and to obtain peptides from insoluble proteins.
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PMID:Isolation and properties of extracellular proteinases from Sporothrix schenckii. 330 79

The activity of cathepsin B and D in human liver biopsy specimens from cirrhotic patients before and after one year of colchicine treatment was studied. The hydroxyproline content as a marker of the amount of collagen in tissue specimens was also determined. The hydroxyproline content in the liver samples was two or threefold that of the control group. After colchicine it remained unchanged or in some patients its values were decreased. Cathepsin B activity was higher in cirrhotic liver samples as compared with the controls, whereas the increased activity of cathepsin D was not significant. The ratio of cathepsin B and D activity to hepatic hydroxyproline content was significantly reduced in cirrhotic livers. Colchicine treatment was followed by an increase in the levels of the enzymes investigated as well as by a significant rise in the ratio of cathepsin B and D activity to hepatic hydroxyproline content.
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PMID:Effect of colchicine on the activity of cathepsin B and D in human liver cirrhosis. 368 46

1. Experiments were made to determine whether the purified lysosomal proteinases, cathepsins B1 and D, degrade acid-soluble collagen in solution, reconstituted collagen fibrils, insoluble collagen or gelatin. 2. At acid pH values cathepsin B1 released (14)C-labelled peptides from collagen fibrils reconstituted at neutral pH from soluble collagen. The purified enzyme required activation by cysteine and EDTA and was inhibited by 4-chloromercuribenzoate, by the chloromethyl ketones derived from tosyl-lysine and acetyltetra-alanine and by human alpha(2)-macroglobulin. 3. Cathepsin B1 degraded collagen in solution, the pH optimum being pH4.5-5.0. The initial action was cleavage of the non-helical region containing the cross-link; this was seen as a decrease in viscosity with no change in optical rotation. The enzyme also attacked the helical region of collagen by a mechanism different from that of mammalian neutral collagenase. No discrete intermediate products of a specific size were observed in segment-long-spacing crystalloids (measured as native collagen molecules aligned with N-termini together along the long axis) or as separate peaks on gel filtration chromatography. This suggests that once an alpha-chain was attacked it was rapidly degraded to low-molecular-weight peptides. 4. Cathepsin B1 degraded insoluble collagen with a pH optimum below 4; this value is lower than that found for the soluble substrate, and a possible explanation is given. 5. The lysosomal carboxyl proteinase, cathepsin D, had no action on collagen or gelatin at pH3.0. Neither cathepsin B1 nor D cleaved Pz-Pro-Leu-Gly-Pro-d-Arg. 6. Cathepsin B1 activity was shown to be essential for the degradation of collagen by lysosomal extracts. 7. Cathepsin B1 may provide an alternative route for collagen breakdown in physiological and pathological situations.
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PMID:Cathepsin B1. A lysosomal enzyme that degrades native collagen. 420 88

1. An enzyme present in rat liver extracts degraded insoluble collagen maximally at pH3.5. Collagenolytic activity was more abundant in kidney, spleen and bone marrow and was also present in decreasing concentrations in ileum, lung, heart, skin and muscle. 2. The crude collagenolytic cathepsin was activated by cysteine and dithiothreitol, but not by 2-mercaptoethanol. Iodoacetamide, p-chloromercuribenzoate and 7-amino-1-chloro-3-l-tosylamidoheptan-2-one hydrochloride inhibited the enzyme. Zn(2+), Fe(3+) and Hg(2+) ions were strongly inhibitory, but Ca(2+), Co(2+), Mg(2+) and Fe(2+) ions had little or no effect. EDTA was an activator of the enzyme. Inhibitors of cathepsin B were found to enhance collagenolysis, but phenylpyruvic acid, a cathepsin D inhibitor, inhibited the enzyme. Di-isopropyl phosphorofluoridate had no effect. 3. Collagenolysis at pH3.5 and 28 degrees C was restricted to cleavage of the telopeptide region in insoluble collagen, and the material that was solubilized consisted mostly of alpha-chains. 4. The collagenolytic cathepsin was separated from cathepsins B2 and D by fractionation on Sephadex G-100 and a partial separation from cathepsin B1 was obtained by chromatography on DEAE-Sephadex. 5. The function of the collagenolytic cathepsin in the catabolism of collagen is discussed in relation to the action of the other lysosomal proteinases and the neutral collagenase.
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PMID:The nature of the collagenolytic cathepsin of rat liver and its distribution in other rat tissues. 465 Nov 35

1. The earlier observation (Woessner, 1969) of oestradiol inhibition of collagen breakdown is confirmed and extended. Administration of 100mug of oestradiol-17beta/day to parturient rats strongly inhibits the loss of collagen from the involuting uterus. Three experiments show that this effect is due to an inhibition of collagen degradation rather than to a stimulation of collagen synthesis. 2. Uterine collagen was labelled with hydroxy[(14)C]-proline by the administration of [(14)C]proline near the end of pregnancy. By 3 days post partum, control uteri lost 83% of their collagen and 90% of their hydroxy[(14)C]proline. Uteri from oestradiol-treated rats lost only 50% of both total and labelled hydroxyproline, with no decrease in the specific radioactivity of the hydroxyproline. 3. Incorporation of [(14)C]proline into uterine collagen hydroxyproline in vivo was not affected by oestradiol treatment. 4. Urinary excretion of hydroxyproline was increased in post-partum control rats and decreased in oestradiol-treated rats. 5. An enzyme capable of cleaving 4-phenylazobenzyloxycarbonyl-l-prolyl-l-leucylglycyl- l-prolyl-d-arginine (a substrate for clostridial collagenase) increased in activity in the post-partum uterus and was unaffected by oestradiol treatment. 6. Uterine homogenates digested uterine collagen extensively at pH3.2. This digestion was unaffected by the oestradiol treatment. 7. Lysosomal fractions prepared by density-gradient centrifugation of uterine homogenates contained coincident peaks of cathepsin D activity and peptide-bound hydroxyproline. The cathepsin D and hydroxyproline contents of this peak were unaffected by oestradiol treatment.
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PMID:Oestradiol inhibits collagen breakdown in the involuting rat uterus. 465 Nov 36

1. An enzyme system present in a rat liver lysosome-rich fraction was found to liberate soluble hydroxyproline-containing products from insoluble collagen, with maximum activity at pH3.45. It was concluded that a form of cathepsin D was involved since synthetic substrates specific for trypsin were not hydrolysed. Collagenolysis was enhanced by thiol compounds and inhibited by Cu(2+) ions and the anti-inflammatory drugs phenylbutazone and ibufenac. 2. The possibility that behaviour of collagen and collagenolysis were modified by various substances, either by destruction of intramolecular and intermolecular bonds in tropocollagen or by electrostatic interactions, is discussed. Insoluble collagen was found to bind electrostatically to chondromucoprotein. This interaction was inhibited by some anti-inflammatory drugs. 3. Possible roles of the lysosomal collagenolytic enzyme system in experimental lathyrism in rats given penicillamine, and in erosion of cartilage in rheumatoid arthritis, are considered. 4. Collagenolysis in vivo, which may depend on complex interrelationships between collagen, chondromucoprotein and metal ions, is discussed in relation to possible effects, both harmful and beneficial, of anti-inflammatory drugs used in rheumatoid arthritis.
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PMID:Effects of lysosomal collagenolytic enzymes, anti-inflammatory drugs and other substances on some properties of insoluble collagen. 580 7

1. Both the post-partum involution of the rat uterus and the rapid breakdown of collagen that accompanies it are extensively inhibited by oestrogenic hormones. In the normal rat, 85% of the uterine collagen is degraded within 4 days after parturition; in rats treated with 100mug. of 17beta-oestradiol/day, only 35% of uterine collagen is broken down in the same period. 2. Similar effects are produced by diethylstilboestrol if the dose is increased tenfold. 3. Collagen breakdown is inhibited to a greater extent than is the loss of wet weight by oestradiol but not by diethylstilboestrol. 4. The oestrogens appear to act by blocking the breakdown of collagen. There is a greatly decreased concentration of free hydroxyproline in the uterus of treated animals. 5. Acid hydrolase concentrations (beta-glucuronidase, beta-galactosidase, cathepsin D and acid phosphatase) in the uterus are decreased by oestrogen treatment compared with controls, but the total amounts of these enzymes in the uterus are somewhat elevated. Oestrogens do not appear to inhibit collagen breakdown by altering the concentration and total amount of acid hydrolases.
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PMID:Inhibition by oestrogen of collagen breakdown in the involuting rat uterus. 582 64

Bovine basic protein (BP) was digested with purified bovine brain cathepsin D to produce well defined BP derived peptides 1-42, 43-88, 43-169, and 89-169. BP and these BP peptides were tested for their effects on cultured human dermal fibroblasts using a concentration range of 0.01-1,000 ng/ml. No effect was found on cellular proliferation, and neither total protein nor collagen synthesis was altered in the presence of these substances. Although preparations of brain which contain a fibroblast-growth factor also contain BP peptides, these results indicate that the purified BP peptides studied have no detectable biological effect on the growth of human dermal fibroblasts.
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PMID:Effect of peptides of bovine myelin basic protein on dermal fibroblasts. 616 Feb 57

The activity of collagenase, cathepsin B1, cathepsin D and Hyaluronidase was determined in skin, bone, liver, kidney, spleen and serum of adjuvant induced arthritic rats during the acute and chronic phase of the disease. Collagenase was assayed directly in tissue extract by a solution method using radioactive labelled substrate. The activity of collagenase, cathepsin B1 and D was found to increase significantly at both phases of the disease. The activity of hyaluronidase decreased significantly in liver, kidney and spleen of arthritic rats, while in skin, bone and serum no significant change was observed. The results are discussed with respect to catabolism of collagen in adjuvant induced arthritis. Prednisolone and L-thyroxine were administered to arthritic rats and the activity of collagenase, cathepsin B1, cathepsin D and hyaluronidase was determined in the treated groups during the acute and chronic phase of the disease. Prednisolone was found to suppress the development of arthritis which, in turn, decreased the increased activity of collagenase and lysosomal enzymes cathepsin B1 and D in tissues and serum of arthritic rats. L-Thyroxine was found to slowly diminish the development of inflammation and its beneficial action was found in mesenchymal tissues and skin of arthritic rats but not in bone.
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PMID:Effect of adjuvant arthritis on collagenase and certain lysosomal enzymes in relation to the catabolism of collagen. 624 97


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