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)

A neutral proteinase secreted by rabbit synovial fibroblasts in parallel with specific collagenase was partially purified by ion-exchange chromatography. At pH 7.6 this proteinase degraded 35S-labelled bovine nasal proteoglycan and azo-casein. The enzymic activity was inhibited by EDTA, 1,10-phenanthroline and serum, whereas di-isopropyl phosphorofluoridate and soya-bean trypsin inhibitor had little effect. By gel filtration the apparent mol.wt. of the enzyme was 25000. The fibroblast neutral proteinase was compared with the proteoglycan-degrading neutral proteinases of rabbit polymorphonuclear-leucocyte granules. Two distinct activities were found in the granules: one was inhibited by soya-bean trypsin inhibitor and the other by EDTA. The proteoglycan-degrading proteinases of rabbit fibroblasts and polymorphonuclear leucocytes at acid pH also were examined. Both cathepsin D and a thiol-dependent proteinase contributed to the degradation of proteoglycan at pH 4.5.
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PMID:Proteoglycan-degrading enzymes of rabbit fibroblasts and granulocytes. 3 Apr 51

Cathespin D from the retinal pigment epithelium of bovine eyes was purified about 25-fold from a crude extract of retinal pigment epithelium by acid treatment, ammonium sulfate fractionation, and Sephadex G-200 column chromatography. The purified enzyme hydrolyzed bovine serum albumin optimally at pH values close to 4.0. Exposure of the enzyme to 60 degrees C. for 2 minutes resulted in 50 per cent inactivation of the activity. The enzyme activity was completely inhibited by 0.1 microgram per milliliter of pepstatin, slightly inhibited by trasylol, and not affected by soybean trypsin inhibitor. The apparent molecular weight of cathepsin D was estimated to be about 60,000 by gel filtration on Sephadex G-200.
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PMID:Partial purification and properties of cathepsin D in the retinal pigment epithelium. 108 Jan 46

A novel effective procedure for the purification of cathepsin D inhibitor from potatoes (PDI) was developed. The amino acid sequence of PDI was determined by analysis of the cyanogen bromide digest and of the limited tryptic and chymotryptic digest of the protein. The inhibitor is a single polypeptide chain protein consisting of 188 residues with a simple sugar moiety attached to Asn-19. The tentative disulfide pairings are also suggested. The sequence data clearly indicate that PDI is homologous with the soybean trypsin inhibitor (STI) (Kunitz) family. The active center of PDI for trypsin inhibition was identified as Pro-Val-Arg-Phe in analogy to STI.
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PMID:Primary structure of cathepsin D inhibitor from potatoes and its structure relationship to soybean trypsin inhibitor family. 275 67

We have identified a system in human lymphocytes which proteolytically cleaves poly(ADPribose) polymerase to specific fragments of molecular weight 96 000, 79 000 and 62 000-60 000. This proteolytic processing is dependent on two different classes of proteinase. One of these proteinases is a serine proteinase, since the processing is inhibited by phenylmethylsulfonyl fluoride, antipain, soybean trypsin inhibitor and diisopropylfluorophosphate, the other is a cathepsin D-like proteinase, since processing is also inhibited by pepstatin A. The processing that occurs in permeabilized cells can be simulated in vitro by treating purified poly(ADPribose) polymerase with trypsin, but not by treating the polymerase with cathepsin D. Since processing at the cellular level is blocked by inhibitors of either of the two proteinases, but only trypsin could cleave the purified polymerase, this suggests that in the cell the action of the cathepsin D-like proteinase is a prerequisite for cleavage of poly(ADPribose) polymerase by the serine proteinase. Thus, a pathway involving sequential action of these proteinases may exist. Proteolysis in permeabilized human lymphocytes is stimulated by nucleotides containing a pyrophosphate group, such as 5',5'''-P1,P4-tetraphosphate and ATP, or by pyrophosphate itself. In contrast, nucleotides containing only a single phosphate, such as AMP and cyclic AMP, or inorganic sodium phosphate, do not show this stimulation of proteolysis. These results suggest that a pyrophosphate linkage is the minimum molecular requirement for stimulation of proteolytic processing of poly(ADPribose) polymerase. Proteolytic processing of poly(ADPribose) polymerase is independent of ADPribosylation. Following proteolysis, specific fragments of the polymerase, particularly the 62 000-60 000 molecular weight fragment(s), are still capable of being ADPribosylated.
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PMID:Proteolysis of poly(ADPribose) polymerase by a pyrophosphate- and nucleotide-stimulated system dependent on two different classes of proteinase. 299 8

T-kininogenase (T-kgnase) activity has been investigated in tissues of the rat and submandibular glands of the rat, mouse and guinea pig. Both rat and mouse submandibular homogenates showed high T-kgnase activity. The enzyme has been purified 360-fold from rat submandibular gland homogenate supernatant fluid. The enzyme has an apparent molecular mass of 28 kDa and a pH optimum of 8.0 toward T-kininogen. It cleaved T-kininogen in catalytic quantities to release T-kinin (Ile-Ser-bradykinin) and small quantities of bradykinin and an unknown kinin. The activity of the enzyme was increased 10-fold in the presence of thiol groups (dithiothreitol) and inhibited by leupeptin (90%) and to a lesser extent by aprotinin (49%), TLCK (46%) and soybean trypsin inhibitor (27%). Pepstatin and PMSF did not inhibit the enzyme. Studies on substrate specificity, pH optimum and agents which inhibit T-kgnase activity demonstrate that this enzyme is different from plasma and tissue kallikreins, cathepsin D, esterase A and esterase B (other known kininogenases). It is the first thiol-activated kininogenase to be reported.
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PMID:Isolation of a thiol-activated T-kininogenase from the rat submandibular gland. 364 75

We have studied the dog as a potential model for the human plasma prorenin-renin system. On a regular sodium intake, healthy conscious dogs apparently have a much lower plasma renin activity (PRA) than healthy human volunteers. Cryoactivation of prorenin is virtually absent in dogs, in contrast to that in humans, but becomes more effective after preacidification of the plasma. The concentration of trypsin required for optimal activation of prorenin is 6 to 10 times higher for dog plasma, revealing a prorenin:renin ratio about 10 times greater than in humans. Dialysis of posttryptic plasma decreases the PRA, but it remains 5 times higher than in pretryptic plasma, indicating that activation is not totally dependent on any renin system component that has been rendered dialyzable by trypsin, e.g., substrate converted to tetradecapeptide (TDP). This argues against the view that tryptic activation is attributable to angiotensin production from TDP by the action of cathepsin D, rather than from new renin converted from prorenin. The posttryptic increase in PRA is evident whether plasma incubation is carried out at pH 6.0 or at 7.4, and can be largely blocked by pepstatin, which also implicates a prorenin-renin mechanism rather than TDP-cathepsin. The low PRA in dogs, the negligible cryoactivation and its improvement by preacidification, and the requirement and tolerance of high trypsin concentrations, all point to greater protease inhibition in dog plasma and/or departures from the enzyme(s) responsible for human prorenin activation. Moreover, the tryptic activation of prorenin is not completed quickly as in human plasma, but carries over into the posttryptic stage of angiotensin generation, even in the presence of excess soybean trypsin inhibitor (SBTI), and other potent inhibitors. Such ongoing prorenin activation cannot be attributed only to trypsin itself, nor to kallikrein (both are inhibited by SBTI), but rather to some other enzyme(s) derived by the action of trypsin. This new prorenin convertase activity (possibly renin itself) can be effectively transferred from trypsinized to control dog plasma, in which it greatly accelerates prorenin activation. Thus, contrary to other reports, dog plasma has a high content of activatable prorenin, and with appropriate methodological changes, the dog can be used as an animal model for physiological and biochemical studies of the prorenin-renin system.
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PMID:Plasma prorenin in humans and dogs. Species differences and further evidence of a systemic activation cascade. 634 Dec 16

The inhibitory effect of thermo- and acid-resistant inhibitor of trypsin, chymotrypsin and leukocyte proteinases (TASPI) from rabbit serum on the kininogenase activity of cathepsins D from different organs and tissues (human spleen and liver, chicken liver, spleen leukemic infiltrate from patients with myeloid leukemia) was revealed. The progressive mechanism of TASPI and cathepsins D complexation dependent on time and temperature was revealed. The rate constant of inhibition (ki) of chicken liver cathepsin D by TASPI at 37 degrees was 4,25.10(3)M-1 min-1. It was shown that the kininogenase activity of chicken liver cathepsin D was slightly inhibited by the basic pancreatic trypsin and kallikrein inhibitor from bovine organs (Kunitz type) and by soya bean trypsin inhibitor. The role of TASPI as regulator of cathepsins D activity under pathological conditions accompanied by lysosomal disintegration is discussed.
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PMID:[Inhibition of kininogenase activity of cathepsins D by acid-resistant proteinase inhibitor from rabbit serum]. 691 92

The effects of inhibitors on the kinin-forming enzyme (KFE) activity in the rat stomach were investigated at pH 4.8. The KFE activity was unaffected by trasylol (200 KIU/ml), soybean trypsin inhibitor (100 microgram/ml) and p-tosyl-L-lysine-chloromethyl ketone (10-3 M), but was inhibited by pepstatin A (10(-6) M) and chymostatin (1.5 x 10(-4) M). Each product from the rat plasma kininogen by the rat stomach KFE and the bovine spleen cathepsin D was eluated at the same retention time on the equilibrium chromatography on the SP-Sephadex C-25 column. The KFE activity in the rat stomach was considerably high compared with that in various regions of the intestine. These results suggest that the KFE is characteristically similar to cathepsin D, and the enzyme is probably relevant to the function of the stomach.
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PMID:Property of kinin-forming enzyme in rat stomach. 691

Two trypsin inhibitor types, PII and PI II, were isolated by affinity chromatography of a potato extract on a column of trypsin immobilized on Sepharose 4B. Fraction PI I afforded after ion exchange chromatography on SE-Sephadex two isoinhibitors, PI IA (Mr approximately 18 000; pI approximately 6.3) and PI IB (Mr approximately 19 500; pI approximately 7.2). The chromatography of fraction PI II on SE-Sephadex yielded three inhibitors of approximately equal molecular weight (Mr approximately 13 500), PI IIC (pI approximately 6.3), PI IID (pI approximately 7.7), and PI IIE (pI approximately 9.1). All the inhibitors isolated show a high activity toward trypsin, acrosin, and chymotrypsin. Unlike the two isoinhibitors of PI I, which practically do not inhibit kallikrein, inhibitors PI II show an effect on this enzyme. Neither the isoinhibitors of PI I nor inhibitors PI II are active toward cathepsin D.
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PMID:Polyvalent proteinase inhibitors from potatoes. Isolation and characterization of acrosin inhibitors from Solanum tuberosum. 704 Jan 19

Trypsin inhibitor was isolated from the vegetative portion of alfalfa and purified 270-fold by affinity chromatography on Trypsin-Sepharose. The inhibitor was eluted by gel-filtration as a single peak with molecular weight of 6900. Disc-electrophoresis of the purified inhibitor revealed the presence of only one protein band. Trypsin inhibition is a mixed process. The trypsin inhibitor from alfalfa does not prevent the activity of cathepsin D from bovine brain. Trypsin inhibitor was immobilized on BrCN-activated Sepharose 4B. The binding of trypsin to the immobilized trypsin inhibitor was studied: 5 mg of the immobilized trypsin inhibitor were found to bind 1 mg of trypsin.
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PMID:[Purification and properties of inhibitor from vegetative portion of alfalfa]. 727 46


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