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)

Tonin, a proteolytic enzyme isolated from rat submaxillary gland, was allowed to react upon ovine beta-lipotropin (beta-LPH) at 37 degrees C at a variety of pH values and for different lengths of time. Opiatelike activity generated by the reaction was assessed using a radioreceptor assay for beta-endorphin with rat brain homogenate. [3H]naloxone, and beta-endorphin as receptors, tracer, and hormone standard, respectively. Cleavage of beta-LPH with tonin produced a 10-fold increase in opiatelike activity as compared with beta-LPH alone. Digestion of beta-LPH with other enzymes such as renin, cathepsin D, trypsin, and chymotrypsin produced much less opiatelike activity. beta-Endorphin and methionine-enkephalin were not cleaved by tonin. Using this new assay, we were able to detect beta-LPH and materials containing opiatelike activity from rat pituitary extracts after gel chromatography. It is more specific and more sensitive than trypsin digest.
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PMID:Detection from rat pituitary of beta-lipotropin and materials containing opiatelike activity by combined enzymatic radioreceptor assay. 627 75

The proteolytic activity in homogenates and extracts of subcellular fractions prepared from subcutaneous Lewis lung carcinoma was determined using proteins and synthetic peptides as substrates. The presence of cathepsin D, plasminogen activator, cathepsin B-, cathepsin G- and elastase-like enzymes was observed. No difference was revealed between the proteolytic activity in homogenates of Lewis lung carcinoma, at the growth stage examined, and in homogenates of normal lung. High specific activities were found in the lysosomal extract, whereas decreasing activities were found in the nuclear extract, the homogenate and the postlysosomal mitochondrial supernatant; no active or trypsin-activatable collagenase activity was detected. The presence in the tumor tissue of these enzymatic activities is in agreement with their proposed role in the process of metastasis. The lack of differences between homogenates of tumor and normal lung tissue suggests that the use of whole cells is required to selectively study tumor proteinases specifically involved in tumor malignancy.
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PMID:Methodologic problems encountered in the assay of proteinases in Lewis lung carcinoma, a mouse metastasizing tumor. 629 35

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

A method for the preparation of casein labelled with the 4-methylumbelliferyl fluorophore is described, and the product was used as a fluorigenic macromolecular substrate for a sensitive assay of the activity of proteinases. Nanogram quantities of trypsin, chymotrypsin, elastase and cathepsin D can be detected, but the substrate is unaffected by cathepsin B.
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PMID:Fluorigenic method for the assay of proteinase activity with the use of 4-methylumbelliferyl-casein. 634 7

This review summarizes our knowledge of pituitary endopeptidases. Emphasis has been placed on well-characterized enzymes and their potential roles in proteolytic processes of the pituitary. Because of space limitations, degradation of biologically active peptide by crude preparations has generally not been discussed. Only a few proteolytic enzymes are at present adequately characterized, and knowledge of their physiological function in vivo is insufficient. Among the many functions of proteolytic enzymes, those that are specific for the pituitary as an endocrine gland are of primary interest. Such functions include inactivation of neuropeptides and factors that control the secretory function of the pituitary, processing of precursors destined for secretion, selective cleavage of prohormones into active fragments, and degradation of inactive fragments. While some of the enzymes described here, such as cathepsin D, could be expected to have primarily a degradative function, others could potentially be involved in hormonal metabolism, since they exhibit trypsin-like, chymotrypsin-like, and dipeptidyl carboxypeptidase-like activities, all potentially useful in hormonal conversions. Data suggestive of the presence in the pituitary of enzymes involved in removal of the 'signal sequence', and enzymes involved in hormone processing by cleavage of bonds after a pair of basic residues and in the subsequent removal of these residues by a carboxypeptidase B-like activity have been published. None of these enzymes, however, has been isolated or purified to a degree that would allow determination of its specificity, mechanisms of action, physicochemical properties, and susceptibility to specific inhibitors. Questions that remain unresolved ask whether differences in the processing pathways in various anatomical parts of the pituitary are due to the presence of proteases with different specificities, or to different disposition of these enzymes, and factors, such as conformation of the substrate and its secondary modification, for example by glycosylation or phosphorylation. Proof of a functional involvement of a protease in hormonal processing should include demonstration that inhibition of activity results in inhibition of processing in the intact cell. Specific inhibitors of processing enzymes could potentially be used to modulate pituitary function, and thus have pharmacological interest. Although there are few answers to the above problems at present, the questions are well defined, and it can be expected that the rapidly expanding research on pituitary proteases will soon provide some of the answers.
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PMID:Pituitary endopeptidases. 634 52

Prokallikrein was activated by trypsin and by alpha-chymotrypsin, but not by proteases, such as plasmin, thrombin, urokinase, carboxypeptidase B, papain, elastase, pepsin, and cathepsin D. Moreover, rat fresh serum did not activate prokallikrein. Maximum activation of prokallikrein by trypsin was obtained at the concentration of 10 micrograms to 1 mg per ml in PBS and that by alpha-chymotrypsin was at the concentration of 5 mg per ml. The enzymic properties of trypsin-activated and alpha-chymotrypsin-activated kallikreins were identical with those of active kallikrein in the kidney.
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PMID:Activation of prokallikrein in the rat kidney by proteases. 637 43

We developed new sensitive direct radioimmunoassay for human plasma renin. Renin was purified from Haas' preparation utilizing a pepstatin-C6-Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from our assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation (r = 0.78, p less than 0.01), but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension (0.7 to 1.7 ng/ml) was not significantly different from values in normal controls (0.8 to 1.9 ng/ml). The values were higher in patients with renovascular hypertension (1.6 to 2.7 ng/ml), malignant hypertension (2.8 to 3.4 ng/ml) and Bartter's syndrome (1.8 to 2.5 ng/ml), but lower in patients with primary aldosteronism (0.4 to 0.8 ng/ml) than in normal controls. This newly developed radioimmunoassay for human renin was sensitive enough to estimate the levels of renin in plasma of patients with low renin hypertension. It provides a new tool for the understanding of the renin-angiotensin system under various clinical conditions.
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PMID:A new sensitive direct radioimmunoassay for human plasma renin and its clinical application. 638 35

An inhibitor of lysosomal acid cholesteryl ester hydrolase (Acid CEH), (EC 3.1.1.13) was found in the cytosolic fraction of rat liver and various other tissues. The extent of the inhibitory effect was dependent on the concentration of the cytosolic protein. The Acid CEH inhibitor was heat-labile, non-dialyzable, and its inhibitory activity significantly decreased by trypsin or chymotrypsin digestion, but not by lipase digestion. The inhibitor had no effect on the activity of cathepsin D, beta-glucuronidase and acid phosphatase, which are other enzymes found in lysosomes. The present findings suggest that the inhibitor may be involved in the regulation of the hydrolysis of cholesteryl esters in lipoproteins that have been transferred into the liver.
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PMID:Characterization of a cytosolic protein inhibiting lysosomal acid cholesteryl ester hydrolase. 650 18

Studies have compared "total", HMW kininogen and leukokininogen levels in human, rabbit and rat plasma using trypsin, glass powder and cathepsin D as kininogenases or activators of kininogenases. Rat plasma was found to have about 10 fold more leukokininogen than the other plasmas assayed. When trypsin was used to estimate total kininogen, rat plasma liberated maximal amounts of kinin only in the presence of high concentrations of trypsin (1 mg/ml incubation mixture). In addition, it was found that trypsin in these concentrations liberated from rat plasma both bradykinin and a previously unidentified kinin which we have termed "T-kinin". The results overall indicate that in the case of rat and rabbit plasma, currently used methods for estimations of total kininogen may not be accurate. T-kinin may represent a leukokininogen or a hitherto undescribed kininogen.
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PMID:Kininogen substrates for trypsin and cathepsin D in human, rabbit and rat plasmas. 655 Jul 7

This study was undertaken to confirm our previous preliminary observation that hog pancreas kallikrein (EC 3.4.21.35) directly liberated an angiotensin-like substance from human plasma protein Cohn fraction IV-4 at an acidic pH of 4.0-5.0. First, the possibility of proangiotensin or des-Asp1-angiotensin being the pressor substance was ruled out by t.l.c. Secondly, the pressor substance was purified by Sephadex G-25 and Bio-Gel P-2 gel filtration, and finally by high-performance liquid chromatography. The amino acid composition of the isolated pressor substance (residues/mol) was: Asp, 1.03; Val, 1.03; Ile, 1.00; Tyr, 0.69; Phe, 1.04; His, 0.91; Arg, 0.86; Pro, 0.86. This composition was identical with that of angiotensin. Since the reaction mixture was not contaminated with common proteolytic enzymes, such as trypsin, chymotrypsin, renin, cathepsin D and proangiotensin-converting enzyme, and other enzymes activated by kallikrein, it is clear that hog kallikrein directly produces angiotensin in vitro.
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PMID:Confirmation of direct angiotensin formation by kallikrein. 655 43


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