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 role of insulin as a possible mediator of the beta-adrenergic agonist stimulation of muscle growth was investigated. To exclude possible action of the beta-agonist on the pancreatic release of insulin, diabetes was induced in rats by a streptozotocin injection (100 mg/kg). Insulin levels were almost not detectable in these rats. Feeding either normal diet or diet containing the beta-adrenergic agonist clenbuterol (10 parts/million) did not alter plasma insulin concentrations. The effects of clenbuterol on muscle and weight gain were determined in diabetic rats given daily insulin replacement (D + I) and fed either a normal diet or clenbuterol-treated diet. Clenbuterol, fed for 1 wk, increased the wet weight of the gastrocnemius, soleus, and extensor digitorum longus muscles (15-23%) in both normal and D + I rats. Although clenbuterol increased body weight gain, it did not alter feed consumption and, therefore, feed efficiency (g gain/g food) was improved. Activities of cathepsin B and N-acetyl-beta-glucosaminidase, but not cathepsin D, were elevated in the soleus muscles of clenbuterol-treated rats. The clenbuterol-induced increase in muscle growth in the insulin-replaced diabetic rats indicated that this beta-adrenergic agonist effect was not mediated by an alteration of circulating levels of insulin, secondary to beta-agonist action on pancreatic insulin release.
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PMID:Clenbuterol-induced muscle growth: investigation of possible mediation by insulin. 331 Jun 57

Hemolysates of human erythrocytes contain a highly specific insulin- and glucagon-degrading activity which is comparable to the so-called insulin- and glucagon-degrading proteinase (IGP, EC 3.4.23.5) found in other tissues. Glucagon degradation is inhibited by its cleavage products. Insulin, proinsulin and also cleavage products of insulin are effective inhibitors of glucagon degradation. The isolated insulin A- and B-chains are also capable of inhibiting the splitting of glucagon, but a higher concentrations. On the other hand, glucagon influences insulin degradation. Naturally occurring substances within commercially available human serum albumin have remarkable inhibitory effects on the glucagon degradation.
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PMID:Glucagon- and insulin degradation by hemolysate of human erythrocytes. 332 71

The pattern of islet lysosomal enzyme activities, islet insulin concentration and the plasma levels of insulin and glucose were studied in freely fed mice after the in vivo administration of diazoxide in doses known to induce crinophagy in islet beta-cells. After diazoxide treatment at time 0 and at 18 hr, the plasma glucose levels at 20 hr were markedly enhanced from 6.6 +/- 0.2 mmol/l (controls) to 27.2 +/- 2.7 mmol/l (diazoxide). Inhibition of insulin secretion by diazoxide was reflected in the insulinogenic index, which was reduced by approximately 40% (p less than 0.01) in the diazoxide-treated animals, who also displayed an increased concentration of islet insulin (+50%; p less than 0.01). Moreover, we found that the activities of certain lysosomal enzymes in islet tissue were markedly increased following diazoxide treatment. Thus the activities of the acid phosphatase, (+57%; p less than 0.02) the hexosaminidase N-acetyl-beta-D-glucosaminidase, (+52%; p less than 0.001), and the carboxyl proteinase cathepsin D (+41%; p less than 0.001), were all enhanced after diazoxide, whereas the activity of another lysosomal enzyme, the glycogen hydrolysing acid amyloglucosidase, was not altered by diazoxide treatment. The present data thus indicate that the morphological observation of diazoxide-induced crinophagy in pancreatic beta-cells has a biochemical correlate in enhanced levels of certain islet lysosomal enzyme activities known to participate in degradative processes. The results also suggest that islet lysosomal enzyme activities and/or lysosome populations can be modulated by a relative independence from each other.
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PMID:Biochemical determination of islet lysosomal enzyme activities following crinophagy-stimulating treatment with diazoxide in mice. 332 35

Lysosomal enzyme activities in pancreatic islets of obese hyperglycemic ob/ob mice aged 3 to 6 months were investigated and compared with those of normal lean NMRI mice of the same age. It was observed that the glycogenolytic glucose-producing hydrolase acid amyloglucosidase displayed a fivefold higher activity in the islets of obese mice than in the islets of normal NMRI mice. However, other islet lysosomal enzyme activities measured, such as N-acetyl-beta-D-glucosaminidase and beta-glucuronidase, were of the same magnitude in both obese and lean mice. A starvation period of 24 hours induced a significant depression of islet acid amyloglucosidase activity in obese as well as lean mice, whereas the activities of N-acetyl-beta-D-glucosaminidase and beta-glucuronidase were unaffected. Further, the activities of other types of islet lysosomal enzymes, such as acid phosphatase and cathepsin D, were also measured in obese mice. These activities were not found to be affected by the actual fasting period. A good correlation (r = 0.815; P less than 0.01) was observed between islet acid amyloglucosidase activity and plasma insulin concentrations in obese mice, whereas no such relationship was apparent with regard to other islet lysosomal enzyme activities recorded. Acid amyloglucosidase activity in liver tissue of the obese mouse was about 30 times lower than that of islet tissue. Further, the activity of liver amyloglucosidase was of the same order of magnitude in obese and lean mice. Similarly, other lysosomal enzyme activities in the liver of obese and lean mice were not strikingly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysosomal enzyme activities in pancreatic islets from normal and obese hyperglycemic mice. 391 27

A new aspartic proteinase was isolated from porcine intestine mucosa by affinity chromatography on pepstatin-Sepharose 4B and gel filtration on Sephadex G-100. The enzyme was purified 1600-fold and appeared homogeneous upon polyacrylamide gel electrophoresis. The proteinase has a Mr 60 000 +/- 4000 Da. During sodium dodecyl sulfate polyacrylamide gel electrophoresis the enzyme produced a single protein band (Mr 30 000 +/- 3000 Da). Isoelectric focusing revealed that the enzyme has several multiple forms (pI 6.9, 7.5, 8,0). The enzyme is a glycoprotein containing 5.9% of carbohydrates; the mannose to galactose ratio is 1:3. The amino acid composition of the enzyme was studied. The proteinase splits an oxidized insulin B-chain and synthetic substrates. The pH optimum is 3.2. The enzyme is immunologically identical to porcine spleen cathepsin D.
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PMID:[Proteinases of small intestine enterocytes of swine. Purification and properties of aspartyl proteinase similar to cathepsin D]. 393 2

Cathepsin D was purified from the lactating rabbit mammary gland by a rapid procedure, which included fractionation with (NH4)2SO4, acid precipitation, double affinity chromatography on pepstatin-Sepharose 4B and gel filtration on Sephadex G-100, resulting in approximately 360-fold purification of the enzyme over the homogenate and approximately 16% recovery. After isoelectric focusing, the enzyme dissociated into four (pI 5.8, 6.3, 6.5 and 7.2) multiple forms, but appeared homogeneous on polyacrylamide gel electrophoresis. Cathepsin D has a Mr of 45 kDa as determined by Sephadex G-100 column chromatography. On sodium dodecylsulfate/polyacrylamide gel electrophoresis the enzyme gave a single protein band, corresponding to Mr of 45 kDa. The amino acid composition of the enzyme is similar to that of cathepsins D from other tissues. A single N-terminal amino acid was glycine. Cathepsin D contains 6.4% carbohydrates consisting of mannose, galactose, fucose and glucosamine at a ratio of 3:9:2:2. Cathepsin D is inhibited by pepstatin with Ki of 2.5 X 10(-9) M and irreversibly by N-diazoacetyl-N'-2.4-dinitrophenyl-ethylene diamine. The enzyme hydrolyzes bovine hemoglobin with the maximal activity at pH 3.0 with Km = 10(-5) M and HLeu-Ser-Phe(NO2)-Nle-Ala-Leu-OMe with Km = 4 X 10(-5) M and Rcat = 0.95 s-1. The major cleavage sites were Leu15-Tyr16, Phe24-Phe25 and Phe25-Tyr26 during hydrolysis of the oxidized insulin B-chain by cathepsin D.
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PMID:[Purification and properties of cathepsin D from the mammary glands of lactating rabbits]. 400 22

Proteolytic enzymes have been studied in extracts of human articular cartilage by the use of micromethods. The digestion of hemoglobin at pH 3.2 and of cartilage proteoglycan at pH 5 was shown to be due chiefly to cathepsin D. Cathepsin D was purified 900-fold from human patellar cartilage. Its identity was established by its specific cleavage of the B chain of insulin. At least six multiple forms of cathepsin D are present in cartilage; these corresponded to bovine forms 4-9. Cathepsin D had no action on proteins at pH 7.4. However, cartilage extracts digested proteoglycan, casein, and histone at this pH. The proteolytic activities against these three substrates were purified about 170-, 160-, and 70-fold, respectively. Each activity appeared in multiple forms on DEAE-Sephadex chromatography. The three activities appear to be different since cysteine inhibited casein digestion, aurothiomalate inhibited histone digestion, and neither inhibited proteoglycan digestion. Tests with a wide range of inhibitors and activators suggest that these three activities differ from other neutral proteases described in the literature.
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PMID:Neutral proteases and cathepsin D in human articular cartilage. 427 25

Pancreatectomy as well as thyroparathyroidectomy resulted in the quick disappearance of a serum factor (stimulating cathepsin D release from lysosomes in vitro) from the rat or mouse blood. Extirpation of other organs such as duodenum, stomach, spleen, kidney, submaxillary gland, testis, adrenal gland or hypophysis, showed no effect on the serum factor level. Glucagon (but not insulin or thyroxine) given to the pancreatectomized animals restored the serum factor level in a dose-dependent manner. The serum factor-like activity was detected only in the parathyroids (but not thyroid), and the release of activity from parathyroid-slices was stimulated by glucagon, suggesting that the parathyroid may produce and/or secrete the serum factor under the influence of glucagon.
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PMID:Tissue producing the serum factor stimulating the release of cathepsin D from lysosomes in vitro. 614 Oct 30

The specific activity of cardiac cathepsin B is significantly decreased by starvation and corticosteroid treatment in vivo, and by exposure of the heart in vitro to insulin, hydrocortisone and cycloheximide. Increases in cathepsin B activity occur following isoproterenol-induced cardiac damage in vivo and exposure in vitro to sucrose. Cathepsin B activity in heart is not changed during normal aging or in thyrotoxicosis. These responses are different from simultaneous changes in cardiac cathepsin D activity in several instances (starvation, corticosteroid treatment, aging and thyrotoxicosis). In the past, measurements of cathepsin D activity in heart have sometimes been considered to be representative of lysosomal proteinase activity in general and used as an index of cardiac lysosomal proteolytic capacity. The present results suggest that changes in cathepsin D do not necessarily reflect alterations in other lysosomal proteinases and may not serve as a valid indicator of overall lysosomal proteolytic capacity under all conditions.
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PMID:Changes in cardiac cathepsin B activity in response to interventions that alter heart size or protein metabolism: comparison with cathepsin D. 623 80

The degradation of [125I]iodoinsulin in anglerfish islet tissue was studied in a trichloroacetic acid solubilization assay system. The pH optima for insulin breakdown by acidic and neutral enzymes were determined in fish islets and compared with mammalian tissues (rat liver, pancreas, and islets of Langerhans). Two major insulinolytic activities of anglerfish islet tissue were partially characterized: 1) An acidic (pH 3.5) activity showing marked sensitivity to pepstatin, some sensitivity to antipain, leupeptin, phenylmethanesulfonyl fluoride (PMSF), and thiol proteinase inhibitors, but no inhibition by EDTA; and 2) a neutral (pH 7.3) activity showing marked sensitivity to thiol proteinase inhibitors, sensitivity to antipain and leupeptin, but no sensitivity to PMSF, EDTA, or pepstatin. Glucagonolytic activities were also observed at the same acidic and neutral pH optima. Following cell fractionation of anglerfish islet homogenates, acidic (pH 3.5) insulinolytic activities were distributed with the lysosome-rich, microsome, and cytosol fractions, whereas neutral (pH 7.3) activities were found chiefly in cytosol and microsomes. Little or no insulinolysis was observed in secretory granule fractions. The data suggest that insulin is degraded in islet tissue by at least two enzyme systems. Lysosomal insulinolysis was due principally to cathepsin D-like activity. Neutral insulinolysis, partially characterized in the cytosol fraction, was due to thiol proteinase activity. The activity profile indicates that islet tissue resembles other insulin-responsive tissues in its subcellular distribution of insulin-degrading activities. The cellular heterogeneity of islet tissue, and the presence of high concentrations of endogenous islet hormones require further efforts at purification before insulinolytic enzymes are fully characterized in this tissue.
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PMID:Subcellular localization and preliminary characterization of islet hormone-degrading activities in anglerfish islet tissue. 634 Nov 66


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