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)

Two acid proteases, one hydrolysing hemoglobin and the other hydrolysing benzoyl arginine naphthyamide (BANA), were separated and partially purified from human skin buffer extract. The acid protease hydrolysing hemoglobin was purified about 190 fold by Sephadex G-100 gel filtration and DEAE-cellulose chromatography. It hydrolysed hemoglobin at pH 3.5, casein at pH 5.8 and skin protein substrate at pH 6.0. It did not markedly hydrolyse synthetic protease substrates. The molecular size of this protease was 38000. The protease was insensitive to common protease modifiers and closely resembles cathepsin D purified from other organs. The BANA-hydrolysing acid protease was purified about 760 fold by Sephadex G-100 gel filtration and affinity chromatography on organomercurial Sepharose 4B gel. It preferentially hydrolysed BAEE, BANA and BAA with an optimum at pH 5.8. The hydrolysis of BAPA, LeuNA and protein substrates was very low. This acid protease was found to be highly dependent on reducing agents, as DTT, and chelating agents, as EDTA, and was inhibited by pCMB and TLCK. The molecular size of the enzyme was 28000. This protease closely resembles cathepsin B1 purified from other organs. Human skin was also shown to contain a low activity of benzoyl arginine amide (BAA) hydrolysing acid protease with a molecular size of about 50000 and resembling cathepsin B2. Human skin contained an inhibitor with a molecular size of about 13000 against human skin cathepsin B1. This inhibitor did not inhibit trypsin, chymotrypsin or skin proteases other than cathepsin B1.
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PMID:Human skin proteases. Separation and characterization of two acid proteases resembling cathepsin B1 and cathepsin D and of an inhibitor of cathepsin B1. 0 17

Psoriatic scale proteases were found to be extracted effectively in salt solution (1 mol/l) containing Triton X-100 (5 g/l). The extraction in dilute buffer or sucrose yielded low activities. The acid (0.25 N H2SO4) and KSCN (2 mol/l) solutions effectively extracted plasminogen activator. Fibrinolysin was most active in salt (1 mol/l KCl) and in KSCN (2 mol/l) extracts. Psoriatic scale proteases were fractionated by Sephadex G-100 gel filtration and further by DEAE cellulose chromatography. Five different enzyme preparations were obtained. The first preparation, resembling cathepsin D, effectively hydrolysed hemoglobin at pH 3.5 and casein at pH 5.8 and was insensitive to protease modifiers. The second preparation effectively hydrolysed trypsin substrates (AGLME, TAME, BAEE and BANA) and also histone and casein at pH 7.2 and was inhibited by protease inhibitors, TLCK and E-600. The third preparation hydrolysed histone and casein at pH 10.2 and was effectively inhibited by E-600 and partially by protease inhibitors and TPCK. The fourth preparation, resembling cathepsin B1, hydrolysed BANA and BAEE at pH 5.8 and was activated by SH-reagents and EDTA. The fifth enzyme preparation hydrolysed ATEE and was inhibited by E-600 and TPCK. Plasminogen activator was found mainly in the second enzyme preparation and fibrinolysin activity in the third and fifth enzyme preparations. The second, third and fifth enzyme preparations were different from the enzymes found in healthy human skin. The proteases of psoriatic scale resemble those of tissue and cell cultures undergoing rapid cell division. The possible role of proteases in the increased cell division in psoriasis plaque is discussed.
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PMID:Human skin proteases. Fractionation of psoriasis scale proteases and separation of a plasminogen activator and a histone hydrolysing protease. 0 31

The lysate of the glycogen-induced macrophages in rat peritoneal exudate was fractionated by centrifugation and extraction into a water extract, 1 M KCl extract and residue fractions. Approximately 50% of the neutral protease activity toward casein in the lysate was recovered in the KCl extract fraction, which was practically devoid of acid protease, cathepsin D. The pH optimum of the neutral protease toward casein and urea-denatured hemoglobin was pH 8.5. The activity was inhibited strongly by DFP or chymostatin and only partially by HgCl2 or PCMB. Addition of a salt to the reaction medium caused enhancement of the activity with an optimum concentration of 0.25 M: KCl, KBr, KI, NaCl, NaBr, NaI, and MgCl2 were all almost equally effective. When the enzyme preparation was filtered through a column of Sephadex G-75 gel in the presence of 1 M KCl, a larger molecular weight fraction at the void volume was obtained in addition to a smaller molecular weight fraction showing a caseinolytic activity insensitive to KCl concentration. The former was found to have a specific inhibitory effect on the latter activity.
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PMID:The occurence of a neutral protease and its inhibitor in rat peritoneal macrophages. 1 54

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

A chymotrypsin-like esterase was purified from beef lung. This lysosomal enzyme, not previously characterized, seemed to be composed of two or more forms with molecular weights of about 52 000. It hydrolysed N-benzoyl-DL-phenylalanine beta-naphthol ester at acid and neutral pH; it polymerized L-phenylalanine methyl ester(Phe-OMe) at neutral pH; and it transferred the Phe-residue from Phe-OMe to hydroxylamine at neutral pH. Phenylmethanesulfonyl fluoride, an inhibitor of hydrolytic enzymes with serine in their catalytic site, inhibited this enzyme, but pepstatin, the cathepsin D (EC 3.4.4.23) inhibitor, did not. Sulfhydryl reagents were not required for activity. Macrophages, especially pulmonary alveolar macrophages, were a rich source of this esterase, so it is likely that the enzyme purified from lung came from its macrophages. The esterase hydrolysed and transferred monoamino acid esters, especially those of the aromatic type. Cathepsin C, the dipeptidyl peptide hydrolase (EC 3.4.14.1), acted only on dipeptide esters and amides. Pancreatic chymotrypsin acted on both monoamino acid and dipeptide esters. The chymotrypsin-like esterase did not hydrolyse hemoglobin, casein, or plasma albumin. Thus its proteolytic activity, if present, must be limited to specific substrates, as yet unknown.
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PMID:Macrophage esterase: identification, purification and properties of a chymotrypsin-like esterase from lung that hydrolyses and transfers nonpolar amino acid esters. 24 Apr 26

In previous studies, we found a significantly higher (100% or more) content of cathepsin D in the aging brain. In the present study, we determined activity of Ca2(+)-activated neutral protease requiring millimolar Ca2+ (calpain II, CANP II) and amount of its endogenous inhibitor, calpastatin, in extracts of various brain regions of 3-month-old and 24-month-old male Fischer-344 rats. Calpain II was separated from calpastatin in a single step (chromatography) and its activity was tested using as substrates [methyl-14C]alpha-casein, the cytoskeletal proteins desmin and actin, and a mixture of neurofilament triplet proteins and glial fibrillary acidic proteins (GFAP). We found no changes in calpain II activity in pons-medulla and spinal cord, but significant increases were detected in cortex (72%) and striatum (63%) of the 24-month-old rats using [methyl-14C]alpha-casein as substrate. The profile of desmin and actin breakdown showed regional variations somewhat different from those of [methyl-14C]alpha-casein. With desmin, the greatest increases with age were in the striatum (82%) and hypothalamus (46%), but there were no alterations in cortex, cerebellum, and pons-medulla. With actin, slightly enhanced activity in cortex and cerebellum was noticeable. Calpastatin content in brain regions was also increased, with the regional pattern of increase fairly similar to the pattern of enzyme activity increase. The causes and the physiological consequences of increased calpain and calpastatin content in the aged brain are being investigated. That changes with age are somewhat different with the various brain protein substrates indicates that some of the properties of the enzyme also undergo alteration with age.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calpain II activity and calpastatin content in brain regions of 3- and 24-month-old rats. 236 29

Casein-induced amyloidosis in hamsters was found to be of the AA-type, as shown by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and amino acid analysis of the major low-molecular weight component of the amyloid fibrils. Levels of serum amyloid A (SAA) and the activities of cathepsin D, beta-N-glucosaminidase, serine esterase, lactate dehydrogenase (LDH) and gamma glutamyl transpeptidase (GGT) were measured in the blood plasma during induction of amyloidosis. During the pre-amyloid phase an increase was observed in all these parameters. During the deposition of amyloid, an increase was observed in the activities of the lysosomal enzymes cathepsin D and beta-N-glucosaminidase, which was significantly correlated with amyloid deposition. Serine esterase activities did not show any relationship to amyloid deposition. LDH and GGT activities were normal in the amyloid phase. SAA levels were lower during amyloid deposition than during the pre-amyloid phase. These findings indicate that a specific release of lysosomal contents from mononuclear phagocytic cells is involved in the pathogenesis of AA-amyloidosis. Amyloid deposition may be the result of: (i) extrusion of intralysosomal protein AA or pre-amyloid, followed by extracellular formation of amyloid fibrils; (ii) secretion of lysosomal enzymes, followed by extracellular cleavage of SAA and subsequent aggregation of protein AA with other components.
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PMID:Activities of lysosomal enzymes and levels of serum amyloid A (SAA) in blood plasma of hamsters during casein induction of AA-amyloidosis. 286 Sep 18

AA-amyloidosis was induced in hamsters receiving amyloid-enhancing factor (AEF) by daily subcutaneous injection with either an aged casein solution or casein supplemented with lipopolysaccharide (LPS). Both amyloid inducers gave similar results with respect to amyloid development in spleen, liver and kidneys and to serum amyloid A (SAA) concentrations and plasma cathepsin D activities. AEF was isolated from amyloid-containing tissue by the method described by Hol et al. (1985), and amyloid-enhancing material was also extracted from isolated hamster amyloid fibrils by intensive sonification. This fibril-derived amyloid-enhancing material lacked typical green birefringence after staining with Congo red and appeared as amorphous material on electron microscopy. AEF shortened the pre-amyloid phase for splenic and hepatic amyloid development and also the subsequent interval before renal amyloid deposition. This indicates that endogenous AEF, unlike passively transferred preformed AEF, is not distributed throughout the body and is probably generated at the site of amyloid deposition. Moreover, these results suggest that amyloid deposition in the kidneys, like that in the spleen and liver, involves an AEF-dependent pathway. Thus redistribution of amyloid is probably not an important cause of renal amyloid involvement. In addition to the reduction in the lag phase for splenic and hepatic amyloid deposition, AEF also speeds the changes in SAA concentration and plasma cathepsin D activity. This indicates that AEF accelerates rather than eliminates the pre-amyloid phase.
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PMID:Amyloid-enhancing factor (AEF) in the pathogenesis of AA-amyloidosis in the hamster. 287 82

Three peaks of proteinases were observed with hemoglobin, bovine serum albumin and casein as substrates at the pH of 3.5, 6.5 and 8.5, in prenatal human cerebral cortex. Cathepsin D (EC 3.4.23.5) was the most prominent, with hemoglobin as the preferred substrate. The enzyme was partially purified by Concanavalin A - Sepharose affinity chromatography and the nature of the active site was assessed with proteinase inhibitors. Inhibitor studies showed that similar to pepstatin A, benzethonium chloride was also strongly inhibitory to the enzyme. The distribution of cathepsin D, a neuronal marker, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37), a oligodendroglial marker in foetal brain regions with increasing gestation revealed that neurogenesis and gliogenesis occur concomitantly from earlier periods of gestation. Glial marker acquisition was particularly high in medulla and in spinal cord between 20 and 25 weeks of gestation.
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PMID:Cathepsin D and 2',3'-cyclic nucleotide 3'-phosphohydrolase in developing human foetal brain. 321 74

Crude homogenates of the soil nematode Caenorhabditis elegans exhibit strong proteolytic activity at acid pH. Several kinds of enzyme account for much of this activity: cathepsin D, a carboxyl protease which is inhibited by pepstatin and optimally active toward hemoglobin at pH 3; at least two isoelectrically distinct thiol proteases (cathepsins Ce1 and Ce2) which are inhibited by leupeptin and optimally active toward Z-Phe-Arg-7-amino-4-methylcoumarin amide at pH 5; and a thiol-independent leupeptin-insensitive protease (cathepsin Ce3) with optimal activity toward casein at pH 5.5. Cathepsin D is quantitatively most significant for digestion of macromolecular substrates in vitro, since proteolysis is inhibited greater than 95% by pepstatin. Cathepsin D and the leupeptin-sensitive proteases act synergistically, but the relative contribution of the leupeptin-sensitive proteases depends upon the protein substrate.
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PMID:Proteases of the nematode Caenorhabditis elegans. 327 41


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