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)

Peptides derived from enzymatic digestions (cathepsin D and trypsin) were characterized and amino acid sequences determined by using their LC/MS spectra. A Frit-FAB interface that produces extensive peptide fragmentation and permits amino acid sequencing at the low picomole level is described for a model antigen, Staphylococcus aureus nuclease (Nase), and an enzyme of unknown structure, yeast aminopeptidase B. The amino acid sequences of peptides derived from digestion of Nase with cathepsin D (a relatively nonspecific endoprotease) were readily deduced and have provided insights into the nature of antigen processing. Frit-FAB LC/MS spectra of the Nase peptides contained a sufficient number of fragment ions to conclusively identify peptides with a mass below 2000 Da. Capillary LC/MS provided a means for the separation and identification of these enzymatically derived peptides in a fraction of the time that would have been required by gas-phase Edman sequence analysis. The optimized Frit-FAB experiment was consequently evaluated for the partial characterization of aminopeptidase B recently purified to homogeneity from Saccharomyces cerevisiae. Sequence-specific ions observed in the Frit-FAB mass spectra of these tryptic peptides were identical with those commonly observed in high-energy collision-induced dissociation (CID) spectra and included side-chain fragment ions that differentiated leucine from isoleucine. These fragment ions were used to deduce entire amino acid sequences for several of the tryptic peptides.
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PMID:Optimization of the fragmentation in a frit-fast atom bombardment ion source for the sequencing of peptides at the picomole level. 175 Jun 99

1. P. yoelli nigeriensis has an acid endoprotease (cathepsin D) and an endoarylamidase. 2. The acid endoprotease is specific towards haemogloblin. It is found in 2 molecular forms, of molecular weight 100,000 and 50,000. It is inhibited by hematin and pepsatin. 3. In mouse normal red blood cells we find an acid protease having physico-chemical properties similar to those of the enzyme present in P. yoelii nigeriensis extracts, except as regards the pHi. 4. In parasite extracts there exists an enzyme active on the synthesis substrate N-acetyl alanine 4 nitro anilide. The main properties of this enzyme have been determined. 5. This enzyme must be also involved in the mechanism of haemoglobin degradation.
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PMID:Endoprotease in Plasmodium yoelii nigeriensis. 634 Sep 50

We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells.
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PMID:Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer. 758 35

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.
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PMID:Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer? 820 35

A functional approach of gene cloning was applied to HeLa cells in an attempt to isolate positive mediators of programmed cell death. The approach was based on random inactivation of genes by transfections with antisense cDNA expression libraries, followed by the selection of cells that survived in the presence of the external apoptotic stimulus. An antisense cDNA fragment identical to human cathepsin D aspartic protease was rescued by this positive selection. The high cathepsin D antisense RNA levels protected the HeLa cells from interferon-gamma- and Fas/APO-1-induced death. Pepstatin A, an inhibitor of cathepsin D, suppressed cell death in these systems and interfered with the TNF-alpha-induced programmed cell death of U937 cells as well. During cell death, expression of cathepsin D was elevated and processing of the protein was affected, which resulted in high steady-state levels of an intermediate, proteolytically active, single chain form of this protease. Overexpression of cathepsin D by ectopic expression induced cell death in the absence of any external stimulus. Altogether, these results suggest that this well-known endoprotease plays an active role in cytokine-induced programmed cell death, thus adding cathepsin D to the growing list of proteases that function as positive mediators of apoptosis.
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PMID:Cathepsin D protease mediates programmed cell death induced by interferon-gamma, Fas/APO-1 and TNF-alpha. 867 Aug 91

Since the presence of precursors (pro-forms) of the aspartyl endoprotease, cathepsin D, appears to be linked with tumor progression, their presence was examined in sera and tumor tissues of ovarian cancer patients. The role of cathepsin D pro-forms was further assessed in the dysregulated proliferation and chemoresistance observed in advanced ovarian cancer. Cathepsin D was isolated from sera of ovarian cancer patients (n = 20) and normal volunteers (n = 11), as well as from solubilized normal ovarian epithelium (n = 8) and ovarian epithelial tumor tissue (n = 12). The specific molecular forms of cathepsin D were analyzed in these samples by Western immunoblot. Multiple circulating molecular weight forms of cathepsin D were identified in ovarian cancer patients ranging from 24 to 60 kDa, while in normal controls, a major band was observed at 34 kDa in all samples and minor bands corresponding to 27 and 48 kDa were detected in approximately half of the controls. To assess its consequences on ovarian cancer, the 52-kDa protein was immunoprecipitated from culture medium of an exponentially growing ovarian tumor cell line and was further purified by reverse-phase high-pressure liquid chromatography. Its effect on proliferation was assayed by determining cell doubling times and their chemosensitivity was measured in a standard cytotoxicity assay using cisplatin. In addition, decapeptides corresponding to the pro-portion of cathepsin D were analyzed in parallel. Procathepsin D and one decapeptide, peptide 2, as well as IGF-II (as a known positive) increased cell proliferation, with doubling times of 28.4, 28.8, and 30.3 h, respectively, versus untreated UL-1 cells (36.4 h). Procathepsin D treatment of UL-1 tumor cells significantly increased the cisplatin LD(50) (74.9 microgram/ml) over untreated (33.9 microgram/ml) as well as IGF-II-treated (38.8 microgram/ml) cells. Peptide 2 also showed a significant increase in LD(50) (69.5 microgram/ml) compared to untreated and peptide 1-treated cells (37.1 microgram/ml). There are several unique forms of cathepsin D expressed and accumulated by ovarian tumors and these forms are detectable in the sera of those with ovarian cancer. The presence of these procathepsin D can increase the proliferation of these tumor cells, while decreasing their sensitivity to chemotherapeutic agents. While procathepsin D and IGF-II both enhance proliferation, only procathepsin D (and peptide 2) appears to modulate chemosensitivity, suggesting a separate receptor or pathway for this consequence.
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PMID:Modulation of proliferation and chemosensitivity by procathepsin D and its peptides in ovarian cancer. 1041 29

Digestive endoprotease activities of the rice water weevil, Lissorhoptrus brevirostris Suffrian (Coleoptera: Curculionidae), were characterized based on the ability of gut extracts to hydrolyze specific synthetic substrates, optimal pH, and hydrolysis sensitivity to protease inhibitors. Larvae of this species were found to use a complex proteolytic system that includes cathepsin D-, cathepsin B-, trypsin-, and chymotrypsin-like activities. Trypsin-like activity was evenly distributed among the anterior, middle, and posterior portions of the gut, whereas cathepsin B- and cathepsin D-like activities were mainly located in the anterior and middle sections, and the chymotrypsin-like activity was highest in the middle and posterior sections. Gelatin-containing native-PAGE gels indicated the presence of several aspartyl, cysteine, and serine protease forms and confirmed the spatial organization of the proteolytic digestive process.
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PMID:Proteolytic gut activities in the rice water weevil, Lissorhoptrus brevirostris Suffrian (Coleoptera: Curculionidae). 1270 Nov 11

Prohormones mature to biologically active peptide hormones through posttranslational modifications, which include endoproteolytic cleavages. Cleavages at mono- and dibasic sites are well characterized, and several of the responsible prohormone convertases have been identified. There is, however, evidence that endoproteolytic maturation occurs also at other sites. Among these, post-Phe cleavage occurs in the maturation of chicken progastrin, where the processing to gastrin-30 has been examined in detail. In this study we have characterized an endoprotease of the aspartic acid protease family in chicken and human tissue capable of cleaving at the Phe site. Enzymatic activity was monitored by radioimmunoassays using antibodies specific for the N- and C-termini exposed after cleavage. Analysis showed that only pepstatin, a specific inhibitor of aspartic proteases, inhibited the enzyme. The pH optimum of the enzyme ranged from pH 2 to pH 5. Amino acid substitution from Phe to Ala in the substrate completely abolished enzyme activity. The endoproteolytic activity was identified in chicken antrum and pectoral muscle as well as human cardiac and prostate extracts, suggesting that the enzyme has widespread biological functions. Experiments using recombinant cathepsin D and E indicated that neither is responsible for the endoproteolytic cleavage of chicken progastrin at post-Phe bonds.
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PMID:Processing of chicken progastrin at post-Phe bonds by an aspartyl protease. 1575 91

The protein pattern of healthy human eccrine sweat was investigated and 10 major proteins were detected from which apolipoprotein D, lipophilin B, and cathepsin D (CatD) were identified for the first time in human eccrine sweat. We focused our studies on the function of the aspartate protease CatD in sweat. In vitro digestion experiments using a specific fluorescent CatD substrate showed that CatD is enzymatically active in human sweat. To identify potential substrates of CatD in human eccrine sweat LL-37 and DCD-1L, two antimicrobial peptides present in sweat, were digested in vitro with purified CatD. LL-37 was not significantly digested by CatD, whereas DCD-1L was cleaved between Leu(44) and Asp(45) and between Leu(29) and Glu(30) almost completely. The DCD-1L-derived peptides generated in vitro by CatD were also found in vivo in human sweat as determined by surface-enhanced laser desorption/ionization (SELDI) mass spectrometry. Furthermore, besides the CatD-processed peptides we identified additionally DCD-1L-derived peptides that are generated upon cleavage with a 1,10-phenanthroline-sensitive carboxypeptidase and an endoprotease. Taken together, proteolytic processing generates 12 DCD-1L-derived peptides. To elucidate the functional significance of postsecretory processing the antimicrobial activity of three CatD-processed DCD-1L peptides was tested. Whereas two of these peptides showed no activity against Gram-positive and Gram-negative bacteria, one DCD-1L-derived peptide showed an even higher activity against Escherichia coli than DCD-1L. Functional analysis indicated that proteolytic processing of DCD-1L by CatD in human sweat modulates the innate immune defense of human skin.
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PMID:Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L. 1635 54

According to the protein-only hypothesis of prion propagation, prions are composed principally of PrP(Sc), an abnormal conformational isoform of the prion protein, which, like its normal cellular precursor (PrP(C)), has a GPI (glycosylphosphatidylinositol) anchor at the C-terminus. To date, elucidating the role of this anchor on the infectivity of prion preparations has not been possible because of the resistance of PrP(Sc) to the activity of PI-PLC (phosphoinositide-specific phospholipase C), an enzyme which removes the GPI moiety from PrP(C). Removal of the GPI anchor from PrP(Sc) requires denaturation before treatment with PI-PLC, a process that also abolishes infectivity. To circumvent this problem, we have removed the GPI anchor from PrP(Sc) in RML (Rocky Mountain Laboratory)-prion-infected murine brain homogenate using the aspartic endoprotease cathepsin D. This enzyme eliminates a short sequence at the C-terminal end of PrP to which the GPI anchor is attached. We found that this modification has no effect (i) on an in vitro amplification model of PrP(Sc), (ii) on the prion titre as determined by a highly sensitive N2a-cell based bioassay, or (iii) in a mouse bioassay. These results show that the GPI anchor has little or no role in either the propagation of PrP(Sc) or on prion infectivity.
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PMID:Removal of the glycosylphosphatidylinositol anchor from PrP(Sc) by cathepsin D does not reduce prion infectivity. 1644 Dec 39


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