Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The number of rat liver autophagic vacuoles (AVs) was increased by separate injection of three different inhibitors--vinblastine, leupeptin, and chloroquine--of lysosomal protein degradation. The different mechanisms of action of the agents correlated to the ultrastructure of the AVs. Accumulation of the base chloroquine with ensuing influx of water into AVs caused a significant swelling. The leupeptin-induced AVs were processed into residual-body-like structures within a few hours of exposure in line with the presence of a leupeptinase in liver tissue. Vinblastine was the most efficient agent in increasing the occurrence of AVs. The effect of vinblastine lasted for the entire study period (36 hr) with continuous formation of nascent AVs. In addition, vinblastine caused the appearance of a subpopulation of AVs laden with VLDL particles. The term crinosomes was suggested for these hybrid organelles, since they seemed to evolve by fusion between secretory granules and lysosomes. In addition to sequestered cell organelles, the AVs harbored cytosolic enzyme activities (LDH and aldolase). Leupeptin was the only agent that caused a decrease in cathepsin B and L activities. Similarly, leupeptin impeded protein breakdown in isolated AVs, whereas vinblastine and chloroquine evoked an increase. In vivo, chloroquine and vinblastine block protein degradation. The reason for this discrepancy is probably that during in vivo exposure the substrate (cytoplasmic proteins) is built up in the AVs because degradation is retarded. Upon isolation of the AVs the inhibitor block is released, and proteolysis proceeds at enhanced rates over control due to excess of substrates. Leupeptin, on the other hand, caused a substantial inhibition of thiol proteinases; this block remained in the isolated AVs. Accordingly, leupeptin-induced AVs displayed decreased protein degradation following shorter exposure times. Later, when leupeptin was metabolized, catch-up proteolysis was noted. The differing mechanisms of action of the inhibitors were also apparent as regards lipid contents and lipolysis. Whereas chloroquine and vinblastine increased the amounts of cholesterol and triglycerides parallel to proteins, leupeptin had no such effect. Lipolysis proceeded at normal rate following leupeptin administration, which was not the case after vinblastine and chloroquine exposure. Leupeptin has no effect on acid lipases; therefore lipids do not accumulate in AVs of hepatocytes that are exposed to leupeptin.
Exp Mol Pathol 1987 Dec
PMID:Comparison of different autophagic vacuoles with regard to ultrastructure, enzymatic composition, and degradation capacity--formation of crinosomes. 367 66

Highly sensitive and specific synthetic substrates were used to quantitate cathepsin B and D activity in peritoneal macrophages in response to stimulation in vivo with mineral oil and thioglycollate. After intraperitoneal instillation of mineral oil the activity of cathepsin B increased significantly (to 15 300 units/mg protein versus 7 340 in saline controls), reaching values approaching those found in alveolar macrophages (18 400 units/mg protein). Significantly greater stimulation of enzyme activity was obtained after intraperitoneal instillation of thioglycollate (23 600 units/mg protein). Cathepsin D activity also increased significantly after both mineral oil and thioglycollate. However, the increase was moderate (from 806 to about 1 200 units/mg protein), remaining still more than six times lower than in alveolar macrophages. The data are the first to demonstrate that cathepsin B activity can be stimulated in vivo in peritoneal macrophages by instillation of agents that induce acute inflammation. They also point to a differential control of expression of cathepsin B and D activity in both peritoneal and alveolar macrophages in spite of the common lysosomal origin of the two enzymes.
Mol Cell Biochem 1985 Nov
PMID:Cathepsin B and D activity in stimulated peritoneal macrophages. 407 20

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.
J Mol Cell Cardiol 1983 Aug
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 hookworm Ancylostoma caninum induces human eosinophilic enteritis (EE), probably via allergic responses to its secretions. Cysteine and metallo-proteinases may be the components of these secretions that elicit hypersensitivity reactions. In order to characterize genes encoding cysteine proteinases (CP) secreted by A. caninum, an adult hookworm cDNA library was constructed and screened with a cloned fragment of a hookworm CP gene. This fragment was obtained using consensus oligonucleotide, CP-gene-specific primers in the polymerase chain reaction. cDNAs encoding two CPs were obtained from the library and sequenced. The first gene, AcCP-1, encoded a cathepsin B-like zymogen CP of 343 amino acids (aa), predicted to be processed in vivo into a mature CP of 255 aa. Closest nucleotide identities were to Haemonchus contortus cysteine protease (61%) and to human cathepsin B (60%). The second gene, AcCP-2, encoded a mature CP of 254 aa, that showed 86% identity to AcCP-1, and 58% and 47% identity to bovine cathepsin B and human cathepsin B, respectively. Rabbit antisera raised against recombinant AcCP-1 reacted with esophageal, amphidial and excretory glands in formalin-fixed, paraffin embedded sections of both male and female adult hookworms, and with an antigen of approx. 40 kDa in Western blot analysis of excretory/secretory products from adult hookworms. Together, these immuno-hybridization results strongly suggest that the CP encoded by the AcCP-1 gene is secreted by hookworms. These are the first reported CP genes from hookworms. Proteinases encoded by these genes may be responsible for the CP activity that we have shown previously to be secreted by adult A. caninum.
Mol Biochem Parasitol 1995 May
PMID:Characterization and localization of cathepsin B proteinases expressed by adult Ancylostoma caninum hookworms. 747 98

Sequence analysis of a 1.33 kb clone from a root cDNA library of Nicotiana rustica revealed an open reading frame encoding a protein of 356 amino acids. The deduced protein has high levels of homology to human cathepsin B protease and a cathepsin B-like cysteine protease from wheat but much lower levels of homology with other plant cysteine proteinases. Southern blotting experiments suggest a limited number of cathepsin B-like genes are present in the genome of N. rustica and also that of N. tabacum. RNA analysis involving a range of tissues, harvested from both Nicotiana species 4-5 h after the beginning of a 16 h photoperiod, revealed the cathepsin B-like gene was being expressed strongly in roots, stem and developing flowers but weakly in mature leaves. Further analysis of RNA extracted from leaf tissue of N. tabacum revealed the gene showed rhythmic expression and also that its expression increased in response to wounding. Analysis of leaf tissues harvested during the latter part of a 16 h photoperiod (11 and 16 h after illumination commenced) showed that transcript levels were two three times higher than in leaf tissue harvested either towards the end of the dark period or 5 h after illumination commenced. When leaf tissue was wounded at 11:00 (5 h after plants were illuminated), and harvested for RNA extraction 6 h later, the level of cathepsin B-like transcript in mesophyll tissue was found to be increased ca. 2-fold relative to the level detected in unwounded controls.
Plant Mol Biol 1995 Oct
PMID:Isolation and expression pattern of a cDNA encoding a cathepsin B-like protease from Nicotiana rustica. 757 87

The elucidation of the enzymatic processing mechanism associated with the formation of antigenic peptide fragments that combine with MHC class II molecules is fundamental to our understanding of the immune system. We have investigated a structurally well defined protein, recombinant human growth hormone (rhGH), as an antigen, and present data supporting the hypothesis that the enzyme cathepsin B can produce peptide fragments bearing T cell epitopes associated with lymphocyte proliferative response to hGH in Balb/c (H-2dhaplotype) mice. Minimal T cell epitopes are not generated; rather the cathepsin cleavage sites flank the three antigenic peptide regions, amino acid residues 31-41, 81-100, and 166-181.
Mol Immunol 1993 Apr
PMID:Evidence supporting a role for cathepsin B in the generation of T cell antigenic epitopes of human growth hormone. 768 51

Phylogenetic analyses of the major family of cysteine proteinases of eukaryotes revealed that this family has been characterized by numerous gene duplications, several of which occurred very early in eukaryote evolutionary history. For example, certain cysteine proteinases from plants and animals are homologous to each of the two cysteine proteinases of the protist Dictyostelium discoideum, indicating that these genes duplicated prior to the divergence of Dictyostelium, plants, and animals. All members of this gene family from metazoan parasites clustered in a well-defined subfamily with mammalian cathepsin B, whereas all those from protist parasites clustered outside this subfamily. Five members of this subfamily from Haemonchus contortus (a nematode parasite of sheep and other ruminants) evolved by gene duplications which were estimated to have occurred within the past 200 My. The proteins encoded by these five genes show a surprising number of residue charge differences from each other, particularly in helical regions in or near the substrate-binding cleft. Statistical analysis of DNA sequences showed that nonsynonymous nucleotide differences that cause amino acid residue charge changes have occurred in these regions at a greater rate than expected under random substitution, suggesting that these genes have diversified as a result of positive natural selection favoring such changes.
Mol Phylogenet Evol 1994 Dec
PMID:Evolution of cysteine proteinases in eukaryotes. 769 89

We examined the effects of a synthetic glucocorticoid (dexamethasone; Dex) on protoeolysis and on protease messenger RNA (mRNA) concentrations in rat L8 skeletal myotube cultures. Protein degradation was measured as release of radioactive trichloroacetic acid-soluble material from intracellular proteins pre-labelled with [3H]tyrosine. Dex (1 microM) stimulated protein degradation (P < 0.01). This effect was entirely blocked by the glucocorticoid antagonist, RU38486 (mifepristone; P < 0.01). Hence, actions of Dex on muscle protein degradation are mediated via intracellular glucocorticoid receptors. Molecular mechanisms by which glucocorticoids stimulate protein degradation in skeletal muscle are not known. Here, we investigated the regulation of protease (cathepsin B, cathepsin D, proteasome C2 subunit and m-calpain) mRNA concentrations by Dex in cultured L8 muscle cells. Cathepsin B mRNA concentration was enhanced 3.3-fold by Dex. This effect was blocked by RU38486. RU38486 alone did not affect cathepsin B mRNA concentration or mRNAs of other proteases. Concentrations of cathepsin D and m-calpain mRNAs were also increased by Dex. These effects were also abolished by RU38486. Proteasome C2 mRNA was unaffected by Dex and Dex reduced alpha-tubulin mRNA. Thus, glucocorticoids specifically regulate the concentrations of mRNAs encoding some proteases in muscle cells. The regulation of protease mRNA concentration is mediated via interaction between Dex with glucocorticoid receptors and is independent of the actions of Dex on mRNA encoding house-keeping proteins. These changes may underlie glucocorticoid-dependent control of proteolysis in muscle.
Mol Cell Endocrinol 1995 Feb 27
PMID:Effects of dexamethasone on protein degradation and protease gene expression in rat L8 myotube cultures. 775 36

The important components of mucopolysaccharides and collagen have been analyzed in tissues of control and carcinoma of uterine cervix. Among these components hyaluronic acid and chondroitin sulphate levels were found to be increased, whereas decreased level of collagen was observed in uterine cervical carcinoma. Serum cathepsin B, D and acid and alkaline phosphatases have also been analyzed in controls and carcinoma patients before and after treatments. The activities of these enzymes have been found to increase prominently in advanced stages. Among these enzymes cathepsin B and alkaline phosphatase have exhibited remarkable increase in activity in uterine cervical carcinoma. Different modes of treatment exerted reversion of the elevated activities of these enzymes. However, combined therapy type II (radiation combined with cisplatin and cyclophosphomide) seems to be more effective in reverting the activities of these enzymes to normal levels.
Mol Cell Biochem 1995 Mar 09
PMID:Extracellular matrix components and proteolytic enzymes in uterine cervical carcinoma. 779 43

This report presents the deduced amino acid sequence of a novel cathepsin L proteinase from Schistosoma mansoni, and describes cathepsin L-like activity in extracts of adult schistosomes. Using consensus primers specific for cysteine proteinases, gene fragments were amplified from adult S. mansoni cDNA by PCR and cloned. One of these fragments showed marked identity to Sm31, the cathepsin B cysteine proteinase of adult S. mansoni, whereas another differed from Sm31 and was employed as a probe to isolate two cDNAs from an adult S. mansoni gene library. Together these cDNAs encoded a novel preprocathepsin L of 319 amino acids; this zymogen is predicted to be processed in vivo into a mature, active cathepsin L proteinase of 215 amino acids. Closest homologies were with cathepsins L from rat, mouse, and chicken (46-47% identity). Southern hybridization analysis suggested that only one or a few copies of the gene was present per genome, demonstrated that its locus was distinct from that of Sm31, and that a homologous sequence was present in Schistosoma japonicum. Because these results indicated that schistosomes expressed a cathepsin L proteinase, extracts of adult S. mansoni were examined for acidic, cysteine proteinase activity. Based on rates of cleavage of peptidyl substrates employed to discriminate between classes of cysteine proteinases, namely cathepsin L (Z-phe-arg-AMC), cathepsin B (Z-arg-arg-AMC) and cathepsin H (Bz-arg-AMC), the extracts were found to contain vigorous cathepsin L-like activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biochem Parasitol 1994 Sep
PMID:Adult Schistosoma mansoni express cathepsin L proteinase activity. 783 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>