Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Cathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Cathepsin L: A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.Cathepsin D: An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC (Formerly EC K: A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.Cathepsin G: A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.Cathepsin H: An ubiquitously-expressed lysosomal cysteine protease that is involved in protein processing. The enzyme has both endopeptidase and aminopeptidase activities.Cathepsin E: An aspartic endopeptidase that is similar in structure to CATHEPSIN D. It is found primarily in the cells of the immune system where it may play a role in processing of CELL SURFACE ANTIGENS.Cathepsin C: A papain-like cysteine protease that has specificity for amino terminal dipeptides. The enzyme plays a role in the activation of several pro-inflammatory serine proteases by removal of their aminoterminal inhibitory dipeptides. Genetic mutations that cause loss of cathepsin C activity in humans are associated with PAPILLON-LEFEVRE DISEASE.Cathepsin F: A lysosomal papain-related cysteine proteinase that is expressed in a broad variety of cell types.Cathepsin Z: A ubiquitously-expressed cysteine peptidase that exhibits carboxypeptidase activity. It is highly expressed in a variety of immune cell types and may play a role in inflammatory processes and immune responses.Cysteine Endopeptidases: ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.Cathepsin W: A cysteine endopeptidase found in NATURAL KILLER CELLS and CYTOTOXIC T-LYMPHOCYTES. It may have a specific function in the mechanism or regulation of cytolytic activity of immune cells.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Cathepsin A: A carboxypeptidase that catalyzes the release of a C-terminal amino acid with a broad specificity. It also plays a role in the LYSOSOMES by protecting BETA-GALACTOSIDASE and NEURAMINIDASE from degradation. It was formerly classified as EC and EC N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.Cystatins: A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Cysteine Proteinase Inhibitors: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.DiazomethaneDipeptides: Peptides composed of two amino acid units.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC B: An intracellular cystatin subtype that is found in a broad variety of cell types. It is a cytosolic enzyme inhibitor that protects the cell against the proteolytic action of lysosomal enzymes such as CATHEPSINS.Cysteine Proteases: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.Enzyme Precursors: Physiologically inactive substances that can be converted to active enzymes.Cystatin A: A cytastin subtype found at high levels in the SKIN and in BLOOD CELLS. Cystatin A incorporates into the cornified cell envelope of stratified squamous epithelial cells and may play a role in bacteriostatic properties of skin.Pancreatic Elastase: A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Papillon-Lefevre Disease: Rare, autosomal recessive disorder occurring between the first and fifth years of life. It is characterized by palmoplantar keratoderma with periodontitis followed by the premature shedding of both deciduous and permanent teeth. Mutations in the gene for CATHEPSIN C have been associated with this disease.Cystatin C: An extracellular cystatin subtype that is abundantly expressed in bodily fluids. It may play a role in the inhibition of interstitial CYSTEINE PROTEASES.Fasciola hepatica: A species of helminth commonly called the sheep liver fluke. It occurs in the biliary passages, liver, and gallbladder during various stages of development. Snails and aquatic vegetation are the intermediate hosts. Occasionally seen in man, it is most common in sheep and cattle.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Benzoylarginine-2-Naphthylamide: An enzyme substrate which permits the measurement of peptide hydrolase activity, e.g. trypsin and thrombin. The enzymes liberate 2-naphthylamine, which is measured by colorimetric procedures.Kinetics: The rate dynamics in chemical or physical systems.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Dipeptidyl-Peptidases and Tripeptidyl-Peptidases: A subclass of exopeptidases that includes enzymes which cleave either two or three AMINO ACIDS from the end of a peptide chain.Leucine: An essential branched-chain amino acid important for hemoglobin formation.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Mannosephosphates: Phosphoric acid esters of mannose.Oligopeptides: Peptides composed of between two and twelve amino acids.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)T-Lymphocytes, Cytotoxic: Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.ElastinNK Cell Lectin-Like Receptor Subfamily K: An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.

Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. (1/1976)

The lysosomal cysteine proteases cathepsins S and L play crucial roles in the degradation of the invariant chain during maturation of MHC class II molecules and antigen processing. The p41 form of the invariant chain includes a fragment which specifically inhibits cathepsin L but not S. The crystal structure of the p41 fragment, a homologue of the thyroglobulin type-1 domains, has been determined at 2.0 A resolution in complex with cathepsin L. The structure of the p41 fragment demonstrates a novel fold, consisting of two subdomains, each stabilized by disulfide bridges. The first subdomain is an alpha-helix-beta-strand arrangement, whereas the second subdomain has a predominantly beta-strand arrangement. The wedge shape and three-loop arrangement of the p41 fragment bound to the active site cleft of cathepsin L are reminiscent of the inhibitory edge of cystatins, thus demonstrating the first example of convergent evolution observed in cysteine protease inhibitors. However, the different fold of the p41 fragment results in additional contacts with the top of the R-domain of the enzymes, which defines the specificity-determining S2 and S1' substrate-binding sites. This enables inhibitors based on the thyroglobulin type-1 domain fold, in contrast to the rather non-selective cystatins, to exhibit specificity for their target enzymes.  (+info)

Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro. (2/1976)

The acute hepatotoxicity induced by alpha-naphthylisothiocyanate (ANIT) in rats is manifested as neutrophil-dependent necrosis of bile duct epithelial cells (BDECs) and hepatic parenchymal cells. This hepatotoxicity mirrors that of drug-induced cholangiolitic hepatitis in humans. Since BDECs are primary targets of ANIT-induced toxicity, we hypothesized that after exposure to ANIT, BDECs produce a factor(s) that causes neutrophil chemotaxis and neutrophil-dependent hepatocellular injury. To test this hypothesis BDECs were isolated from male Sprague Dawley rats and incubated with ANIT (6.25, 12.5, 25, or 50 microM) or vehicle for 24 h. The conditioned medium (CM) was collected and placed in the bottom chamber of a two-chambered chemotaxis system, while isolated neutrophils were placed in the top chamber. Chemotaxis was indicated by neutrophil migration through a membrane to the bottom chamber. CM from BDECs exposed to each concentration of ANIT was chemotactic, whereas CM from vehicle-treated BDECs was not. ANIT alone caused a modest degree of chemotaxis at 50 microM. The conditioned media were added to isolated hepatocytes or to hepatocyte-neutrophil cocultures and incubated for 24 h. Hepatocyte toxicity was indicated by alanine aminotransferase release into the culture medium. CM from vehicle-treated BDECs did not cause hepatocyte killing in either hepatocyte-neutrophil cocultures or hepatocyte cultures. In contrast, the addition of CM from ANIT-treated BDECs (CM-BDEC-A) to hepatocyte-neutrophil cocultures resulted in hepatocyte killing. The same CM was not cytotoxic to hepatocyte cultures devoid of neutrophils. The hepatocyte killing could not be explained by residual ANIT in the CM, which was below the limit of detection (< or = 0.5 microM). The addition of antiproteases afforded protection against neutrophil-dependent hepatocellular injury induced by CM-BDEC-A. These results indicate that ANIT causes BDECs to release a factor(s) that attracts neutrophils and stimulates them to injure hepatocytes in vitro.  (+info)

Crystal structure of wild-type human procathepsin K. (3/1976)

Cathepsin K is a lysosomal cysteine protease belonging to the papain superfamily. It has been implicated as a major mediator of osteoclastic bone resorption. Wild-type human procathepsin K has been crystallized in a glycosylated and a deglycosylated form. The latter crystals diffract better, to 3.2 A resolution, and contain four molecules in the asymmetric unit. The structure was solved by molecular replacement and refined to an R-factor of 0.194. The N-terminal fragment of the proregion forms a globular domain while the C-terminal segment is extended and shows substantial flexibility. The proregion interacts with the enzyme along the substrate binding groove and along the proregion binding loop (residues Ser138-Asn156). It binds to the active site in the opposite direction to that of natural substrates. The overall binding mode of the proregion to cathepsin K is similar to that observed in cathepsin L, caricain, and cathepsin B, but there are local differences that likely contribute to the specificity of these proregions for their cognate enzymes. The main observed difference is in the position of the short helix alpha3p (67p-75p), which occupies the S' subsites. As in the other proenzymes, the proregion utilizes the S2 subsite for anchoring by placing a leucine side chain there, according to the specificity of cathepsin K toward its substrate.  (+info)

The intracellular serpin proteinase inhibitor 6 is expressed in monocytes and granulocytes and is a potent inhibitor of the azurophilic granule protease, cathepsin G. (4/1976)

The monocyte and granulocyte azurophilic granule proteinases elastase, proteinase 3, and cathepsin G are implicated in acute and chronic diseases thought to result from an imbalance between the secreted proteinase(s) and circulating serpins such as alpha1-proteinase inhibitor and alpha1-antichymotrypsin. We show here that the intracellular serpin, proteinase inhibitor 6 (PI-6), is present in monocytes, granulocytes, and myelomonocytic cell lines. In extracts from these cells, PI-6 bound an endogenous membrane-associated serine proteinase to form an sodium dodecyl sulfate (SDS)-stable complex. Using antibodies to urokinase, elastase, proteinase 3, or cathepsin G, we demonstrated that the complex contains cathepsin G. Native cathepsin G and recombinant PI-6 formed an SDS-stable complex in vitro similar in size to that observed in the extracts. Further kinetic analysis demonstrated that cathepsin G and PI-6 rapidly form a tight 1:1 complex (ka = 6.8 +/- 0.2 x 10(6) mol/L-1s-1 at 17 degrees C; Ki = 9.2 +/- 0.04 x 10(-10) mol/L). We propose that PI-6 complements alpha1-proteinase inhibitor and alpha1-antichymotrypsin (which control extracellular proteolysis) by neutralizing cathepsin G that leaks into the cytoplasm of monocytes or granulocytes during biosynthesis or phagocytosis. Control of intracellular cathepsin G may be particularly important, because it has recently been shown to activate the proapoptotic proteinase, caspase-7.  (+info)

Cathepsin S required for normal MHC class II peptide loading and germinal center development. (5/1976)

Major histocompatibility complex (MHC) class II molecules acquire antigenic peptides after degradation of the invariant chain (Ii), an MHC class II-associated protein that otherwise blocks peptide binding. Antigen-presenting cells of mice that lack the protease cathepsin S fail to process Ii beyond a 10 kDa fragment, resulting in delayed peptide loading and accumulation of cell surface MHC class II/10 kDa Ii complexes. Although cathepsin S-deficient mice have normal numbers of B and T cells and normal IgE responses, they show markedly impaired antibody class switching to IgG2a and IgG3. These results indicate cathepsin S is a major Ii-processing enzyme in splenocytes and dendritic cells. Its role in humoral immunity critically depends on how antigens access the immune system.  (+info)

Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. (6/1976)

Cathepsins have been implicated in the degradation of proteins destined for the MHC class II processing pathway and in the proteolytic removal of invariant chain (Ii), a critical regulator of MHC class II function. Mice lacking the lysosomal cysteine proteinase cathepsin S (catS) demonstrated a profound inhibition of Ii degradation in professional APC in vivo. A marked variation in the generation of MHC class II-bound Ii fragments and presentation of exogenous proteins was observed between B cells, dendritic cells, and macrophages lacking catS. CatS-deficient mice showed diminished susceptibility to collagen-induced arthritis, suggesting a potential therapeutic target for regulation of immune responsiveness.  (+info)

Characterization of novel cathepsin K mutations in the pro and mature polypeptide regions causing pycnodysostosis. (7/1976)

Cathepsin K, a lysosomal cysteine protease critical for bone remodeling by osteoclasts, was recently identified as the deficient enzyme causing pycnodysostosis, an autosomal recessive osteosclerotic skeletal dysplasia. To investigate the nature of molecular lesions causing this disease, mutations in the cathepsin K gene from eight families were determined, identifying seven novel mutations (K52X, G79E, Q190X, Y212C, A277E, A277V, and R312G). Expression of the first pro region missense mutation in a cysteine protease, G79E, in Pichia pastoris resulted in an unstable precursor protein, consistent with misfolding of the proenzyme. Expression of five mature region missense defects revealed that G146R, A277E, A277V, and R312G precursors were unstable, and no mature proteins or protease activity were detected. The Y212C precursor was activated to its mature form in a manner similar to that of the wild-type cathepsin K. The mature Y212C enzyme retained its dipeptide substrate specificity and gelatinolytic activity, but it had markedly decreased activity toward type I collagen and a cathepsin K-specific tripeptide substrate, indicating that it was unable to bind collagen triple helix. These studies demonstrated the molecular heterogeneity of mutations causing pycnodysostosis, indicated that pro region conformation directs proper folding of the proenzyme, and suggested that the cathepsin K active site contains a critical collagen-binding domain.  (+info)

Vaccination with cathepsin L proteinases and with leucine aminopeptidase induces high levels of protection against fascioliasis in sheep. (8/1976)

The potential of different parasite proteinases for use as vaccine candidates against fascioliasis in sheep was studied by vaccinating animals with the cathepsin L proteinases CL1 and CL2 and with leucine aminopeptidase (LAP) purified from adult flukes. In the first trial, sheep were immunized with CL1 or CL2 and the mean protection levels obtained were 33 and 34%, respectively. Furthermore, a significant reduction in egg output was observed in sheep vaccinated either with CL1 (71%) or with CL2 (81%). The second trial was performed to determine the protective potential of the two cathepsin L proteinases assayed together, as well as in combination with LAP, and of LAP alone. The combination of CL1 and CL2 induced higher levels of protection (60%) than those produced when these enzymes were administered separately. Those sheep that received the cocktail vaccine including CL1, CL2, and LAP were significantly protected (78%) against metacercarial challenge, but vaccination with LAP alone elicited the highest level of protection (89%). All vaccine preparations induced high immunoglobulin G titers which were boosted after the challenge infection, but no correlations between antibody titers and worm burdens were found. However, the sera of those animals vaccinated with LAP contained LAP-neutralizing antibodies. Reduced liver damage, as assessed by the level of the liver enzyme gamma-glutamyl transferase, was observed in the groups vaccinated with CL1, CL2, and LAP or with LAP alone.  (+info)

  • Cysteine cathepsin proteases contribute to many normal cellular functions, and their aberrant activity within various cell types can contribute to many diseases, including breast cancer. (
  • It is now well accepted that cathepsin proteases have numerous cell-specific functions within the tumor microenvironment that function to promote tumor growth and invasion, such that they may be valid targets for anti-metastatic therapeutic approaches. (
  • One intriguing therapeutic target of Au( I) is the cathepsin family of lysosomal cysteine proteases. (
  • In mice bearing highly metastatic tumors, we detected abundant cysteine cathepsin expression and activity in myeloid-derived suppressor cells (MDSCs). (
  • This highlights a potential role for cysteine cathepsin activity in suppressing the fusion of osteoclast precursor cells. (
  • In breast cancer over-expression of Cathepsin L is defined of one of the strongest prognostic factors for a subgroup of patients with node negative breast tumors. (
  • The availability of a purified preparation of salmon muscle cathepsins should stimulate interest and research in the characterization of these enzymes and lead to better means for the control of catheptic activity in fish muscle. (
  • In order to analyze further this function we investigated the activity of cathepsin S in comparison with cathepsins B and L. These enzymes were suggested to be involved in antigen presentation. (
  • In support of this hypothesis, we found that expression and activity of key cysteine cathepsins were downregulated during MDSC-osteoclast differentiation. (
  • In contrast to this, in syngeneic Epstein-Barr virus-transformed B cells the level of cathepsin B activity was found to be 10% of that in the corresponding keratinocytes, whereas the activities for cathepsins L and S were in a similar range. (
  • Specific catalytic activities of these cathepsins were determined fluorometrically by hydrolysis of a synthetic substrate (Z-Phe-Arg-7-amido-4-methylcoumarin) in subcellular fractions of human keratinocytes. (
  • It was found that the human keratinocyte cell line HaCaT exhibits activities of all three cathepsins investigated. (
  • Normal human keratinocytes in primary culture show a comparable pattern of cathepsin activities. (
  • This report documents that cathepsin S in human keratinocytes is selectively upregulated, in parallel to major histocompatibility complex class II molecules, in response to a pro-inflammatory cytokine. (
  • Publications] K.Ishidoh: 'Gene structure and 5^'ーupstream sequence of rat cathepsin L' FEBS Lett.259. (
  • Publications] K.Ishidoh: 'Gene structure of rat cathepsin H' FEBS Lett.253. (
  • Cysteine cathepsins belong to the papain-like family C1 of clan CA cysteine peptidases. (
  • Moreover, cysteine cathepsins are active in pericellular environments as soluble enzymes or bound to cell surface receptors at the plasma membrane, and possibly even within secretory vesicles, the cytosol, mitochondria, and within the nuclei of eukaryotic cells. (
  • Proteolytic actions performed by cysteine cathepsins are essential in the maintenance of homeostasis and depend heavily upon their correct sorting and trafficking within cells. (
  • This review focuses upon the transport pathways directing cysteine cathepsins to their points of action and thus emphasizes the broader role and functionality of cysteine cathepsins in a number of specific cellular locales. (
  • Arampatzidou M, Rehders M, Dauth S, Yu DMT, Tedelind S, Brix K. Imaging of protease functions-current guide to spotting cysteine cathepsins in classical and novel scenes of action in mammalian epithelial cells and tissues. (
  • We conclude that in lung cancers the three lysosomal enzymes are regulated in a noncoordinate manner and that there is specific induction of cysteine cathepsins. (
  • A composite docking approach for the identification and characterization of ectosteric inhibitors of cathepsin K. Law S, et al . (
  • The availability of a purified preparation of salmon muscle cathepsins should stimulate interest and research in the characterization of these enzymes and lead to better means for the control of catheptic activity in fish muscle. (
  • It is widely held that invasion is facilitated by a membrane or secreted form of cathepsin B that acts outside the cell to degrade ECM components at or adjacent to the surface of the invading cell. (
  • These cells were tested in an in vitro Matrigel invasion assay with membrane-permeant and impermeant inhibitors of cathepsin B. The results, which provided direct proof for the participation of cathepsin B in matrix penetration, also yielded the unexpected finding that an intracellular form of cathepsin B was required for Matrigel invasion. (
  • Sputum cathepsin B had greater stability at pH 7.5 and a higher apparent Mr, even after deglycosylation, than lysosomal cathepsin B. We conclude that the form of cathepsin B found in sputum is probably a truncated form of human procathepsin B, with some differences in properties that could be of physiological importance. (
  • Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans. (
  • These data suggest that cad-1 is a structural gene for cathepsin D. (
  • These results suggest that the ecdysone response elements are vital for activation of the promoter by 20-hydroxyecdysone (20E) in the larval fat body and further support the crucial role of ecdysone signaling to control cathepsin D gene transcription. (
  • By making use of EST data, sequenced cDNAs, and genomic trace sequences of the pea aphid Acyrthosiphon pisum, we identified a total of 28 cathepsin B-like gene copies in the genome of A. pisum. (
  • In addition, this work also implicates Cathepsin B genes in senescence, a developmental form of PCD, via regulation of the senescence marker gene Senescence Associated Gene 12 ( SAG12 ). (
  • Here, we report that in peripheral nerve-injured rats, the lysosomal cysteine protease cathepsin S (CatS) is critical for the maintenance of neuropathic pain and spinal microglia activation. (
  • We have recently found that after peripheral nerve injury, the mRNA for the lysosomal cysteine protease cathepsin S (CatS) was up-regulated in the DRG because of CatS expression in infiltrating macrophages ( 5 ). (
  • The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain: an immunocytochemical study," American Journal of Pathology , vol. 146, no. 4, pp. 848-860, 1995. (
  • Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. (
  • Recent work shows that the cysteine protease cathepsin S (Cat S) is required for the terminal step in CLIP formation in B cells and most dendritic cells (DCs), and in vitro can mediate all steps of digestion of class II-Ii complexes ( 20 , 21 , 22 , 23 , 24 , 25 ). (
  • The protease cathepsin D is one such target involved in several diseases such as tumors, degenerative processes, and vital processes of parasites causing schistosomiasis. (
  • Here, we have found that one important mechanism by which peptide modulation of the receptor enhances axon outgrowth is through secretion of a protease, Cathepsin B, which enables digestion of CSPGs. (
  • Cathepsin zymography separates different cathepsins based on their migration through a polyacrylamide gel co-polymerized with a gelatin substrate. (
  • The gel is then put into an activation buffer of a specific pH and left to incubate overnight at 37 °C. This activation step allows the cathepsins to degrade the gelatin substrate. (
  • BioVision's newly developed Cathepsin Activity Assay kits are fluorescence-based assays that utilize the preferred substrate sequence for each cathepsin, labeled with AFC (amino-4-trifluoromethyl coumarin). (
  • Cell lysates or other samples that contain cathepsins will cleave the synthetic substrate to release free AFC. (
  • Cathepsin F has the substrate specificity similar to that of cathepsins L and S. (
  • Leukocyte cathepsin S is a potent regulator of both cell and matrix turnover in advanced atherosclerosis," Arteriosclerosis, Thrombosis, and Vascular Biology , vol. 29, no. 2, pp. 188-194, 2009. (
  • We further demonstrate that incorporating a cathepsin B-cleavable linker between the BIM BH3 peptide and the hydrophobic tail within individual amphiphiles results in increased binding to recombinant BCL-2 proteins while also allowing for increased cellular uptake and mitochondrial localization leading to faster and more potent dose-dependent cytotoxicity and caspase activation in malignant cells. (
  • Novel, Nonpeptidic Cyanamides as Potent and Reversible Inhibitors of Human Cathepsins K and L, J. Med. (
  • The area of contact is slightly larger than in chagasin complexes with the endopeptidase, cathepsin L. However, residues important for high affinity to both enzymes are mainly found in the outer loops L4 and L6 of chagasin. (
  • Cathepsin B possesses both endopeptidase and exopeptidase activities, in the latter case acting as a peptidyl-dipeptidase. (
  • In particular, no defects in granulopoiesis or PMN homeostasis have been reported in mice deficient in cathepsin G ( CG −/− ), 15 neutrophil elastase ( NE −/− ), 16 , 17 or dipeptidylpeptidase I ( DPPI −/− ), which lack active NSPs. (
  • Neutrophil cathepsin G increases calcium flux and inositol polyphosphate production in cultured endothelial cells. (
  • Exposure of endothelial cells (ENDO) to human neutrophil cathepsin G (CG) increases albumin flux across the endothelial monolayer. (
  • Identification of a human neutrophil angiotension II-generating protease as cathepsin G. J Clin Invest. (
  • Cathepsin L-deficient mice were shown to have less adipose tissue, lower serum glucose and insulin levels, more insulin receptor subunits, more glucose transporter (GLUT4) and more fibronectin than wild type controls. (
  • To test this, we used an immunocompetent endometriosis mouse model and found that endometriotic lesions exhibited a greater than 5-fold increase in active cathepsins compared to tissue from peritoneal wall or eutopic endometrium, with cathepsins L and K specifically implicated. (
  • Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. (
  • Platt's long-term research has focused on cathepsins, including the development of sensitive tools and assays to quantify their activity in cells and tissue, as well as potential diagnostic applications for breast, lung and cervical cancer. (
  • Keilová, H.: On the specificity and inhibition of cathepsins D and B. In: Tissue proteinases, ed. by A. J. Barrett and J. T. Dingle, p. 45-65. (
  • IHC image of Cathepsin D staining in Human Lung formalin fixed paraffin embedded tissue section, performed on a Leica Bond™ system using the standard protocol F. The section was pre-treated using heat mediated antigen retrieval with sodium citrate buffer (pH6, epitope retrieval solution 1) for 20 mins. (
  • Arkona C, Wiederanders B. Expression, subcellular distribution and plasma membrane binding of cathepsin B and gelatinases in bone metastatic tissue. (
  • Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women," Journal of Clinical Endocrinology and Metabolism , vol. 91, no. 3, pp. 1042-1047, 2006. (
  • The activity profiles of four cathepsins in the kidney and liver tissue were analysed and correlated with blood cytokines level in the presence and absence of antifungal compounds (amphotericin B, a standard drug and 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrole-2-yl)-1-methylethyl pentanoate, isolated in our laboratory from natural source) treatment. (
  • Cathepsins D, B, and L in malignant human lung tissue. (
  • The levels of cathepsins in malignant and surrounding nonmalignant lung tissue were determined in 17 non-small cell lung cancer specimens. (
  • Cathepsin F staining of paraffin-embedded human heart tissue sections. (
  • However, we here report an unexpected finding that cysteine protease genes of the family cathepsin B are massively amplified in the lineage of aphids, and that many of the protease genes exhibit gut-specific over-expression. (
  • Phylogenetic analyses of all the cathepsin B genes in aphids revealed that genic expansion has continuously proceeded with basal, intermediary and recent duplications. (
  • Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading," Immunity , vol. 4, no. 4, pp. 357-366, 1996. (
  • A direct immunohistochemical method of high specificity is presented for the demonstration of sites of cathepsin B1. (
  • In this review we cover specific roles of cathepsins in innate and adaptive immunity, as well as their implication in the pathogenesis of several diseases. (
  • It is of note to mention that this review is not meant to comprehensively cover the present literature on viruses encountering cathepsins but rather illustrates, on some representative examples, the possible roles of cathepsins in replication of viruses and in the course of disease. (
  • In meningioma, Cat L was a less-significant marker of invasion than Cat B. In contrast to cathepsins, the activities of endogenous cysteine peptidase inhibitors (CPIs), including stefins, cystatins and kininogens, were significantly higher in benign and atypical meningioma cell extracts than in malignant meningioma, and low-grade compared to high-grade astrocytoma. (
  • Data acquired from counting of cells staining positively of the cathepsins on the DAB IHC-stained slides and from Nanostring mRNA analysis were subjected to statistical analyses to determine significance. (
  • 2017. (