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.
A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.
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 3.4.23.5. (Formerly EC 3.4.4.23).
An ubiquitously-expressed lysosomal cysteine protease that is involved in protein processing. The enzyme has both endopeptidase and aminopeptidase activities.
A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.
A serine protease found in the azurophil granules of NEUTROPHILS. It has an enzyme specificity similar to that of chymotrypsin C.
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.
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.
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.
A lysosomal papain-related cysteine proteinase that is expressed in a broad variety of cell types.
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.
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)
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.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.
Peptides composed of two amino acid units.
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.
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.
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.
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 3.4.22.2.
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.
N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.
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 3.4.12.1 and EC 3.4.21.13.
Physiologically inactive substances that can be converted to active enzymes.
An extracellular cystatin subtype that is abundantly expressed in bodily fluids. It may play a role in the inhibition of interstitial CYSTEINE PROTEASES.
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)
A sub-class of PEPTIDE HYDROLASES that act only near the ends of polypeptide chains.
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.
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.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
The inactive proenzyme of trypsin secreted by the pancreas, activated in the duodenum via cleavage by enteropeptidase. (Stedman, 25th ed)
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 3.4.21.36.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The process of cleaving a chemical compound by the addition of a molecule of water.
The rate dynamics in chemical or physical systems.
An essential branched-chain amino acid important for hemoglobin formation.
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 3.4.21.37.
An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.
Peptides composed of between two and twelve amino acids.
A reagent used for the determination of iron.
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.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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)
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.
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.

Activation of Xenopus eggs by proteases: possible involvement of a sperm protease in fertilization. (1/980)

Egg activation in cross-fertilization between Xenopus eggs and Cynops sperm may be caused by a protease activity against Boc-Gly-Arg-Arg-MCA in the sperm acrosome. To determine the role of the sperm protease in fertilization, the protease was purified from Cynops sperm using several chromatographic techniques. We found that purified sperm protease readily hydrolyzes Boc-Gly-Arg-Arg-MCA and Z-Arg-Arg-MCA, that protease activity was inhibited by the trypsin inhibitors aprotinin and leupeptin, and that not only the purified protease, but also cathepsin B, induces activation in Xenopus eggs. We inseminated unfertilized Xenopus eggs with homologous sperm in the presence of various peptidyl MCA substrates or protease inhibitors and demonstrated that trypsin inhibitors or MCA substrates containing Arg-Arg-MCA reversibly inhibited fertilization of both fully jellied and denuded eggs. Sperm motility was not affected by the reagents. An extract obtained from Xenopus sperm showed hydrolytic activity against Boc-Gly-Arg-Arg-MCA, Z-Arg-Arg-MCA, and Arg-MCA. These results suggest that the tryptic protease in Xenopus sperm is involved in fertilization, most likely by participating in egg activation.  (+info)

Cathepsin B immunohistochemical staining in tumor and endothelial cells is a new prognostic factor for survival in patients with brain tumors. (2/980)

The cysteine endopeptidase, cathepsin (Cat) B, and its endogenous inhibitor, stefin A, were found relevant for cancer progression of many neoplasms, including human brain tumors. Histological sections of 100 primary brain tumors, 27 benign and 73 malignant, were stained immunohistochemically for Cat B and stefin A. The immunohistochemical staining of Cat B in tumor cells, endothelial cells, and macrophages was scored separately from 0-12. The score in tumor and endothelial cells was significantly higher in malignant tumors compared with benign tumors (P<0.000). A significant correlation between immunostaining of Cat B (scored together for tumor and endothelial cells) and clinical parameters, such as duration of symptoms, Karnofsky score, psycho-organic symptoms, and histological score was demonstrated. Univariate survival analysis indicated that total Cat B score above 8 was a significant predictor for shorter overall survival (P = 0.003). In glioblastoma multiforme, intense Cat B staining of endothelial cells was a significant predictor for shorter survival (P = 0.003). Stefin A immunostaining was weak and detected only in a few benign and some malignant tumors, suggesting that this inhibitor alone is not sufficient in balancing proteolytic activity of Cat B. We conclude that specific immunostaining of Cat B in tumor and endothelial cells can be used to predict the risk of death in patients with primary tumors of the central nervous system.  (+info)

Expression and alteration of the S2 subsite of the Leishmania major cathepsin B-like cysteine protease. (3/980)

The mature form of the cathepsin B-like protease of Leishmania major (LmajcatB) is a 243 amino acid protein belonging to the papain family of cysteine proteases and is 54% identical to human-liver cathepsin B. Despite the high identity and structural similarity with cathepsin B, LmajcatB does not readily hydrolyse benzyloxycarbonyl-Arg-Arg-7-amino-4-methyl coumarin (Z-Arg-Arg-AMC), which is cleaved by cathepsin B enzymes. It does, however, hydrolyse Z-Phe-Arg-AMC, a substrate typically cleaved by cathepsin L and B enzymes. Based upon computer generated protein models of LmajcatB and mammalian cathepsin B, it was predicted that this variation in substrate specificity was attributed to Gly234 at the S2 subsite of LmajcatB, which forms a larger, more hydrophobic pocket compared with mammalian cathepsin B. To test this hypothesis, recombinant LmajcatB was expressed in the Pichia pastoris yeast expression system. The quality of the recombinant enzyme was confirmed by kinetic characterization, N-terminal sequencing, and Western blot analysis. Alteration of Gly234 to Glu, which is found at the corresponding site in mammalian cathepsin B, increased recombinant LmajcatB (rLmajcatB) activity toward Z-Arg-Arg-AMC 8-fold over the wild-type recombinant enzyme (kcat/Km=3740+/-413 M-1.s-1 versus 472+/-72.4 M-1.s-1). The results of inhibition assays of rLmajcatB with an inhibitor of cathepsin L enzymes, K11002 (morpholine urea-Phe-homoPhe-vinylsulphonylphenyl, kinact/Ki=208200+/-36000 M-1. s-1), and a cathepsin B specific inhibitor, CA074 [N-(L-3-trans-propylcarbamoyloxirane-2-carbonyl)-l-isoleucyl-l- prolin e, kinact/Ki=199200+/-32900 M-1.s-1], support the findings that this protozoan protease has the P2 specificity of cathepsin L-like enzymes while retaining structural homology to mammalian cathepsin B.  (+info)

Kappa light chain-associated Fanconi's syndrome: molecular analysis of monoclonal immunoglobulin light chains from patients with and without intracellular crystals. (4/980)

Plasma cell dyscrasias may be responsible for Fanconi's syndrome, due to the toxicity of a free monoclonal kappa light chain toward kidney proximal tubules. Eight cases of Fanconi's syndrome were analyzed. We compared the structures of VkappaI variability subgroup V domains from five cases of Fanconi's syndrome and one myeloma without renal involvement. Among Fanconi cases, four putative structures were obtained after molecular modeling by homology, and the other had previously been refined by X-ray crystallography. The complete sequences of one VkappaI, one VkappaIII and N-terminal sequences of two VkappaI light chains, from patients with different forms of Fanconi's syndrome, were compared with four previously studied sequences. All three kappa chains responsible for a 'classical' form with intralysosomal crystals and a low mass myeloma, were encoded by the LCO2/O12 germline gene and had an unusual non-polar residue exposed to the solvent in the CDR-L1 loop. Of both VkappaI light chains from patients with Fanconi's syndrome without intracellular crystals, one derived from LCO2/O12 and the other from LCO8/O18 gene. Another feature that could be related to non-crystallization was the absence of accessible side chains in the CDR-L3 loop which is known to be implicated in dimer formation.  (+info)

Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis. (5/980)

OBJECTIVE: To examine the expression of the matrix metalloproteinase, MMP-1, and the cysteine proteases, cathepsin B (CB) and cathepsin L (CL), in the synovial membrane (SM) of patients with early inflammatory arthritis. METHODS: Samples of SM were obtained by blind needle biopsy or needle arthroscopy from inflamed knees of 28 patients with early inflammatory arthritis (mean disease duration 10.2 months, range 2 weeks-18 months). Sixteen patients had rheumatoid arthritis (RA), nine psoriatic arthritis and there was one each with ankylosing spondylitis, gout and an undifferentiated arthritis. Comparison was made with tissue from two patients with established erosive RA and three normal synovial tissue samples. In situ hybridization was performed using digoxigenin-labelled RNA probes. RESULTS: MMP-1, CB and CL were expressed in all patients with early arthritis and in established erosive RA, whereas normal synovium showed only scanty expression. The three proteases were prominent in perivascular infiltrates and endothelial cells of early arthritis tissue. MMP-1 was observed primarily in the lining layer, but was also evident in the sublining area. CB and CL were expressed to a lesser extent in the lining layer, and were present mainly in the subintima. The three proteases were not found in lymphoid aggregrates. No differences were observed between the disease categories. CONCLUSIONS: The detection of MMP-1, CB and CL in the synovium shortly after symptom onset implies that the potential for joint destruction exists at a very early stage in the disease. In addition, the perivascular and endothelial cell expression suggests a role for these proteases in mononuclear cell influx to the inflamed synovium and in angiogenesis.  (+info)

Antigen secreted from noncytosolic Listeria monocytogenes is processed by the classical MHC class I processing pathway. (6/980)

Intracellular bacteria can reside in a vacuolar compartment, or they can escape the vacuole and become free living in the cytoplasm. The presentation of Ag by class I MHC molecules has been defined primarily for Ag present in the cytoplasm. It was therefore thought that Ags from bacteria that remain in a vacuole would not be presented by MHC class I molecules. Although some studies have provided data to support this idea, it is not necessarily true for all intracellular bacteria. For example, we have previously demonstrated that an epitope from the p60 protein secreted by LLO- Listeria monocytogenes, which does not reside in the cytoplasm, can be presented by MHC class I molecules to a T cell clone specific for the epitope, p60217-225. We have further examined the route by which Ag secreted by LLO- L. monocytogenes is presented by MHC class I molecules. Using pharmacological inhibitors, we demonstrate that MHC class I presentation of the p60 epitope derived from by LLO- L. monocytogenes requires phagolysosome fusion and processing by the proteasome. Lysosomal cathepsins, however, are not required for processing of the p60 epitope. Similarly, processing of the AttM epitope, secreted by LLO- L. monocytogenes and presented by H2-M3, also requires phagolysosome fusion and cleavage by the proteasome. Thus, p60 and AttM secreted by LLO- L. monocytogenes are processed via the classical class I pathway for presentation by MHC class I molecules.  (+info)

The affinity and kinetics of inhibition of cysteine proteinases by intact recombinant bovine cystatin C. (7/980)

Recent studies have shown that the bovine cysteine proteinase inhibitor, cystatin C, is synthesized as a preprotein containing a 118-residue mature protein. However, the forms of the inhibitor isolated previously from bovine tissues had shorter N-terminal regions than expected from these results, and also lower affinity for proteinases than human cystatin C. In this work, we report the properties of recombinant, full-length bovine cystatin C having a complete N-terminal region. The general characteristics of this form of the inhibitor, as reflected by the isoelectric point, the far-ultraviolet circular dichroism spectrum, the thermal stability and the changes of tryptophan fluorescence on interaction with papain, resembled those of human cystatin C. The affinity and kinetics of inhibition of papain and cathepsins B, H and L by the bovine inhibitor were also comparable with those of the human inhibitor, although certain differences were apparent. Notably, the affinity of bovine cystatin C for cathepsin H was somewhat weaker than that of human cystatin C, and bovine cystatin C bound to cathepsin L with about a four-fold higher association rate constant than the human inhibitor. This rate constant is comparable with the highest values reported previously for cystatin-cysteine proteinase reactions. The full-length, recombinant bovine cystatin C bound appreciably more tightly to proteinases than the shorter form characterized previously. Digestion of the recombinant inhibitor with neutrophil elastase resulted in forms with truncated N-terminal regions and appreciably decreased affinity for papain, consistent with the forms of bovine cystatin C isolated previously having arisen by proteolytic cleavage of a mature, full-length inhibitor.  (+info)

Accumulation of sialic acid in endocytic compartments interferes with the formation of mature lysosomes. Impaired proteolytic processing of cathepsin B in fibroblasts of patients with lysosomal sialic acid storage disease. (8/980)

The impact of an altered endocytic environment on the biogenesis of lysosomes was studied in fibroblasts of patients suffering from sialic acid storage disease (SASD). This inherited disorder is characterized by the accumulation of acidic monosaccharides in lysosomal compartments and a concomitant decrease of their buoyant density. We demonstrate that C-terminal trimming of the lysosomal cysteine proteinase cathepsin B is inhibited in SASD fibroblasts. This late event in the biosynthesis of cathepsin B normally takes place in mature lysosomes, suggesting an impaired biogenesis of these organelles in SASD cells. When normal fibroblasts are loaded with sucrose, which inhibits transport from late endosomes to lysosomes, C-terminal cathepsin B processing is prevented to the same extent. Further characterization of the terminal endocytic compartments of SASD cells revealed properties usually associated with late endosomes/prelysosomes. In addition to a decreased buoyant density, SASD "lysosomes" show a reduced acidification capacity and appear smaller than their normal counterparts. We conclude that the accumulation of small non-diffusible compounds within endocytic compartments interferes with the formation of mature lysosomes and that the acidic environment of the latter organelles is a prerequisite for C-terminal processing of lysosomal hydrolases.  (+info)

Inflammatory breast cancer (IBC) is an aggressive, metastatic and highly angiogenic form of locally advanced breast cancer with a relatively poor three-year survival rate. Breast cancer invasion has been linked to proteolytic activity at the tumor cell surface. Here we explored a role for active cathepsin B on the cell surface in the invasiveness of IBC. We examined expression of the cysteine protease cathepsin B and the serine protease urokinase plasminogen activator (uPA), its receptor uPAR and caveolin-1 in two IBC cell lines: SUM149 and SUM190. We utilized a live cell proteolysis assay to localize in real time the degradation of type IV collagen by IBC cells. IBC patient biopsies were examined for expression of cathepsin B and caveolin-1. Both cell lines expressed comparable levels of cathepsin B and uPA. In contrast, levels of caveolin-1 and uPAR were greater in SUM149 cells. We observed that uPA, uPAR and enzymatically active cathepsin B were colocalized in caveolae fractions isolated from SUM149
Electrospray mass spectrometric techniques were used to demonstrate that mature (single-chain) recombinant rat cathepsin B is capable of sequentially removing the three dipeptides which comprise the C-terminal extension of the proenzyme. A pepsin-cleaved form of a non-active mutant recombinant rat procathepsin B (Cys-29-Ser) was used as a substrate to study C-terminal processing by mature cathepsin B. The results indicate that the first two residues (Arg-Phe) are removed efficiently, while the remaining four (Gln-Tyr-Trp-Gly), particularly the final two, are much more resistant to proteolysis. These cleavages were pronounced at pH 5.0 compared with pH 6.0, in agreement with the lower pH optimum for cathepsin B exopeptidase activity reported previously. From this example of the peptidyldipeptidase activity of cathepsin B we conclude that removal of the C-terminal extension may occur in any intracellular compartment where active cathepsin B is found. ...
|p||strong|CA-074|/strong|, a specific cathepsin B inhibitor, also abolished the neurotoxic effects caused by Abeta42-activated BV2 cell [1]. Co-treatment of cultures with the cathepsin B inhibitors CA-074 or Z-FA-FMK suppressed the cytostatic effects of
Mechanical stress plays a key role in the pathogenesis of cartilage destruction seen in osteoarthritis (OA). We investigated the effect of cyclic tensile stress (CTS) on the anabolic and catabolic gene expression of rat cultured normal chondrocytes using the Flexercell strain unit. The effects of interleukin (IL)-4, a chondroprotective cytokine, on the changes in gene expression induced by CTS were also investigated. CTS (7% elongation at 0.5 Hz) for 24 h did not affect the expression of aggrecan and type II collagen, whereas CTS significantly upregulated matrix metalloproteinase (MMP)-13 and cathepsin B mRNA expression by chondrocytes. IL-1beta expression was also signifi cantly upregulated by CTS up to 12 h. The upregulation of MMP-13 was observed at 3 h, which was earlier than that of IL-1beta. Furthermore, pre-treatment with IL-4 (10 ng/ml) suppressed both MMP-13 and cathepsin B induction by mechanical stress, as well as CTS-induced IL-1beta expression. Our results suggest that IL-4 might ...
1CPJ: CRYSTAL STRUCTURES OF RECOMBINANT RAT CATHEPSIN B AND A CATHEPSIN B-INHIBITOR COMPLEX: IMPLICATIONS FOR STRUCTURE-BASED INHIBITOR DESIGN
CA-074 methyl ester is a cell-permeable analog of CA-074 that acts as an irreversible cathepsin B inhibitor. CA-074 methyl ester is reported to inhibit bone resorption in rodent models and shown to inhibit B16 melanoma cell invasion in vitro.
Vectors based on different serotypes of adeno-associated virus hold great promise for human gene therapy, based on their unique tissue tropisms and distinct immunological profiles. A particularly interesting candidate is AAV8, which can efficiently and rapidly transduce a wide range of tissues in vivo. To further unravel the mechanisms behind AAV8 transduction, we used yeast two-hybrid analyses to screen a mouse liver complementary DNA library for cellular proteins capable of interacting with the viral capsid proteins. In total, we recovered approximately 700 clones, comprising over 300 independent genes. Sequence analyses revealed multiple hits for over 100 genes, including two encoding the endosomal cysteine proteases cathepsins B and L. Notably, these two proteases also physically interacted with the corresponding portion of the AAV2 capsid in yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential for efficient AAV2- and AAV8-mediated transduction of mammalian cells, and
Podosomes mediate cell migration and invasion by coordinating the reorganization of actin cytoskeleton and focal matrix degradation. MMP and serine proteases have been found to function at podosomes. The lysosomal cysteine cathepsins, a third major class of matrix-degrading enzymes involved in tumor invasion and tissue remodeling, have yet to be linked to podosomes with the exception of cathepsin K in osteoclasts. Using inhibitors and shRNA-mediated depletion, we show that cathepsin B participates in podosomes-mediated focal matrix degradation and invasion in v-Src-transformed fibroblasts. We observed that lysosomal marker LAMP-1 localized at the center of podosome rosettes protruding into extracellular matrix using confocal microscopy. Time-lapse live-cell imaging revealed that lysosomal vesicles moved to and fused with podosomes. Disruption of lysosomal pH gradient with Bafilomycin A1, chloroquine, or ammonium chloride greatly enhanced the formation of podosomes and increased the matrix degradation.
Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC-NS-629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC-NS-629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment ...
TY - JOUR. T1 - Changes in Activity of Cysteine Cathepsins B and L in Brain Structures of Mice with Aggressive and Depressive-Like Behavior Formed under Conditions of Social Stress. AU - Zhanaeva, S. Ya. AU - Rogozhnikova, A. A.. AU - Alperina, E. L.. AU - Gevorgyan, M. M.. AU - Idov, G. V.. PY - 2018/3/1. Y1 - 2018/3/1. N2 - We studied activity of lysosomal cysteine proteases, cathepsins B and L, in brain structures (frontal cortex, caudate nucleus, hippocampus, and hypothalamus) of C57Bl/6J mice with aggressive and depressive-like behavior formed under conditions of chronic social stress (repeated experience of victories and defeats within 20 days). Mice with depressive-like behavior showed increased activity of cathepsin В in the hypothalamus and nucleus caudatus and increased activity of cathepsin L in the hippocampus compared to control animals not subjected to agonistic confrontations. In mice with aggressive behavior, protease activity in the studied brain structures was not changed. In ...
There is considerable interest in investigating conserved roles for protease in the Hypersensitive Response (HR), a plant defence response which shares some morphological characteristics with apoptosis. a cysteine protease, with homology to mammalian Cathepsin B proteases, was isolated in a screen for genes up-regulated in the HR. The focus of this current research is to examine the roles of Cathepsin B genes in the model plant Arabidopsis. There are three Cathepsin B homologues in Arabidopsis for which knock-out lines were isolated and genetically crossed using a combination of T-DNA insert lines and RNAi to generate double and triple mutants. These genes were found to act redundantly with triple mutants showing increased susceptibility to both virulent and avirulent strains of Pseudomonas syringae DC3000. Moreover, these genes are also involved in non-host resistance to fungal pathogen Blumeria graminis f.sp. tritici, where they positively regulate the HR but negatively regulate ...
Recombinant Human Cathepsin B /CTSB Protein, APP secretase (APPS), belongs to peptidase C1 family, produced in human 293 cells (HEK293).
When hypertonicity is imposed with sufficient intensity and acuteness, cells die. Here we investigated the cellular pathways involved in death using a cell line derived from renal epithelium. We found that hypertonicity rapidly induced activation of an intrinsic cell death pathway- release of cytochrome c and activation of caspase-3 and caspase-9-and an extrinsic pathway-activation of caspase-8. Likewise, a lysosomal pathway of cell death characterized by partial lysosomal rupture and release of cathepsin B from lysosomes to the cytosol was also activated. Relationships among the pathways were examined using specific inhibitors. Caspase inhibitors did not affect cathepsin B release into the cytosol by hypertonicity. In addition, cathepsin B inhibitors and caspase inhibitors did not affect hyper-tonicity-induced cytochrome c release, suggesting that the three pathways were independently activated. Combined inhibition of caspases and cathepsin B conferred significantly more protection from ...
We synthesized one series of fluorogenic substrates for cathepsin B derived from the peptide Bz-F-R-MCA (Bz = benzoyl, MCA = 7-methyl-coumarin amide) substituting Phe at the P(2) position by non-natural basic amino acids that combine a positively charged group with aromatic or aliphatic radicals at the same side chain, namely, 4-aminomethyl-phenylalanine, 4-guanidine-phenylalanine. 4-aminomethyl-N-isopropyl-phenylalanine. 3-pyridyl-alanine, 4-piperidinyl-alanine, 4-amino-methyl-cyclohexyl-alanine. 4-aminocyclohexyl-alanine, and N(im)-dimethyl-histidine. Bz-F-R-MCA was the best substrate for cathepsin B but also hydrolyzed Bz-R-R-MCA with lower efficiency, since the protease accepts Arg at St due to the presence of Glu(245) at the bottom of this subsite. the presence of the basic non-natural amino acids at the Pt position of the substrate partially restored the catalytic efficiency of cathepsin B. All the kinetic parameters for hydrolysis of the peptides described in this paper are in accordance ...
TY - JOUR. T1 - Increased muscle proteolysis after local trauma mainly reflects macrophage-associated lysosomal proteolysis. AU - Farges, M C AU - Balcerzak, Denis Pierre. AU - Fisher, B D AU - Attaix, D AU - Bechet, D AU - Ferrara, M AU - Baracos, V E PY - 2002/2. Y1 - 2002/2. N2 - Rat gastrocnemius showed increased protein degradation (+75-115%) at 48 h after traumatic injury. Injured muscle showed increased cathepsin B activity (+327%) and mRNA encoding cathepsin B (+670%), cathepsin L (+298%), cathepsin H (+159%), and cathepsin C (+268%). In in situ hybridization, cathepsin B mRNA localized to the mononuclear cell infiltrate in injured muscle, and only background levels of hybridization were observed either over muscle cells in injured tissue or in uninjured muscle. Immunogold/electron microscopy showed specific staining for cathepsin B only in lysosome-like structures in cells of the mononuclear cell infiltrate in injured muscle. Muscle cells were uniformly negative in the ...
|p| MDL 28170 is a selective inhibitor, which inhibites calpain with Ki values of 10nM and cathepsin B with Ki values of 25 nM while does not inhibit trypsin-like serine proteases. And it can penetrate the blood-brain barrier rapidly and show the activity
VisEn Medical (VisEn), a provider of fluorescence in vivo imaging from research through medicine, has launched its new Cat B 680 FAST imaging agent. It is meant for measuring and monitoring cathepsin B activity associated with disease progression and therapeutic response in vivo. Cathepsin B expression is a key biomarker and therapeutic target in a range of diseases, including atherosclerosis, oncology, and arthritis. The new agent is designed to complement the companys existing in vivo agent product lines, providing early imaging time points and an additional reporting wavelength for more multiplexing choices in cell-based and in vivo research study designs.. The fluorescence imaging agents and labels are designed to provide a range of biologically-specific imaging readouts in vivo. The company offers over 30 different fluorescence molecular agents for imaging key disease-associated biologic targets, processes and pathways, said the company. The agents are designed for in vivo biomarker ...
3d0g), namely at residues 31, 35, 38, & 353 in ACE2 or residues 479 and 487 in the SARS-CoV RBD, are what allowed for SARS transmission from Civets to Humans. In fact, in those SARS strains which were determined to be most infectious, the unfavorable electrostatic interactions at the binding interface were removed via mutations at the critical residues 479 and 487. [16] In 2020 Zhou et al. (Nature. 2020; 579: 270-273) and Hoffmann et al. (Cell. 2020; 181: 271-280) showed that SARS-CoV-2, the COVID-19 coronavirus causing the global 2019-2020 pandemia, uses ACE2 as a receptor protein to enter and infect cells, just as SARS-CoV does. Cell entry requires the binding of the S1 region of the virus spike (S) protein to ACE2 followed by the fusion of the viral and cellular membranes produced by the S2 subunit of the S protein. Beforehand, this process requires priming of the S protein by host cell proteases, which is performed by TMPRSS2 and the endosomal cysteine proteases cathepsin B and L (CatB/L). ...
Cathepsin B is a lysosomal cysteine protease, which is involved in the degradation of the extracellular matrix in tumor growth. It has been investigated in various carcinomas of the gastrointestinal tract, lung, breast, and others. Correlations with clinico-pathological variables and a worse prognosis associated with a strong expression of cathepsin B have been observed in some studies. However, in gastric cancer, previous results were contradictory. In the present immunohistochemical study, gastric adenocarcinomas from 115 patients were included. All patients were treated by gastrectomy with D2 lymphadenectomy. 49 patients were women (42.6 %) and 66 (57.4 %) were men. The mean age was 64.4 years (range: 33 - 85). All carcinomas were classified according to the UICC, WHO, Laur n, Goseki and Ming classification. Formalin-fixed and paraffin-embedded specimens were immunohistochemically stained according to a standard ABC peroxidase method. The extent of immunoreactivity was scored ...
1CPJ: Crystal structures of recombinant rat cathepsin B and a cathepsin B-inhibitor complex. Implications for structure-based inhibitor design.
Cathepsin B is an enzymatic protein belonging to the peptidase (or protease) families. In humans, it is coded by the CTSB gene. The protein encoded by this gene is a lysosomal cysteine protease composed of a dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. It is a member of the peptidase C1 family. At least five transcript variants encoding the same protein have been found for this gene.
Feminine and Man C57Bl6 mice were fed a control AIN76A diet plan, a fresh Western-style diet plan (NWD1) reflecting diet patterns associated with elevated cancer of the colon incidence (higher body fat, lower cholecalciferol, calcium mineral, methyl donors, fiber), or NWD1 with elevated cholecalciferol and calcium mineral (NWD2) from weaning. and improved serum concentrations from the proinflammatory cytokine IL-1, and of its focuses on, MCP-1 and Rantes, that have been prevented or mitigated in the NWD2 group greatly. However, there is also raised lipid storage space in the liver organ and steatosis not really observed in the control and NWD1 organizations. Thus, elevating calcium mineral and cholecalciferol inside a Western-style diet plan can decrease swelling connected with risk for digestive CGP 60536 tract tumor advancement, but discussion of nutrition in the dietary plan can compromise liver organ function when given long term. Intro Newmark, Lipkin, and co-workers (1C4) designed ...
We develop a simple fluorescence method for the sensitive detection of cathepsin B activity based on the integration of a peptide-DNA conjugate with multiple cyclic signal amplification. This method can detect cathepsin B activity with an extremely low detection limit of 8.1 × 10⁻¹² g mL⁻¹ and a large dynamic range of 4 orders of magnitude from 1 × 10⁻¹¹ to 1 × 10⁻⁷ g mL⁻¹, and it can even measure ...
Sigma-Aldrich offers abstracts and full-text articles by [Soon-Duck Ha, Boram Ham, Jeremy Mogridge, Paul Saftig, Shengcai Lin, Sung Ouk Kim].
CTSB - CTSB (GFP-tagged) - Human cathepsin B (CTSB), transcript variant 5 available for purchase from OriGene - Your Gene Company.
Nanomaterials are being incorporated into many biological applications for use as therapeutics sensors or labels. silver nanoparticles due to the increased use of these materials in biological applications. This manuscript depicts how both of these types of nanomaterials affect cathepsin activity which could impact the hosts immune system and its ability to respond to pathogens. Cathepsin B activity decreases in a dose-dependent manner with all nanoparticles tested. Alternatively the impact of nanoparticles on cathepsin L activity depends greatly on the type and size of the material. ≤ 0.05 was used as the level for significance. A-867744 Results Ag-NP Biocompatibility in Vero cells After a 24-h exposure a 25% decline in cell viability was observed in Vero cells exposed to 50 μg/ml of 10-nm uncoated Ag-NPs Mouse monoclonal to MAP2. MAP2 is the major microtubule associated protein of brain tissue. There are three forms of MAP2; two are similarily sized with apparent molecular weights of 280 ...
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Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged exposure to silica can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here we demonstrate that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3. NALP3 activation required phagocytosis of crystals, and this uptake subsequently led to lysosomal damage and rupture. Sterile lysosomal damage (without crystals) also induced NALP3 activation, and inhibition of either phagosomal acidification or cathepsin B activity impaired NALP3 activation. Our results indicate that the NALP3 inflammasome senses lysosomal damage as an endogenous danger signal.
Polyclonal antibody for Cathepsin B/CTSB detection. Host: Rabbit.Size: 100μg/vial. Tested applications: WB. Reactive species: Human. Cathepsin B/CTSB information: Molecular Weight: 37822 MW; Subcellular Localization: Lysosome. Melanosome. Secreted, extrac
IL-13 dysregulation plays a critical role in the pathogenesis of a variety of inflammatory and remodeling diseases. In these settings, STAT6 is believed to be the canonical signaling molecule mediating the tissue effects of IL-13. Signaling cascades involving MAPKs have been linked to inflammation and remodeling. We hypothesized that MAPKs play critical roles in effector responses induced by IL-13 in the lung. We found that Tg IL-13 expression in the lung led to potent activation of ERK1/2 but not JNK1/2 or p38. ERK1/2 activation also occurred in mice with null mutations of STAT6. Systemic administration of the MAPK/ERK kinase 1 (MEK1) inhibitor PD98059 or use of Tg mice in which a dominant-negative MEK1 construct was expressed inhibited IL-13-induced inflammation and alveolar remodeling. There were associated decreases in IL-13-induced chemokines (MIP-1α/CCL-3, MIP-1β/CCL-4, MIP-2/CXCL-1, RANTES/CCL-5), MMP-2, -9, -12, and -14, and cathepsin B and increased levels of α1-antitrypsin. ...
Traditional mouse models of cancer rely primarily on ex vivo measurements of disease morphology and histologic analysis for the assessment of tumors. These measurements of disease may be distant from the actual biological targets of interest and can be time consuming, expensive, and impractical. By using NIR (Near-Infrared) in vivo imaging probes in combination with FMT, the biological processes that change with disease progression and therapeutic response can be visualized non-invasively over time.. ProSense™ agents were developed to specifically look at the expression and activity of key disease associated proteases. ProSense agents are optically silent until in the presence of these proteases and can be used to easily monitor the activity of these proteases in real time. PerkinElmer offers three different ProSense activatable agents. ProSense 680 is activated by Cathepsin B, L, S and Plasmin. ProSense 750 FAST is activated by Cathepsin B, L, S, K, V and D. ProSense 750 EX is activated by ...
Human CTSB full-length ORF (NP_001899.1, 1 a.a. - 339 a.a.) recombinant protein with GST-tag at N-terminal. (H00001508-P02) - Products - Abnova
Apoptosis, Autophagy, Caspase-3, Cathepsin, Cathepsin B, Cdna, Cell Death, Cysteine, Cytochrome, Cytochrome C, Death, Glycoprotein, Inhibition, Light, Medulloblastoma, Membrane, Microtubule, Mitochondria, Neoplasms, Neuroblastoma
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. Using activity-based probes, we have examined the activity and expression of cysteine cathepsins in a mouse model of breast cancer metastasis to bone. In mice bearing highly metastatic tumors, we detected abundant cysteine cathepsin expression and activity in myeloid-derived suppressor cells (MDSCs). These immature immune cells have known metastasis-promoting roles, including immunosuppression and osteoclastogenesis, and we assessed the contribution of cysteine cathepsins to these functions. Blocking cysteine cathepsin activity with multiple small-molecule ...
Purpose : We have previously demonstrated that an accumulation of advanced glycation end-products (AGEs) in the Bruchs membrane (BrM) can alter retinal pigment epithelium (RPE) lysosomal activity by changing expression of key effectors and inhibitors. Altered activity of lysosomal cysteine proteases, the cathepsins, can in turn impact signalling via the NF-kB pathway. The aim of this study therefore was to analyse the effects of AGEs on specific lysosomal cathepsins, and the endogenous levels of effectors of the NF-kB signalling pathway in RPE. Methods : ARPE-19 cells were cultured on AGE-containing BrM mimics in vitro for 7-14 days. Intracellular processing of the cysteine proteases cathepsins B, L and S were assessed by qPCR and immunoblotting, while their intracellular activity was assessed using fluorescence-based cleavage assays. Expression of NF-kB (p65) and its main regulatory protein, IκBα, was assessed by qPCR and immunoblotting. Statistical analysis was performed using the ...
Cathepsins in general are of interest to parasitologists, as there is considerable evidence that they play a key role in the biology of parasites [29]. In this study, a CB of C. sinensis was cloned and overexpressed in E. coli. It was classified as CB due to its sequence homology to cathepsin B protein and structure. The putative amino acid sequence shared 63%, 52% and 50% identities with cathepsin B from S. japonicum, H. sapiens and F. hepatica, respectively. Sequence analysis showed that Cs CB has typical catalytic residue of cysteine, histidine and asparagine, as well an occluding loop that is the signature of cathepsin Bs [30]. A haemoglobinase motif which is shared by helminth blood-feeders could be found in this deduced sequence [31]. Since C. sinensis generally feed on bile and epithelial cells rather than blood, however, it is thought that this motif may be an important tool for identifying potential hemoglobinases and contribute to haemoglobin degradation [32]. The occluding loop is a ...
1. L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) at a concentration of 0.5 mM had no effect on the serine proteinases plasma kallikrein and leucocyte elastase or the metalloproteinases thermolysin and clostridial collagenase. In contrast, 10 muM-E-64 rapidly inactivated the cysteine proteinases cathepsins B, H and L and papain (t0.5 = 0.1-17.3s). The streptococcal cysteine proteinase reacted much more slowly, and there was no irreversible inactivation of clostripain. The cysteine-dependent exopeptidase dipeptidyl peptidase I was very slowly inactivated by E-64. 2. the active-site-directed nature of the interaction of cathepsin B and papain with E-64 was established by protection of the enzyme in the presence of the reversible competitive inhibitor leupeptin and by the stereospecificity for inhibition by the L as opposed to the D compound. 3. It was shown that the rapid stoichiometric reaction of the cysteine proteinases related to papain can be used to determine the operational molarity of
Complexes of gold( I) have long been used to treat rheumatoid arthritis although the precise biological targets of gold are not well understood. One intriguing therapeutic target of Au( I) is the cathepsin family of lysosomal cysteine proteases. Here, we present the inhibition of cathepsin B by a known Au( I)-based drug and a series of derivatives. The complexes investigated were reversible, competitive inhibitors with IC50 values ranging from 0.3 to 250 mu M, depending on the substituents around the Au( I). ...
Authors: Therese Featherston, Reginald Marsh, Bede van Schaijik, Helen D. Brasch, Swee T. Tan and Tinte Itinteang. Frontiers in Medicine. July 2017. Volume 4, Article 100 doi: 10.3389/fmed.2017.00100. http://journal.frontiersin.org/article/10.3389/fmed.2017.00100/full. The GMRI has previously demonstrated the putative presence of two cancer stem cell (CSC) subpopulations within moderately differentiated oral tongue squamous cell carcinoma (MDOTSCC), which express components of the renin-angiotensin system (RAS).. In this study we investigated the expression and localisation of the proteases cathepsins B, D, and G in relation to these CSC subpopulations within MDOTSCC.. We identified the presence of cathepsins B and D in the CSCs and cathepsin G on what are phenotypically mast cells. The identification of these suggests the presence of bypass loops for the RAS. Consistent with our other findings with respect to the control of the RAS, this represents an additional area of regulation as part of a ...
Compounds of the formula (I), wherein R.sub.1 is aryl or biaryl; R.sub.2 is aryl-lower alkyl, biaryl-lower alkyl, benzo-fused cycloalkyl, cycloalkyl-lower alkyl, bicycloalkyl-lower alkyl, aryloxy-lower alkyl, or aryl-C.sub.2 -C.sub.7 -alkyl in which C.sub.2 -C.sub.7 -alkyl is interrupted by Y; Y is O, S, SO, SO.sub.2, CO or NR.sub.6 ; R.sub.3 is hydrogen or lower alkyl; or R.sub.2 and R.sub.3 combined are C.sub.2 -C.sub.7 -alkylene or C.sub.2 -C.sub.7 -alkylene interrupted by Y; R.sub.4 is hydrogen or lower alkyl; R.sub.5 is hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, biaryl-lower alkyl, cycloalkyl-lower alkyl, bicycloalkyl-lower alkyl, aryloxy-lower alkyl, or aryl-C.sub.2 -C.sub.7 -alkyl in which C.sub.2 -C.sub.7 -alkyl is interrupted by Y; R.sub.6 is hydrogen, lower alkyl or aryl-lower alkyl; and pharmaceutically acceptable salts thereof, which are useful as cysteine cathepsin inhibitors ##STR1##
TY - JOUR. T1 - Role of cathepsin B in the pathogenesis of acute pancreatitis. AU - Gumaste, Vivek V.. PY - 1994/4. Y1 - 1994/4. UR - http://www.scopus.com/inward/record.url?scp=0028301772&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0028301772&partnerID=8YFLogxK. M3 - Article. C2 - 8143984. VL - 106. SP - 1123. EP - 1125. JO - Gastroenterology. JF - Gastroenterology. SN - 0016-5085. IS - 4. ER - ...
Fingerprint Dive into the research topics of Elevated levels of cathepsin B in human glioblastoma cell lines.. Together they form a unique fingerprint. ...
TY - JOUR. T1 - Natively inhibited trypanosoma brucei cathepsin B structure determined by using an x-ray laser. AU - Redecke, Lars. AU - Nass, Karol. AU - DePonte, Daniel P.. AU - White, Thomas A.. AU - Rehders, Dirk. AU - Barty, Anton. AU - Stellato, Francesco. AU - Liang, Mengning. AU - Barends, Thomas R M. AU - Boutet, Sébastien. AU - Williams, Garth J.. AU - Messerschmidt, Marc. AU - Seibert, M. Marvin. AU - Aquila, Andrew. AU - Arnlund, David. AU - Bajt, Sasa. AU - Barth, Torsten B.. AU - Bogan, Michael J.. AU - Caleman, Carl. AU - Chao, Tzu Chiao. AU - Doak, R. Bruce. AU - Fleckenstein, Holger. AU - Frank, Matthias. AU - Fromme, Raimund. AU - Galli, Lorenzo. AU - Grotjohann, Ingo. AU - Hunter, Mark S.. AU - Johansson, Linda C.. AU - Kassemeyer, Stephan. AU - Katona, Gergely. AU - Kirian, Richard A.. AU - Koopmann, Rudolf. AU - Kupitz, Chris. AU - Lomb, Lukas. AU - Martin, Andrew V.. AU - Mogk, Stefan. AU - Neutze, Richard. AU - Shoeman, Robert L.. AU - Steinbrener, Jan. AU - Timneanu, ...
Introduction: The Cathepsins are a group of lysosomal thiol proteinases or endopeptidases found in extracts of various tissues.Cathepsins, with the…
l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as ...
A team of scientists from the University of California, San Diego School of Medicine, the Medical University of South Carolina and San Diego-based American Life Science Pharmaceuticals, Inc., report that cathepsin B gene knockout or its reduction by an enzyme inhibitor blocks creation of key neurotoxic pGlu-Aβ peptides linked to Alzheimers disease. Moreover, the candidate inhibitor drug has been shown to be safe in humans.
Human cysteine cathepsins constitute an 11-membered family of proteases responsible for degradation of proteins in cellular endosomal-lysosomal compartments as such, they play important roles in antigen processing, cellular stress signaling, autophagy, and senescence. Moreover, for many years these …
TY - JOUR. T1 - Cathepsin S Is Involved in Th17 Differentiation Through the Upregulation of IL-6 by Activating PAR-2 after Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis. AU - Dekita, Masato. AU - Wu, Zhou. AU - Ni, Junjun. AU - Zhang, Xinwen. AU - Liu, Yicong. AU - Yan, Xu. AU - Nakanishi, Hiroshi. AU - Takahashi, Ichiro. PY - 2017. Y1 - 2017. N2 - Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4(+) T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions. In the present study, we found that CatS-induced IL-6 production by splenic DCs subsequently promotes Th17 ...
Principal Investigator:KATUNUMA Nobuhiko, Project Period (FY):1989 - 1990, Research Category:Grant-in-Aid for Developmental Scientific Research (B)., Research Field:Pathological medical chemistry
Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study.. ...
Proteomics and at least one of the other two approaches identified a molecular signature of plaques from symptomatic patients that comprised matrix metalloproteinase 9, chitinase 3-like-1, S100 calcium binding protein A8 (S100A8), S100A9, cathepsin B, fibronectin, and galectin-3-binding protein. Biomarker candidates measured in 685 subjects in the Bruneck study were associated with progression to advanced atherosclerosis and incidence of cardiovascular disease over a 10-year follow-up period. A 4-biomarker signature (matrix metalloproteinase 9, S100A8/S100A9, cathepsin D, and galectin-3-binding protein) improved risk prediction and was successfully replicated in an independent cohort, the SAPHIR study.. ...
Antibody Sampler Kit for studying ASC mouse/Axl/Cathepsin B/CD68/galectin-3/HIF1A/HIF1A (Pro564) hydroxylate/HS1 in the Neuroscience research area.
Dumartin, Laurent; Whiteman, Hannah J; Weeks, Mark E; Hariharan, Deepak; Dmitrovic, Branko; Iacobuzio-Donahue, Christine A; Brentnall, Teresa A; Bronner, Mary P; Feakins, Roger M; Timms, John F; +3 more... Brennan, Caroline; Lemoine, Nicholas R; Crnogorac-Jurcevic, Tatjana; (2011) AGR2 is a novel surface antigen that promotes the dissemination of pancreatic cancer cells through regulation of cathepsins B and D. Cancer research, 71 (22). pp. 7091-7102. ISSN 0008-5472 DOI: https://doi.org/10.1158/0008-5472.CAN-11-1367 Full text not available from this repository ...
The AP-1 (activator protein-1) complex, which consists of proteins of the Fos and Jun families, is thought to play an important role in the balance between cell proliferation and apoptosis, the response to genotoxic stress ...
... collagenases such as cathepsin B1; and hyaluronidase. PSGAG inhibits the synthesis of prostaglandin E2, which is released upon ...
Cathepsin E. TALE homeodomain transcription factors. Hydrocortisone. Since keratinocyte differentiation inhibits keratinocyte ... "The role of cathepsin E in terminal differentiation of keratinocytes". Biological Chemistry. 392 (6): 571-85. doi:10.1515/BC. ...
Cathepsin D is involved in CLN10. DNA analysis can be used to help confirm the diagnosis of Batten disease. When the mutation ...
Miv-711 Cathepsin K inhibitor for osteoarthritis. Fast track (FDA) MALT1 "Swedish pharma firm Medivir partners GVK Bio for drug ...
Mediation by cathepsin G has been suggested. The treatment of RAS usually involves administering dexamethasone IV, with the ...
"Cathepsins as transcriptional activators? Developmental Cell 2004, 6(5):610-1. Goulet B, and Nepveu A. "Complete and Limited ...
These cysteine proteases include calpain, caspase, and cathepsin. These three proteins are examples of detectable signs of ...
... α: cathepsin L-like protein in sponge biosilica. Proceedings of the National Academy of Sciences, 95(11), pp.6234- ... Silicateins are homologous to the cysteine protease cathepsin. In sponges, the silicatein enzymes reside in the axial filaments ...
2000). "Secreted cathepsin L generates endostatin from collagen XVIII". EMBO J. 19 (6): 1187-94. doi:10.1093/emboj/19.6.1187. ... 2000). "Secreted cathepsin L generates endostatin from collagen XVIII". EMBO J. 19 (6): 1187-94. doi:10.1093/emboj/19.6.1187. ... by proteases such as cathepsins. Collagen is a component of epithelial and endothelial basement membranes. Endostatin, as a ...
Under the direction of Joseph S. Fruton, Jones' dissertation research involved the catalytic properties of cathepsin C, a type ... She pursued these interests by studying androsterone and monopalmitin at Armour, and cathepsin C at Yale. Jones worked as ... Her doctorate was entitled: Transamidation reactions catalyzed by cathepsin C. Jones completed her studies in three years ... Transamidation Reactions Catalyzed by Cathepsin C. Yale University, 1952. Kresge, Nicole; Simoni, Robert D.; Hill, Robert L. ( ...
... cathepsin G and proteinase 3. Phthalimide derivatives were seen to be inactive, while saccharin derivatives were seen to be ... cathepsin G and proteinase 3". Bioorganic & Medicinal Chemistry. 3 (2): 187-193. doi:10.1016/0968-0896(95)00013-7. PMID 7796053 ...
In humans, the group of cathepsin cysteine proteases or cysteine cathepsins comprises 11 family members, cathepsins B, C, F, H ... Examination of cathepsin activity by using chemical probes and in vivo imaging techniques demonstrated an increase in cathepsin ... Cathepsins also can be secreted by cells, associate with the cell surface, and degrade the ECM. A study of all 11 members of ... Cathepsin L is active at neutral pH by associating with a p41 splice variant of the MHC class II-associated invariant chain ...
They are also members of the cathepsin family and can digest lysosomes. Cry6Aa triggers a magnesium dependent adenylyl cyclase/ ...
Hook G, Yu J, Toneff T, Kindy M, Hook V. "Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the ... Kumar P, Nachagari D, Fields C, Franks J, Albritton LM (October 2007). "Host cell cathepsins potentiate Moloney murine leukemia ... reduces brain amyloid-β and improves memory deficits in Alzheimer's disease animal models by inhibiting cathepsin B, but not ... and Structure-Activity Relationship Study of Epoxysuccinyl-Peptide Derivatives as Cathepsin B Inhibitors". Biological & ...
Of these hydrolytic enzymes, cathepsin K is of most importance. Cathepsin K and other cathepsins[edit]. Cathepsin K is a ... Several other cathepsins are expressed in osteoclasts including cathepsins B, C, D, E, G, and L. The function of these cysteine ... characterised by a lack of functional cathepsin K expression. Knockout studies of cathepsin K in mice lead to an osteopetrotic ... Studies on cathepsin L knockout mice have been mixed, with a report of reduced trabecular bone in homozygous and heterozygous ...
2002). "Evidence that E-box promoter elements and MyoD transcription factors play a role in the induction of cathepsin B gene ... They act by transactivating cathepsin B promotor activity and inducing its mRNA expression. E47 is produced by alternative ...
Cathepsin, Lectin. The Bathini Goud Brothers in Hyderabad, India, promote the swallowing of live murrel fish and herbs as an ... cathepsin L: bioinformatics characterization, gene expression and proteolytic activity". Biologia. 39 (3): 395-406. doi:10.2478 ...
SDF stops the degradation of cysteine cathepsins, which are also responsible for dentine collagen degradation. A systematic ... "The inhibitory effects of silver diamine fluorides on cysteine cathepsins". primary. Journal of Dentistry. 42 (3): 329-35. doi: ...
Cathepsin S which is produced by most of the antigen- presenting cells along with mTECs is absent in cTECs. Cathepsin L not ... MHC II processing and presentation in cTECs took advantage of several proteolytic pathways including cathepsin L, encoded by ... Honey, Karen; Nakagawa, Terry; Peters, Christoph; Rudensky, Alexander (2002-05-20). "Cathepsin L Regulates CD4+ T Cell ... "Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus". Science. 280 (5362): 450-453. doi:10.1126 ...
"Early immunodiagnosis of fasciolosis in ruminants using recombinant Fasciola hepatica cathepsin L-like protease". International ...
"Table 1: The Single Nucleotide Polymorphisms in cathepsin B protein mined from literature (PMID: 16492714)". dx.doi.org. doi: ...
These markers include angiotensin-converting enzyme, cathepsin S, chitotriosidase, and CCL18 in the blood plasma; and tumor ...
... and cathepsin D. Cathepsin D has been proposed as the main target for ceramide formed in organelles called lysosomes, making ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ...
p-ANCA without nuclear extension occurs with antibodies to BPI, cathepsin G, elastase, lactoferrin and lysozyme. GS-ANA are ...
1997). "Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas". Invest. ...
Studies showed that adducts form between RAPTA compounds and proteins (especially cathepsin B and thioredoxin reductase(TrxR ... inhibition of thioredoxin reductase and cathepsin B by antitumor ruthenium(II)-arene compounds". J. Med. Chem. 54: 6773-6781. ...
A cysteine peptidase cathepsin B1 of T. regenti (TrCB1) localised in intestines of migrating schistosomula is capable of myelin ... "Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti: identification, characterisation and putative role ... Experiments with laboratory prepared recombinant form of the cysteine peptidase cathepsin B2 of T. regenti (TrCB2) confirmed ...
"Molecular cloning and analysis of stage and tissue-specific expression of cathepsin B encoding genes from Fasciola gigantica". ...
"Requirement of the human GARP complex for mannose 6-phosphate-receptor-dependent sorting of cathepsin D to lysosomes". ...
These include lactoferrin, elastase, and cathepsin G. When the condition is a vasculitis, the target is usually MPO. However, ...
Cathepsin: Cathepsins ( Ancient Greek kata- "down" and hepsein "boil"; abbreviated CTS ) are proteases ( enzymes that degrades ... Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption. They degrade polypeptides and are ... There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone ...
Cathepsin A (serine protease) Cathepsin B (cysteine protease) Cathepsin C (cysteine protease) Cathepsin D (aspartyl protease) ... Cathepsin H (cysteine protease) Cathepsin K (cysteine protease) Cathepsin L1 (cysteine protease) Cathepsin L2 (or V) (cysteine ... Cathepsin S (cysteine protease) Cathepsin W (cysteine proteinase) Cathepsin Z (or X) (cysteine protease) Cathepsins have been ... Cathepsin K has also been shown to play a role in arthritis. Mouse cathepsin L is homologous to human cathepsin V. Mouse ...
Cathepsin T (EC 3.4.22.24) is an enzyme. This enzyme catalyses the following chemical reaction Interconversion of the three ... Cathepsin Gohda E, Pitot HC (May 1981). "Purification and characterization of a new thiol proteinase from rat kidney". ... Cathepsin+T at the US National Library of Medicine Medical Subject Headings (MeSH) Biology portal. ... Pitot HC, Gohda E (1987). "Cathepsin T". Methods in Enzymology. 142: 279-89. doi:10.1016/s0076-6879(87)42038-7. PMID 2885716. ...
"Human cathepsins W and F form a new subgroup of cathepsins that is evolutionary separated from the cathepsin B- and L-like ... Wex T, Levy B, Wex H, Brömme D (1999). "Human cathepsins F and W: A new subgroup of cathepsins". Biochem. Biophys. Res. Commun ... 2003). "Characterization of novel anti-cathepsin W antibodies and cellular distribution of cathepsin W in the gastrointestinal ... Cathepsin W is a protein that in humans is encoded by the CTSW gene.[5][6][7] ...
"Entrez Gene: CTSD cathepsin D".. *^ Barrett AJ (April 1970). "Cathepsin D. Purification of isoenzymes from human and chicken ... Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes.[7] The main function of cathepsin D is ... The optimum pH for cathepsin D in vitro is 4.5-5.0.[13] Cathepsin-D is an aspartic protease that depends critically on ... Cathepsin D is a protein that in humans is encoded by the CTSD gene.[5][6] This gene encodes a lysosomal aspartyl protease ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
If you know of any papers that use this antibody, please contact us at antibodies [at] alzforum [dot] org for consideration in the References section.. ...
cathepsin K. Names. cathepsin O. cathepsin O1. cathepsin O2. cathepsin X. NP_000387.1. *EC 3.4.22.38 ... Metabolic mapping showed that cathepsin B, but not cathepsin K is active in GSC niches. Title: Cysteine cathepsins B, X and K ... cathepsin K in the development of chronic subdural hematoma Title: Role of cathepsin K in the development of chronic subdural ... Cathepsin K degradation of sclerostin is affected by hypoxia. Title: The regulation of sclerostin by cathepsin K in periodontal ...
Cathepsin B. A. 266. Homo sapiens. Mutation(s): 3 Gene Names: CTSB, CPSB. EC: 3.4.22.1. ... Cathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique ... Cathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique ... The chagasin-cathepsin B complex provides a structural framework for modeling and design of inhibitors for cruzipain, the ...
Incubation with the cathepsin L specific inhibitor, Z-FY-DMK, blocked cathepsin L signals, confirming the cathepsin L bands in ... Z-FY-DMK cathepsin L inhibitor does not inhibit all cathepsin activity of murine endometriotic lesions. Incubation with Z-FY- ... DMK, a selective inhibitor of cathepsin L, inhibited many of the cathepsin active bands but did not block all active cathepsin ... E-64 blocks all cathepsin proteolytic activity in murine endometriotic lesions. Incubation with the broad cathepsin inhibitor, ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
V. Zavanik-Bergant, A. Sekirnik, R. Golouh, V. Turk, and J. Kos, "Immunochemical localisation of cathepsin S, cathepsin L and ... Both stimulants caused a significant cathepsin S upregulation. A significantly elevated cathepsin S expression in gingival ... Role of Cathepsin S in Periodontal Inflammation and Infection. S. Memmert,1,2 A. Damanaki,1 A. V. B. Nogueira,3 S. Eick,4 M. ... "Antimicrobial peptide LL-37 is both a substrate of cathepsins S and K and a selective inhibitor of cathepsin L," Biochemistry, ...
Cathepsin K degrades both collagen and elastin, and is one of the most powerful proteases. Cathepsin S degrades elastin, and ... "We saw that the cathepsin K was going away much faster when there was cathepsin S present than when it was by itself," said ... "We kept increasing the amount of cathepsin S until the collagen was not affected at all because all of the cathepsin K was ... Barrys modeling suggested that effects observed could occur if cathepsin S were degrading cathepsin K instead of attacking the ...
The cathepsin S protease is implicated in generation of chronic pain by releasing a cytokine. ... The cathepsin S protease is implicated in generation of chronic pain by releasing a cytokine. ...
Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Graham Simmons, Dhaval N. Gosalia, ... Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Graham Simmons, Dhaval N. Gosalia, ... Cathepsin-L-specific inhibitor blocks infection. (A) MDL28170 inhibits CTSL activity with an IC50 of 2.5 nM. A 1,000-compound ... Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry Message Subject (Your Name) has sent you ...
A direct immunohistochemical method of high specificity is presented for the demonstration of sites of cathepsin B1. Antisera ... Snellman, O.: Cathepsin B, the lysosomal thiol proteinase of calf liver. Biochem. J. 114, 673-678 (1969)Google Scholar ... Otto, K.: Cathepsins B1 and B2. In: Tissue proteinases, ed. by A. J. Barrett and J. T. Dingle, p. 1-28. North-Holland ... V. Cathepsin B as a potential effector of LNA hydrolysis. Histochemie 12, 240-243 (1968)Google Scholar ...
Cathepsin S is a cysteine protease highly expressed in many type of cancers including colorectal, prostate, breast, and ... This mini-review provides an overview of therapeutic antibody targeting Cathepsin S strategies in the last half decade, ... In recent years, antibody research specifically targeting Cathepsin S to block/inhibit tumorigenic effects were generated some ... focusing on the rationale of cell-surface Cathepsin S targeted and their potential clinical application. ...
Rabbit polyclonal Cathepsin E antibody. Validated in WB, IHC, ICC/IF and tested in Mouse, Rat, Human. Cited in 3 publication(s ... Anti-Cathepsin E antibody (ab36996) at 1/1000 dilution + Murine reticulocyte lysate at 10 µg. Predicted band size: 42 kDa. ... High Expression of Cathepsin E in Tissues but Not Blood of Patients with Barretts Esophagus and Adenocarcinoma.. Ann Surg ... Cathepsin E is expressed abundantly in the stomach, Clara cells and alveolar macrophages of the lung, brain microglia, spleen, ...
Rabbit polyclonal Cathepsin D antibody validated for WB, ELISA, IHC, ICC/IF and tested in Human. Referenced in 1 publication ... This antibody reacts with human liver cathepsin D, and does not react with cathepsins B, H and L. ... IHC image of Cathepsin D staining in Human Lung formalin fixed paraffin embedded tissue section, performed on a Leica Bond™ ... Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Cathepsin D antibody (ab19555) ...
... administration of rat recombinant cathepsin B and rat recombinant cathepsin L at the same or higher doses than rrCatS had no ... Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Anna K. Clark, Ping K. Yip, John Grist, Clive ... cathepsin S;. rrCatS,. rat recombinant CatS;. LHVS,. morpholinurea-leucine-homophenylalanine-vinyl phenyl sulfone;. PNL,. ... Here, we report that in peripheral nerve-injured rats, the lysosomal cysteine protease cathepsin S (CatS) is critical for the ...
Protease activity Apolipoprotein A-I Aortic valve stenosis Cathepsin S C. Gebhard and F. Maafi contributed equally to this work ... Hooshdaran B, Kolpakov MA, Guo X, Miller SA, Wang T, Tilley DG, Rafiq K, Sabri A (2017) Dual inhibition of cathepsin G and ... Lindstedt L, Lee M, Oorni K, Bromme D, Kovanen PT (2003) Cathepsins F and S block HDL3-induced cholesterol efflux from ... Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease. ...
Cathepsin B. Cathepsin B, EC 3.4.22.1 (APP secretase, APPS) (Cathepsin B1) [Cleaved into: Cathepsin B light chain; Cathepsin B ... Cathepsin BImported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/ ... tr,E9PL32,E9PL32_HUMAN Cathepsin B (Fragment) OS=Homo sapiens OX=9606 GN=CTSB PE=1 SV=2 ...
Cathepsin GAdd BLAST. ›26. Proteomic databases. PaxDb, a database of protein abundance averages across all three domains of ... sp,P17977,CATG_RAT Cathepsin G (Fragment) OS=Rattus norvegicus GN=Ctsg PE=1 SV=1 IIGGREARPNSHPYMAFLLIQSPEGL ...
MAGIC RED® CATHEPSIN B KIT. A fluorogenic test kit for Cathepsin B. (Patent# 6,235,493-May 22, 2001). Ref.: 1. Van Noorden, C.J ... MAGIC RED® CATHEPSIN K KIT. A fluorogenic test kit for Cathepsin K. (Patent# 6,235,493-May 22, 2001). Ref.: 1. Van Noorden, C.J ... MAGIC RED® CATHEPSIN L KIT. A fluorogenic test kit for Cathepsin L. (Patent# 6,235,493-May 22, 2001). Ref.: 1. Van Noorden, C.J ...
Cathepsin K Polyclonal Antibody from Invitrogen for Western Blot, Immunohistochemistry (Paraffin) and Flow Cytometry ... Protein Aliases: Cathepsin K; Cathepsin O; cathepsin O1; Cathepsin O2; Cathepsin X; CTSK; CTSO; CTSO2 ... Cite Cathepsin K Polyclonal Antibody. The following antibody was used in this experiment: Cathepsin K Polyclonal Antibody from ...
Although a lysosomal, cathepsin B-dependent (Ctsb-dependent) pathway of apoptosis has been described, the contribution of this ...
C.-S. Hsieh, P. DeRoos, K. Honey, C. Beers, and A. Y. Rudensky, "A role for cathepsin L and cathepsin S in peptide generation ... J. Ärnlv, "Cathepsin S as a biomarker: where are we now and what are the future challenges?" Biomarkers in Medicine, vol. 6, no ... Inhibition of Cathepsin S Produces Neuroprotective Effects after Traumatic Brain Injury in Mice. Jianguo Xu,1 Handong Wang,1 Ke ... D. M. Small, R. E. Burden, and C. J. Scott, "The emerging relevance of the cysteine protease cathepsin S in disease," Clinical ...
Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. These data suggest that cad-1 is a ... Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans.. L A Jacobson, L Jen-Jacobson, J M ... Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans.. L A Jacobson, L Jen-Jacobson, J M ... Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans.. L A Jacobson, L Jen-Jacobson, J M ...
CATHEPSIN L-HUMAN LIVER. Cathepsin L is unstable at neutral pH, but is relatively stable in the range 4.5 to 5.5.. ...
Distribution of cathepsin L in human umbilical cord tissues.. [Tomasz Gogiel, Małgorzata Wolańska, Zofia Galewska, Piotr ... The active cathepsin L activity (without activation by pepsin digestion), its percentage in the total activity (after pepsin ... Cathepsin L activity and anti-papain inhibitory effect of cysteine protease inhibitors were quantified in extracts of separated ... Cathepsin L is a potent cysteine protease engaged in degradation of extracellular matrix proteins, including collagens. We ...
  • We hypothesize that cysteine cathepsins, a group of powerful extracellular matrix proteases, facilitate endometrial tissue invasion and endometriosis lesion establishment in the peritoneal wall and inhibiting this activity would decrease endometriosis lesion implantation. (nih.gov)
  • Intraperitoneal injection of the broad cysteine cathepsin inhibitor, E-64, significantly reduced the number of attached endometriosis lesions in our murine model compared to vehicle-treated controls demonstrating that cathepsin proteases contribute to endometriosis lesion establishment, and their inhibition may provide a novel, nonhormonal therapy for endometriosis. (nih.gov)
  • Dubbed "cathepsin cannibalism," the phenomenon may help explain problems with drugs that have been developed to inhibit the effects of these powerful proteases. (innovations-report.com)
  • Cathepsin K degrades both collagen and elastin, and is one of the most powerful proteases. (innovations-report.com)
  • There is growing recognition that alternative proteolytic enzymes such as the lysosomal cathepsin proteases may initiate or propagate proapoptotic signals, but it is currently unclear how cathepsins mediate apoptosis. (biovision.com)
  • Lysosomes contain many well-characterized proteases, and cathepsin B has previously been utilized to release chemotherapeutics in the context of targetable antibody-based treatments. (bloodjournal.org)
  • SerpinB1 is a potent inhibitor of neutrophil serine proteases neutrophil elastase (NE) and cathepsin G (CG). (bloodjournal.org)
  • 6 , 7 Interestingly, noncaspase cysteine proteases calpain and cathepsin D were reported to induce PMN apoptosis through activation of caspases. (bloodjournal.org)
  • 8 ⇓ ⇓ - 11 In addition, PMNs carry a unique set of serine proteases (neutrophil serine proteases [NSPs]) including elastase (NE), cathepsin G (CG), and proteinase-3 (PR3) stored active in primary granules. (bloodjournal.org)
  • In this review we discuss recent advances addressing the role of lysosomal proteases in the diverse aspects of the immune response, and also the involvement of cathepsins in the pathogenesis of diseases in which these proteases seem not to be properly under control. (smw.ch)
  • Cathepsin B is an ancient family of eukaryotic cysteine proteases. (apsnet.org)
  • Our findings provide evidence for the highly specialized functions of closely related cysteine cathepsin proteases in extra-embryonic development, and reinforce their importance for a successful outcome of pregnancy. (biologists.org)
  • Two of the genes identified from this screen were the cathepsin proteases Cts7 and Cts8 . (biologists.org)
  • Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. (semanticscholar.org)
  • Cathepsins are lysosomal proteases that breakdown peptide bonds linked to specific amino acids. (frontiersin.org)
  • Cathepsin B is the first described member of the family of lysosomal cysteine proteases. (neuromics.com)
  • Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. (mdpi.com)
  • Though cytokines and phagocyte, as host factors, have been shown to participate in defence against Aspergillus species yet the role of cysteine proteases, that is cathepsins, a lysosomal enzymes of phagocytes, remains unknown in fungal infection. (ijpsonline.com)
  • Cathepsins are cysteine proteases, act as endopeptidases and are mainly involved in intracellular protein degradation and involved in large number of diseases [ 11 , 12 ]. (ijpsonline.com)
  • Cathepsins B and L are involved in matrix degradation and cell invasion. (wikipedia.org)
  • Cathepsin K, among other cathepsins, plays a role in cancer metastasis through the degradation of the extracellular matrix. (wikipedia.org)
  • The main physiological functions of cathepsin D consist of metabolic degradation of intracellular proteins, activation and degradation of polypeptide hormones and growth factors , activation of enzymatic precursors, processing of enzyme activators and inhibitors, brain antigen processing and regulation of programmed cell death . (wikipedia.org)
  • Using a combination of modeling and experiments, researchers from the Georgia Institute of Technology and Emory University have shown that one type of cathepsin preferentially attacks another, reducing the enzyme's degradation of collagen. (innovations-report.com)
  • When the researchers combined the two cathepsins and allowed them to attack samples of elastin, they expected to see increased degradation of the protein. (innovations-report.com)
  • That theoretical result led to additional experiments in which the researchers measured a direct correlation between an increase in the amount of cathepsin S added to the experiment and a reduction in the degradation of collagen. (innovations-report.com)
  • Cathepsin L is a potent cysteine protease engaged in degradation of extracellular matrix proteins, including collagens. (sigmaaldrich.com)
  • cathepsin H Inhibitors offered by Santa Cruz inhibit cathepsin H and, in some cases, other cellular metabolism and protein degradation related proteins. (scbt.com)
  • Collectively, these results identify an intracellular role for cathepsin B in matrix degradation. (aacrjournals.org)
  • The experimental evidence indicates that a cathepsin B-like enzyme may be partly responsible for the autolytic degradation of cartilage matrix at pH5. (biochemj.org)
  • Cathepsin D is the lysosomal protease in the retinal pigment epithelium which is presumed to be the major enzyme involved in the degradation of shed discs during the photoreceptor renewal process. (arvojournals.org)
  • This antibody is specific for Cathepsin E. (abcam.com)
  • This antibody reacts with human liver cathepsin D, and does not react with cathepsins B, H and L. (abcam.com)
  • The following antibody was used in this experiment: Cathepsin K Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-14270, RRID AB_2087668. (thermofisher.com)
  • This antibody reacts with the zymogen as well as the activated form of cathepsin D. It stains fibroblasts and macrophages strongly but stains the myoepithelial cells of breast weakly. (novusbio.com)
  • Cathepsin D Polyclonal antibody specifically detects Cathepsin D in Human, Mouse, Rat samples. (fishersci.com)
  • Cathepsin 6 Monoclonal antibody specifically detects Cathepsin 6 in Mouse samples. (fishersci.com)
  • Cathepsin B may function as a beta-secretase 1, cleaving amyloid precursor protein to produce amyloid beta. (wikipedia.org)
  • Osteoclasts are the bone resorbing cells of the body, and they secrete cathepsin K in order to break down collagen, the major component of the non-mineral protein matrix of the bone. (wikipedia.org)
  • Cathepsin W is a protein that in humans is encoded by the CTSW gene . (wikipedia.org)
  • Cathepsin D is a protein that in humans is encoded by the CTSD gene . (wikipedia.org)
  • To clarify the mode by which natural protein inhibitors manage to overcome this obstacle, we have analyzed the structure and function of cathepsin B in complexes with the Trypanosoma cruzi inhibitor, chagasin. (rcsb.org)
  • Incubation with the broad cathepsin inhibitor, E-64, completely abolished cathepsin activity detected by zymography identifying the active bands as cysteine cathepsins (A). Cathepsin protein levels in lesions were compared to eutopic uterine tissue by Western blot (B, n = 6). (nih.gov)
  • Cathepsin S was upregulated most strongly and thus further studied in vitro at gene and protein levels. (hindawi.com)
  • Barry's modeling suggested that effects observed could occur if cathepsin S were degrading cathepsin K instead of attacking the elastin - a protein essential in arteries and the cardiovascular system. (innovations-report.com)
  • H. Phipps-Yonas, V. Semik, and K. T. Hastings, "GILT expression in B cells diminishes cathepsin S steady-state protein expression and activity," European Journal of Immunology , vol. 43, no. 1, pp. 65-74, 2013. (hindawi.com)
  • Zusätzlich bieten wir Ihnen Cathepsin A Proteine (28) und Cathepsin A Kits (27) und viele weitere Produktgruppen zu diesem Protein an. (antikoerper-online.de)
  • Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 beta-galactosidase (beta-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. (antikoerper-online.de)
  • Additionally we are shipping Cathepsin D Antibodies (347) and Cathepsin D Proteins (55) and many more products for this protein. (antibodies-online.com)
  • Cathepsin H is a disulfide-linked heavy and light chain dimer which belongs to the peptidase C1 protein family, can act both as an aminopeptidase and as an endopeptidase. (scbt.com)
  • After 4 days of diabetes, cathepsin B and L activities were decreased by 15-45% when correlated with the levels of glomerular protein or DNA. (diabetesjournals.org)
  • Cathepsin D is an estrogen-regulated protein associated with tissue breakdown. (genetex.com)
  • Partially purified Cathepsin B protein was inhibited by a variety of peptide inhibitors but evidence of inhibition by several pathogen-derived inhibitors that are secreted during infection was inconclusive. (bl.uk)
  • Mechanistic studies indicated that the absence of CatL reduced lesion chemokine monocyte chemotactic protein-1 content, macrophage and T-cell in vitro transmigration, and angiogenesis, and altered the expression and activities of matrix metalloproteinases and other cysteinyl cathepsins in inflammatory cells, vascular cells, and AAA lesions. (harvard.edu)
  • Active cathepsins, cathepsin inhibitors and cathepsin antibodies are also available. (biovision.com)
  • 75 Cathepsin S (CTSS) Antibodies from 18 manufacturers are available on www.antibodies-online.com. (antibodies-online.com)
  • On www.antibodies-online.com are 88 Cathepsin D (CTSD) ELISA Kits from 20 different suppliers available. (antibodies-online.com)
  • Over-expression of cathepsin D stimulates tumorigenicity and metastasis as well as initiation of tumor apoptosis. (wikipedia.org)
  • [21] [22] Knock-out of CTSD gene would cause intestinal necrosis and hemorrhage and increase apoptosis in thymus , indicating that cathepsin D is required in certain epithelial cells for tissue remodeling and renewal. (wikipedia.org)
  • Although a lysosomal, cathepsin B-dependent (Ctsb-dependent) pathway of apoptosis has been described, the contribution of this pathway to tissue damage remains unclear. (jci.org)
  • Schwartz-Roberts, Shajahan, Cook, Wärri, Abu-Asab, Clarke: GX15-070 (obatoclax) induces apoptosis and inhibits cathepsin D- and L-mediated autophagosomal lysis in antiestrogen-resistant breast cancer cells. (antibodies-online.com)
  • This suggests that cathepsin D exerts its apoptosis-stimulating effect upstream of caspase-3-like activation. (diva-portal.org)
  • Five cyclic peptides show inhibitory activity towards human cathepsins L, B, H, and K. Zymography is a type of gel electrophoresis that uses a polyacrylamide gel co-polymerized with a substrate in order to detect enzyme activity. (wikipedia.org)
  • Cathepsin T (EC 3.4.22.24) is an enzyme. (wikipedia.org)
  • The researchers used a variety of tests to determine the amount of each enzyme, including fluorogenic substrate analysis, Western blotting and multiplex cathepsin zymography - a sensitive technique developed in the Platt laboratory. (innovations-report.com)
  • Beyond demonstrating for the first time that cathepsins can attack one another, the research also shows the complexity of the body's enzyme system - and may suggest why drugs designed to inhibit cathepsins haven't worked as intended. (innovations-report.com)
  • Cathepsin D purified from a mutant strain has a lower activity per unit mass of pure enzyme. (genetics.org)
  • The active cathepsin L activity (without activation by pepsin digestion), its percentage in the total activity (after pepsin activation), and the expression of the mature single-chain enzyme were the lowest in the umbilical cord arteries and the highest in Wharton's jelly. (sigmaaldrich.com)
  • A Novel Dual Fluorochrome Near-Infrared Imaging Probe for Potential Alzheimer's Enzyme Biomarkers-BACE1 and Cathepsin D. Molecules. (harvard.edu)
  • As cathepsin D activity is increased by cigarette smoke, the enzyme may contribute to lung tissue damage in smokers. (genetex.com)
  • We offer various assays to detect and quantify cathepsin, calpain and granzyme B activity and screen for respective enzyme inhibitors. (promocell.com)
  • Cathepsin D was released from lysosomes to the cytosol upon exposure to naphthazarin, and the enzyme activity decreased simultaneously. (diva-portal.org)
  • Later, cathepsin D reappeared in granules of increased size, and enzyme activity was restored. (diva-portal.org)
  • Lysosomal serine carboxypeptidase Cathepsin A (CTSA) is a multifunctional enzyme with distinct protective and catalytic function. (frontiersin.org)
  • Herein, we describe the preparation of a fused silica capillary, cathepsin D (CatD)-immobilized enzyme reactor (IMER) using in a multidimensional High Performance Liquid Chromatography-based method (2D-HPLC) and zonal affinity chromatography as an alternative in the search for new ligands. (ovid.com)
  • The prodrug demonstrates enzyme-responsive drug release features, and over 95% GEM was released from the carrier with the Cathepsin B within 3 h. (rsc.org)
  • The presence of a cathepsin B-like enzyme in rabbit ear cartilage was established by the use of the synthetic substrates benzoyl- l -arginine amide and benzoyl- dl -arginine 2-naphthylamide. (biochemj.org)
  • The enzymic properties of cathepsin B in cartilage have been compared with an endogenous enzyme that liberates chondromucopeptide by degrading the cartilage matrix autocatalytically at pH5. (biochemj.org)
  • It was catalytically active, as demonstrated by active-site-directed radioiodination, and hydrolysed three cathepsin B substrates, two with Km values similar to those of lysosomal cathepsin B. In addition, the rates of inactivation of the sputum and lysosomal forms of the enzyme by L-3-carboxy-2,3-transepoxypropionyl-leucylamido(4-guanidino) butane (Compound E-64) were very similar. (portlandpress.com)
  • However, the sputum enzyme differed from lysosomal cathepsin B in the following respects. (portlandpress.com)
  • Inhibition by chicken cystatin was much weaker for sputum cathepsin B than for the lysosomal enzyme. (portlandpress.com)
  • There were many hurdles in the drug discovery of cathepsin K inhibitors such as species differences not only in bone metabolism but also in amino acid sequences in the critical site of the target enzyme, discrepancies between PK/PD due to unique tissue distribution of the inhibitor affecting both efficacy and side effects originated from a characteristic intracellular or tissue distribution of some classes of compounds. (eurekaselect.com)
  • The cathepsin K inhibitor drug discovery was initiated based on a strong and osteoclast-specific expression of this enzyme. (eurekaselect.com)
  • The data suggest that the higher levels of cathepsin D activity observed in the freshly isolated RPE from the area centralis result from modulators of enzyme activity which are not present in culture. (arvojournals.org)
  • This review sought to evaluate recent findings in this field, highlighting how among cathepsins, the inhibition of cathepsin S in particular, could play a significant role in diminishing the effects of CVD, especially for patients with CKD. (frontiersin.org)
  • Spi2A defects were ameliorated by cathepsin-B/L inhibition, and by genetic co-deletion of lysosomal cathepsin B. Pharmacological inhibition of cathepsin B/L enhanced EPO-induced red cell formation in normal mice. (rupress.org)
  • A composite docking approach for the identification and characterization of ectosteric inhibitors of cathepsin K. Law S, et al . (nih.gov)
  • 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. (oregonstate.edu)
  • Osteocytes express genes required in osteoclasts for bone resorption, including cathepsin K (Ctsk), and lactation elevates their expression. (jci.org)
  • Cysteine cathepsins belong to the papain-like family C1 of clan CA cysteine peptidases. (nih.gov)
  • 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. (nih.gov)
  • Proteolytic actions performed by cysteine cathepsins are essential in the maintenance of homeostasis and depend heavily upon their correct sorting and trafficking within cells. (nih.gov)
  • 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. (nih.gov)
  • 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. (springer.com)
  • Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption. (genenames.org)
  • Cathepsin K is the most potent mammalian collagenase. (wikipedia.org)
  • Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. (ahajournals.org)
  • The collagenolytic activity of cathepsin K is unique among mammalian proteinases. (semanticscholar.org)
  • Human AAA lesions express high levels of cathepsin L (CatL), one of the most potent mammalian elastases. (harvard.edu)
  • 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. (aacrjournals.org)
  • 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. (aacrjournals.org)
  • 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. (portlandpress.com)
  • Elevated levels of cathepsin H correlates with malignant progression of prostate tumors. (scbt.com)
  • Levels of cathepsin D have been positively correlated with recurring breast cancers of both node negative and node positive types. (genetex.com)
  • Identification of a putative structural gene for cathepsin D in Caenorhabditis elegans. (genetics.org)
  • These data suggest that cad-1 is a structural gene for cathepsin D. (genetics.org)
  • 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. (antibodies-online.com)
  • 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. (inria.fr)
  • 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 ). (bl.uk)
  • Cathepsin K associates with lymph node metastasis and poor prognosis in oral squamous cell carcinoma. (nih.gov)
  • Elevated Cathepsin K potentiates metastasis of epithelial ovarian cancer. (nih.gov)
  • Cathepsins are involved in disease processes as varied as cancer metastasis, atherosclerosis, cardiovascular disease, osteoporosis and arthritis. (innovations-report.com)
  • Involvement of cathepsins in the invasion, metastasis and proliferation of cancer cells. (wikidoc.org)
  • Cathepsin B is among the candidate proteinases believed to participate in invasion and metastasis. (aacrjournals.org)
  • Besides caspases, cathepsins have recently been shown to be associated with cell death regulation [6-12] and various other physiological and pathological processes, such as maturation of the MHC class II complex, bone remodelling, keratinocyte differentiation, tumour progression and metastasis, rheumatoid arthritis and osteoarthritis, as well as atherosclerosis [13, 14] (table 1). (smw.ch)
  • Auf www.antikoerper-online.de finden Sie aktuell 344 Cathepsin D (CTSD) Antikörper von 36 unterschiedlichen Herstellern. (antikoerper-online.de)
  • The purpose of the research reported herein was to develop procedures for the purification of the cathepsin from salmon muscle. (oregonstate.edu)
  • It was decided to attempt the purification of the cathepsin optimally active at pH 3.7. (oregonstate.edu)
  • The purification was accomplished by extracting the salmon muscle cathepsin with two parts 0.2 N KC1. (oregonstate.edu)
  • The purification of cathepsin D from pig uterus by two-step affinity chromatography on concanavalin A- and pepstatin-Sepharose was described previously [Afting & Becker (1981) Biochem. (biochemj.org)
  • Cathepsins are intracellular proteinases that hydrolyze the peptide bonds of proteins. (oregonstate.edu)
  • Surprisingly, at a concentration of 10 μ m , CA-074 slowly permeated the cells, causing an 80-95% inhibition of intracellular cathepsin B after 12 h, the duration of the invasion assay. (aacrjournals.org)
  • The membrane-permeant cathepsin B inhibitor, CA-074 methyl ester, and the higher concentration of CA-074 that inhibited intracellular cathepsin B both significantly reduced Matrigel invasion. (aacrjournals.org)
  • Here, we describe how intracellular sigma peptide modulation of RPTPσ induces enhanced protease Cathepsin B activity. (jneurosci.org)
  • 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. (pnas.org)
  • 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 ). (pnas.org)
  • 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. (hindawi.com)
  • Mutants of Caenorhabditis elegans having about 10% of wild-type activity of the aspartyl protease cathepsin D have been isolated by screening. (genetics.org)
  • 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 ). (jimmunol.org)
  • Serine protease inhibitor serpinB1 protects neutrophils by inhibition of their own azurophil granule protease cathepsin G. (bloodjournal.org)
  • The protease cathepsin D is one such target involved in several diseases such as tumors, degenerative processes, and vital processes of parasites causing schistosomiasis. (ovid.com)
  • 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. (jneurosci.org)
  • Stroke Traumatic brain injury Alzheimer's disease Arthritis Ebola, Cathepsin B and to a lesser extent cathepsin L have been found to be necessary for the virus to enter host cells. (wikipedia.org)
  • Additionally cathepsin D has been associated with amyloid formation in Alzheimer's plaques. (genetex.com)
  • Cathepsin zymography separates different cathepsins based on their migration through a polyacrylamide gel co-polymerized with a gelatin substrate. (wikipedia.org)
  • 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. (wikipedia.org)
  • 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). (biovision.com)
  • Cell lysates or other samples that contain cathepsins will cleave the synthetic substrate to release free AFC. (biovision.com)
  • Cathepsin F has the substrate specificity similar to that of cathepsins L and S. (neuromics.com)
  • Genomic structure, chromosomal localization, and expression of human cathepsin W". Biochem Biophys Res Commun . (wikipedia.org)
  • Transient expression of human cathepsin B in a poorly metastatic B16F1 murine melanoma variant produced a 3-5-fold increase in cathepsin B activity and a comparable increase in invasiveness. (aacrjournals.org)
  • CTSZ, which has been also known as cathepsin X and cathepsin P, exhibits carboxy-monopeptidase and carboxy-dipeptidase activities. (prospecbio.com)
  • 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. (hindawi.com)
  • 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. (bloodjournal.org)
  • Novel, Nonpeptidic Cyanamides as Potent and Reversible Inhibitors of Human Cathepsins K and L, J. Med. (patentgenius.com)
  • Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes . (wikipedia.org)
  • The catalytic sites of cathepsin D include two critical aspartic residues ( amino acid 33 and 231) located on the 14 kDa and 34kDa chains. (wikipedia.org)
  • [13] Cathepsin-D is an aspartic protease that depends critically on protonation of its active site Asp residue. (wikipedia.org)
  • 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. (bloodjournal.org)
  • Neutrophil cathepsin G increases calcium flux and inositol polyphosphate production in cultured endothelial cells. (jimmunol.org)
  • Exposure of endothelial cells (ENDO) to human neutrophil cathepsin G (CG) increases albumin flux across the endothelial monolayer. (jimmunol.org)
  • Identification of a human neutrophil angiotension II-generating protease as cathepsin G. J Clin Invest. (umassmed.edu)
  • 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. (wikipedia.org)
  • 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. (nih.gov)
  • Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. (nih.gov)
  • 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. (innovations-report.com)
  • 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. (springer.com)
  • 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. (abcam.com)
  • 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. (hindawi.com)
  • Arkona C, Wiederanders B. Expression, subcellular distribution and plasma membrane binding of cathepsin B and gelatinases in bone metastatic tissue. (springer.com)
  • Cathepsin F staining of paraffin-embedded human heart tissue sections. (neuromics.com)
  • Results: Cathepsin D demonstrates high activity in perimatrix cells adjacent to bone tissue, while it occurs in trace amounts in the matrix. (medscimonit.com)
  • Conclusions: Cathepsin D places a major role in bone tissue destruction due to cholesteatoma. (medscimonit.com)
  • 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. (ijpsonline.com)
  • Pepstatin A pretreatment did not prevent release of cathepsin D from lysosomes but did significantly inhibit subsequent naphthazarin-induced caspase activation and apoptotic morphology. (diva-portal.org)
  • Lysosomes and lysosomal cathepsins in cell death. (semanticscholar.org)
  • Cathepsin D (an aspartyl protease) appears to cleave a variety of substrates such as fibronectin and laminin. (wikipedia.org)
  • The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. (wikipedia.org)
  • Unlike some of the other cathepsins, cathepsin D has some protease activity at neutral pH. (wikipedia.org)
  • [23] Cathepsin D enzymatic activity induces hydrolytic modification of apolipoprotein B-100-containing lipoproteins, including LDL, which means it may be involved in atherosclerosis as well. (wikipedia.org)
  • oxLDL inhibits differentiation and functional activity of osteoclasts via scavenger receptor-A mediated autophagy and cathepsin K secretion. (nih.gov)
  • Cathepsin B is a papain-like cysteine protease showing both endo- and exopeptidase activity, the latter due to a unique occluding loop that restricts access to the active site cleft. (rcsb.org)
  • Finally, we tested the hypothesis that inhibiting cathepsin activity could block endometriosis lesion attachment and implantation in vivo. (nih.gov)
  • Mouse endometriotic lesions exhibit elevated cathepsin proteolytic activity. (nih.gov)
  • E-64 blocks all cathepsin proteolytic activity in murine endometriotic lesions. (nih.gov)
  • Because cathepsins have harmful effects on critical proteins such as collagen and elastin, pharmaceutical companies have been developing drugs to inhibit activity of the enzymes, but so far these compounds have had too many side effects to be useful and have failed clinical trials. (innovations-report.com)
  • The work could affect not only the development of drugs to inhibit cathepsin activity, but could also lead to a better understanding of how the enzymes work together. (innovations-report.com)
  • By increasing the amount of cathepsin S ten-fold over the amount used in the original experiment, Platt and Barry were able to completely block the activity of cathepsin K, preventing damage to the collagen sample. (innovations-report.com)
  • The selective demonstration of cathepsin B activity by means of the naphthylamide reaction. (springer.com)
  • We evaluated the activity and expression of cathepsin L, and the inhibitory effect of cysteine protease inhibitors in the umbilical cord arteries, vein and Wharton's jelly. (sigmaaldrich.com)
  • Cathepsin L activity and anti-papain inhibitory effect of cysteine protease inhibitors were quantified in extracts of separated umbilical cord tissues using fluorogenic substrates. (sigmaaldrich.com)
  • Distribution of the activity and expression of mature cathepsin L within the umbilical cord probably results from distinctions in the proenzyme activation process. (sigmaaldrich.com)
  • Cathepsin K (CatK) is a lysosomal protease with collagenolytic activity, and its secretion by osteoclasts is responsible for degrading organic bone matrix. (wiley.com)
  • Here we report that loss of cathepsin L (Cts L) is associated with a fast proliferation rate and enhanced glycolytic metabolism that depend on lactate dehydrogenase A (LDHA) activity. (mcponline.org)
  • For measuring cathepsin B activity by fluorometer or fluorescence plate reader. (promocell.com)
  • This project aims to examine the utility of the proteolytic activity signatures of caspase 1 and cathepsin S (CTSS) as readouts of particle-induced inflammation and to elucidate the role and dynamic regulation of CTSS in response to cellular stress. (bl.uk)
  • Dariusz Szajda S, Jankowski M, Zalewska B, Kożuszko B, Gabrylewski W, Skrzydlewski Z. Activity of cancer procoagulant and cathepsin D in breast cancer. (termedia.pl)
  • Immunohistochemical investigations on cathepsin D activity in structures of cholesteatoma. (medscimonit.com)
  • The aim of the present study was to evaluate the activity of cathepsin D in the structures of cholesteatoma. (medscimonit.com)
  • BACKGROUND: Serum cathepsin B activity has been considered a potential marker of tumor progression. (lu.se)
  • The aim of this study was to assess serum cathepsin activity during tumor progression and regression. (lu.se)
  • Serum cathepsin B activity was determined, tumor volumes were measured, and. (lu.se)
  • RESULTS: Of the 45 BRT-treated rats, tumor regression was observed in 31 rats, and serum cathepsin activity was analyzed in these rats. (lu.se)
  • Regional comparisons of cathepsin D activity in bovine retinal pigment epithelium. (arvojournals.org)
  • In this study, the cathepsin D activity in RPE cells from the posterior area centralis was compared to the activity in cells from the equatorial region of the same bovine eyes. (arvojournals.org)
  • Analysis of freshly isolated RPE cells from 30 eyes indicated that cells from the area centralis have significantly higher cathepsin D activity than cells from the more peripheral retina. (arvojournals.org)
  • Fluorometric kit to for fast screening of potential cathepsin B (CTSB) inhibitors. (promocell.com)
  • 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. (inria.fr)
  • Phylogenetic analyses of all the cathepsin B genes in aphids revealed that genic expansion has continuously proceeded with basal, intermediary and recent duplications. (inria.fr)
  • Cathepsin B has also been implicated in the progression of various human tumors including ovarian cancer. (wikipedia.org)
  • Mouse cathepsin L is homologous to human cathepsin V. Mouse cathepsin L has been shown to play a role in adipogenesis and glucose intolerance in mice. (wikipedia.org)
  • "Cloning and sequence analysis of cDNA for human cathepsin D" . Proceedings of the National Academy of Sciences of the United States of America . (wikipedia.org)
  • Barrett, A. J.: Human cathepsin B1. (springer.com)
  • Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease. (springer.com)
  • Distribution of cathepsin L in human umbilical cord tissues. (sigmaaldrich.com)
  • Cathepsin D has been reported to be involved in malignant tumour progression and with prognosis of various human cancers. (novusbio.com)
  • Stable antisense cathepsin B-expressing clones of the highly metastatic human melanoma A375M and prostate carcinoma PC3M cell lines produced 40-50% less cathepsin B than control cells and were proportionately less invasive. (aacrjournals.org)
  • Baici A, Müntener K, Willimann A, Zwicky R. Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death. (springer.com)
  • Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. (semanticscholar.org)
  • It was immunologically related to lysosomal cathepsin B from human liver and was similar in many, but not all, other aspects. (portlandpress.com)
  • Cathepsin S degrades elastin, and does not strongly attack collagen. (innovations-report.com)
  • We kept increasing the amount of cathepsin S until the collagen was not affected at all because all of the cathepsin K was eaten by the cathepsin S. (innovations-report.com)
  • Spinal cathepsin S and fractalkine contribute to chronic pain in the collagen-induced arthritis model," Arthritis and Rheumatism , vol. 64, no. 6, pp. 2038-2047, 2012. (hindawi.com)
  • Cathepsin B is a lysosomal cysteine proteinase whose expression and trafficking are frequently altered in cancer, and plasma membrane and secreted forms are thought to contribute to the invasive and metastatic properties of malignant tumors. (aacrjournals.org)
  • There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption. (genenames.org)
  • Cathepsin K is involved in osteoporosis, a disease in which a decrease in bone density causes an increased risk for fracture. (wikipedia.org)
  • Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. (semanticscholar.org)
  • [7] The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal compartments. (wikipedia.org)
  • Researchers for the first time have shown that members of a family of enzymes known as cathepsins - which are implicated in many disease processes - may attack one another instead of the bodily proteins they normally degrade. (innovations-report.com)
  • Using mass spectrometry analysis of cells treated with a pan cathepsin inhibitor, we observed an increased abundance of proteins involved in central carbon metabolism. (mcponline.org)
  • A cell-permeable inhibitor of calpain I, calpain II, cathepsin B, and cathepsin L. (promocell.com)
  • A cell-permeable inhibitor of calpain 1, calpain 2 which also inhibits cathepsin B, and cathepsin L. (promocell.com)
  • CTSC / Cathepsin C / JP, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that appears to be a central coordinator for activation of many serine proteinases in immune/inflammatory cells. (lsbio.com)
  • 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. (hindawi.com)
  • A direct immunohistochemical method of high specificity is presented for the demonstration of sites of cathepsin B1. (springer.com)
  • 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. (smw.ch)
  • 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. (springer.com)
  • Gingival biopsies from periodontitis patients showed a significantly higher cathepsin S expression than those from healthy gingiva. (hindawi.com)
  • Cathepsins are proteolytic enzymes with a broad spectrum of substrates. (springer.com)
  • 2017. https://www.tabers.com/tabersonline/view/Tabers-Dictionary/730869/all/cathepsins. (tabers.com)
  • Overall, we define an unexpected EPO action mode via an EPOR-Spi2A serpin-cathepsin axis in maturing erythroblasts, with lysosomal cathepsins as novel therapeutic targets. (rupress.org)
  • Cathepsin L degrades fibronectin, insulin receptor (IR), and insulin-like growth factor 1 receptor (IGF-1R). (wikipedia.org)