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 ...

Enzymatic activity of cathepsin B, cathepsin B and L, plasmin, trypsin and collagenase in hepatocellular carcinoma]. Pol Arch Med Wewn. 2002 Jul; 108(1):653-62 ...

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.

HEADER HYDROLASE/HYDROLASE INHIBITOR 11-MAY-10 3AI8 TITLE CATHEPSIN B IN COMPLEX WITH THE NITROXOLINE COMPND MOL_ID: 1; COMPND 2 MOLECULE: CATHEPSIN B; COMPND 3 CHAIN: B, A; COMPND 4 SYNONYM: CATHEPSIN B1, APP SECRETASE, APPS, CATHEPSIN B LIGHT CHAIN, COMPND 5 CATHEPSIN B HEAVY CHAIN; COMPND 6 EC: 3.4.22.1; COMPND 7 ENGINEERED: YES SOURCE MOL_ID: 1; SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS; SOURCE 3 ORGANISM_COMMON: HUMAN; SOURCE 4 ORGANISM_TAXID: 9606; SOURCE 5 GENE: CTSB; SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI; SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562; SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21DE3; SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID; SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET3A KEYWDS CATHEPSIN B, REVERSIBLE INHIBITOR, NITROXOLINE, 8-HYDROXY-5- KEYWDS 2 NITROQUINOLINE, HYDROLASE-HYDROLASE INHIBITOR COMPLEX EXPDTA X-RAY DIFFRACTION AUTHOR M.RENKO,B.MIRKOVIC,S.GOBEC,J.KOS,D.TURK REVDAT 3 29-JAN-14 3AI8 1 JRNL VERSN REVDAT 2 08-JUN-11 3AI8 1 JRNL REVDAT 1 18-MAY-11 3AI8 0 JRNL AUTH ...

OBJECTIVE To measure the cardiovascular threat of diabetic subject matter with chronic kidney disease (CKD) predicated on different approximated glomerular filtration rate (eGFR) equations also to evaluate which definition of CKD best improves cardiovascular risk prediction from the Framingham Cardiovascular Risk Score (Framingham-CV-RS). Outcomes During 5 many years of follow-up, 95 people had a major cardiovascular event. Crude HRs had been increased for many CKD definitions. Nevertheless, after CI-1040 modifying for founded cardiovascular risk elements, HRs for both creatinine-based CKD meanings had been attenuated to stage estimates of just one 1.03, whereas the HRs for the cystatin CCbased CKD description continued to be significantly increased (HR 1.75 [95% CI 1.07C2.87]). Expansion of the research model by the various CKD definitions led to a rise in the statistic only once SCKL adding CKD-CysC (from 0.638 to 0.644) plus a net CI-1040 reclassification improvement of 8.9%. CONCLUSIONS Just ...

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 ...

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The conserved oligomeric complex (COG) is a multi-subunit vesicle tethering complex that functions in retrograde trafficking at the Golgi. We have previously demonstrated that the formation of enlarged endo-lysosomal structures (EELSs) is one of the major glycosylation-independent phenotypes of cells depleted for individual COG complex subunits. Here, we characterize the EELSs in HEK293T cells using microscopy and biochemical approaches. Our analysis revealed that the EELSs are highly acidic and that vATPase-dependent acidification is essential for the maintenance of this enlarged compartment. The EELSs are accessible to both trans-Golgi enzymes and endocytic cargo. Moreover, the EELSs specifically accumulate endolysosomal proteins Lamp2, CD63, Rab7, Rab9, Rab39, Vamp7, and STX8 on their surface. The EELSs are distinct from lysosomes and do not accumulate active Cathepsin B. Retention using selective hooks (RUSH) experiments revealed that biosynthetic cargo mCherry-Lampl reaches the EELSs much ...

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 ...

Gentaur molecular products has all kinds of products like :search , BPS Bioscience \ Cathepsin B \ 80001 for more molecular products just contact us

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 ...