Disease relevance of Ctsb

• Ctsb inhibition may be therapeutic in liver diseases [1].
• Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection [2].
• Cellular distribution of ctsb-green fluorescent protein (ctsb-GFP) in a rat hepatoma cell line was imaged by confocal microscopy. ctsb-GFP fluorescence was punctate under basal conditions but became diffuse after treatment with TNF-alpha/actinomycin D [3].
• Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis [4].
• Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis [1].

Psychiatry related information on Ctsb

• Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer's disease [5].

High impact information on Ctsb

• The activity of the lysosomal proteinase cathepsin B is significantly elevated in a variant of the B16 melanoma with high metastatic potential [6].
• The cathepsin B activity is localized to the lysosomes of the tumor cells [6].
• Since homogenates of leupeptin-treated muscles had decreased cathepsin B activity, this lysosomal protease may play a role in protein turnover in normal and diseased muscles [7].
• Mutants of cathepsins B or S impaired tumor formation and angiogenesis, while cathepsin B or L knockouts retarded cell proliferation and tumor growth [8].
• The cysteine protease cathepsin B (CatB) is associated with amyloid plaques in AD brains and has been suspected to increase Abeta production [5].

Chemical compound and disease context of Ctsb

• We show here that mouse mammary tumor virus-polyoma middle T antigen (PyMT) transgenic mice deficient for the cysteine protease cathepsin B (CTSB) exhibited a significantly delayed onset and reduced growth rate of mammary cancers compared with wild-type PyMT mice [9].
• At the same time, a marked increase in cathepsin B and cathepsin L activity in LS lymphosarcoma was found, indicating the involvement of apoptosis in the mechanism of antitumor action of cyclophosphamide [10].
• In contrast, Moloney murine sarcoma virus-transformed BALB/3T3 fibroblasts (MMSV) secreted greatly increased amounts of latent cathepsin B (17-fold) and latent cathepsin L (27-fold), and moderately increased amounts of active beta-glucuronidase (2-fold) in a manner which was not further increased by monensin [11].
• In vitro studies used quiescent murine splenic or pulmonary macrophages (10(5)/mL) which were exposed to media alone (control), trypsin, chymotrypsin, cathepsin-B, 20% ascites (vol/vol), 50% ascites, or endotoxin (lipopolysaccharide, 10 micrograms/mL, positive control) for 4 hours [12].
• Leupeptin, a cathepsin B inhibitor, when administered as a single agent was devoid of antimetastatic activity but some therapeutic activity was noted in mice with Lewis lung carcinoma when the agent was administered in combination with adriamycin [13].

Biological context of Ctsb

• Although a lysosomal, cathepsin B-dependent (Ctsb-dependent) pathway of apoptosis has been described, the contribution of this pathway to tissue damage remains unclear [1].
• Localization of the mRNA species for cystatin C and cathepsin B, as well as, localization of protein species for cystatin C, cathepsins B and L were performed to evaluate the tissue distribution of these species [14].
• The phenotype is reproduced by antisense cathepsin B expression in parental C2C12 myoblasts [15].
• With the regression of the decidua beginning on day 9.5, a coordinated upregulation of both cathepsin B and cystatin C was observed implying a role for controlled cathepsin expression during apoptosis [16].
• Furthermore, lung colonization studies of PyMT cells with different CTSB genotypes injected into congenic wild-type mice and in vitro Matrigel invasion assays confirmed a specific role for tumor-derived CTSB in invasion and metastasis [9].

Anatomical context of Ctsb

• Our aim was to ascertain if Ctsb inactivation attenuates liver injury, inflammation, and fibrogenesis after bile duct ligation (BDL) [1].
• Both genetic and pharmacologic inhibition of Ctsb in the BDL mouse reduced (a). hepatic inflammation, as assessed by transcripts for CXC chemokines and neutrophil infiltration, and (b). fibrogenesis, as assessed by transcripts for stellate cell activation and sirius red staining for hepatic collagen deposition [1].
• In contrast, hepatocyte apoptosis and liver damage were reduced in Ctsb(-/-) and cathepsin B inhibitor-treated mice fed the MCD diet following CI/WR injury [17].
• Impaired proteolysis resulted in the persistence of thyroglobulin in the thyroids of mice with deficiencies in cathepsin B or L [18].
• Native-gel electrophoresis and gel filtration chromatography demonstrate that, in both cell lines, the double-chain form of cathepsin B is sequestered in a large molecular weight complex that renders this form of the enzyme inactive [2].

Associations of Ctsb with chemical compounds

• Cathepsin B is the major cysteine protease in the RPE and choroid [14].
• Moreover, CA-074, a specific cathepsin B inhibitor, also abolished the neurotoxic effects caused by Abeta42-activated BV2 cells [19].
• Recent studies suggested that N-acetylcysteine enhances the extracellular degradation of PDGF-beta receptor by cathepsin B, thus suggesting that the absence of PDGF-beta receptors in quiescent cells is due to an active process of elimination and not to a lack of expression [20].
• It is shown that MGX (methylglyoxal), GO (glyoxal) and glycolaldehyde, but not hydroxyacetone and glucose, inhibit catB (cathepsin B), catL (cathepsin L) and catS (cathepsin S) activity in macrophage cell lysates, in a concentration-dependent manner [21].
• Although inhibitors of cathepsin B (leupeptin, antipain, N alpha-p-tosyl-L-lysine chloromethyl ketone, and chymostatin) were able to inhibit the release of monoiodotyrosine from treated cells in a time- and concentration-dependent manner, they had little effect on the processing step that apparently inactivates 125I-EGF [22].
• Cathepsin B and MMP-2 activities were decreased in Pseudomonas-infected NE knockout mice compared with wild-type littermates [23].

Physical interactions of Ctsb

• Cathepsin B expression is under transcriptional control in murine melanomas and the major promoter contains potential binding sites for the Sp1 transcription factor [24].

Enzymatic interactions of Ctsb

• Parenteral administration of sericystatin A, an intracellular leukocyte inhibitor of the proinsulin-splitting enzyme cathepsin B, prolongs the mean survival time of mice with insulin-dependent myeloid leukemia [25].

Regulatory relationships of Ctsb

• Cathepsin B has previously been shown to proteolytically activate the proinflammatory caspase-11 in vitro [26].
• Cathepsin B-inhibitor promotes the development of Th1 type protective T cells in mice infected with Leishmania major [27].
• The cathepsin B inhibitor z-FA.fmk inhibits cytokine production in macrophages stimulated by lipopolysaccharide [26].
• Sp1 regulates cathepsin B transcription and invasiveness in murine B16 melanoma cells [24].
• Only known inhibitors of macrophage elastase blocked the activity of elastase-rich cell-conditioned medium whereas inhibitors of cathepsin B also suppressed intact cell activity [28].

Other interactions of Ctsb

• Recent evidence suggests that cathepsin B (cat B) contributes to TNF-alpha-induced apoptosis in vitro [29].
• In addition, the aspecific inhibition of cathepsin B by so-called specific caspase inhibitors implicates that results obtained with these inhibitors should be interpreted with care [30].
• A partial reduction of cathepsin B protein raised the possibility that the siRNA effect on the matrix protease activity could have been attributable to cathepsin L or B [31].
• Cathepsin B-mediated activation of the proinflammatory caspase-11 [30].
• Mixed lysates of L cells and LX cells lack activity of both cathepsin B and cathepsin L, suggesting the presence of an inhibitor of cathepsin function in LX cells [2].

Analytical, diagnostic and therapeutic context of Ctsb

• A cathepsin B-green fluorescent protein (GFP) fusion protein expressed in L cells and purified by immunoprecipitation retains cathepsin B activity, whereas cathepsin B-GFP expressed in LX cells does not [2].
• Northern blots showed that trophoblast expressed cathepsin B throughout the invasive period (days 5.5-10.5) [16].
• The results show that cathepsin B release is an early event following occlusion of cerebral arteries, which eventually triggers the activation of proinflammatory caspases in the absence of reperfusion [32].
• Immunohistochemistry revealed the colocalization of cathepsin B with each caspase in cells of the infarct core [32].
• Immunofluorescence analysis of the lysosomal enzymes cathepsin B and D showed a punctated intracellular pattern consistent with lysosomal localization in wild-type mice fed a standard diet after CI/WR injury [17].

References