Search results for "Cathepsin L"
showing 10 items of 42 documents
Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implicati…
1997
The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as comp…
Expression of cysteine proteinases cathepsins B and K and of cysteine proteinase inhibitor cystatin C in giant cell tumor of tendon sheath.
2001
The expression of cysteine proteinases cathepsins B and K and of the endogenous inhibitor of cysteine proteinases, cystatin C, was investigated in tissue specimens of patients with giant cell tumor of tendon sheath (GCTTS). Expression of both enzymes was examined by immunohistochemistry in tissue specimens of 14 patients with GCTTS. Applying double-labeling techniques, the coexpression of cathepsin B and its major endogenous inhibitor cystatin C was additionally studied. Cells expressing the respective proteins were further characterized with the macrophage markers HAM56 and anti-CD68 (clone PG-M1). Cathepsin B could be detected in numerous HAM56-positive mononuclear cells (MC), but only in…
Lysosomal aspartic and cysteine proteinases serum levels in patients with pancreatic cancer or pancreatitis
1997
Lysosomal cathepsins D (CD), B (CB), and L (CL) serum levels were determined by immunoassays in patients with chronic (CHP) or acute (AP) pancreatitis and in patients with ductal pancreatic carcinoma (DPC) and correlated with some biological and clinical parameters of this tumor. CB serum concentrations significantly higher than those measured in healthy subjects (NS) were observed in CHP, AP, and DPC patients (p < 0.01). However, no significant difference was noted among these groups. Increased CL serum levels were evident only in cancer patients compared to NS, AP, or CHP groups (p < 0.05), while no difference was observed among these groups. Elevated CD serum values were observed i…
The Extracellular Vesicles of the Helminth Pathogen, Fasciola hepatica : Biogenesis Pathways and Cargo Molecules Involved in Parasite Pathogenesis
2015
Extracellular vesicles (EVs) released by parasites have important roles in establishing and maintaining infection. Analysis of the soluble and vesicular secretions of adult Fasciola hepatica has established a definitive characterisation of the total secretome of this zoonotic parasite. Fasciola secretes at least two sub-populations of EVs that differ according to size, cargo molecules and site of release from the parasite. The larger EVs are released from the specialised cells that line the parasite gastrodermus and contain the zymogen of the 37 kDa cathepsin L peptidase that performs a digestive function. The smaller exosome-like vesicle population originate from multivesicular bodies with…
Cathepsin L in metastatic bone disease: therapeutic implications
2010
AbstractCathepsin L is a lysosomal cysteine proteinase primarily devoted to the metabolic turnover of intracellular proteins. However, accumulating evidence suggests that this endopeptidase might also be implicated in the regulation of other important biological functions, including bone resorption in normal and pathological conditions. These findings support the concept that cathepsin L, in concert with other proteolytic enzymes involved in bone remodeling processes, could contribute to facilitate bone metastasis formation. In support of this hypothesis, recent studies indicate that cathepsin L can foster this process by triggering multiple mechanisms which, in part, differ from those of t…
Partial restoration of pre-transformation levels of lysyl oxidase and transin mRNAs in phenotypic ras revertants.
1995
Neoplastic transformation mediated by ras oncogenes is associated with deregulated expression of genes encoding, for example, various proteases, lysyl oxidase, and smooth-muscle α-actin. To define the role of these genes in the initiation or maintenance of the ras-transformed state, we compared their steady-state mRNA levels in two different sets of preneoplastic fibroblast lines, ras-transformed clones, and phenotypic revertants derived from them. Compared with the preneoplastic fibroblasts, the ras-transformed derivatives exhibited elevated levels of cathepsin L (major excreted protein), transin (stromelysin I, matrix metalloproteinase–3), and collagenase I (matrix metalloproteinase–1) mR…
Natural products as inhibitors of recombinant cathepsin L of Leishmania mexicana.
2015
Cysteine proteinases (cathepsins) from Leishmania spp. are promising molecular targets against leishmaniasis. Leishmania mexicana cathepsin L is essential in the parasite life cycle and a pivotal in virulence factor in mammals. Natural products that have been shown to display antileishmanial activity were screened as part of our ongoing efforts to design inhibitors against the L. mexicana cathepsin L-like rCPB2.8. Among them, agathisflavone (1), tetrahydrorobustaflavone (2), 3-oxo-urs-12-en-28-oic acid (3), and quercetin (4) showed significant inhibitory activity on rCPB2.8 with IC50 values ranging from 0.43 to 18.03 µM. The mechanisms of inhibition for compounds 1–3, which showed Ki values…
Silicateins, the major biosilica forming enzymes present in demosponges: protein analysis and phylogenetic relationship.
2007
Silicateins are enzymes, which are restricted to sponges (phylum Porifera), that mediate the catalytic formation of biosilica from monomeric silicon compounds. The silicatein protein is compartmented in the sponges in the axial filaments which reside in the axial canals of the siliceous spicules. In the present study silicatein has been isolated from the freshwater sponge Lubomirskia baicalensis where it occurs in isoforms with sizes of 23 kDa, 24 kDa and 26 kDa. Since the larger protein is glycosylated we posit that it is a processed form of one of the smaller size forms. The silicatein isoforms are post-translationally modified by phosphorylation; at least four isoforms exist with pI's of…
Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection
2014
Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb) and L (Ctsl) play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrop…
Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings…
2016
The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluo…