Detection of cathepsin L-like proteinase and cathepsin D in gingival fluid

1986 ◽  
Vol 21 (5) ◽  
pp. 504-509 ◽  
Author(s):  
Tamara Lah ◽  
Uroser Skallric ◽  
Joza Babnik ◽  
Vito Turk
Keyword(s):  
Cathepsin D ◽  
Cathepsin L ◽  
Gingival Fluid

Long-Term Follow-Up Confirms Prognostic Impact of Pai-1 and Cathepsin D and L in Primary Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 79-83 ◽  
Author(s):  
N. Harbeck ◽  
U. Alt ◽  
U. Berger ◽  
R. Kates ◽  
A. Krüger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Cathepsin D ◽  
Cathepsin L ◽  
Lymph Node Status ◽  
Prognostic Impact ◽  
Long Term Follow Up ◽  
Pai 1

After long-term follow-up, the prognostic impact of the following proteolytic factors associated with tumor invasion and metastasis was evaluated in 276 primary breast cancer patients: uPA (urokinase-type plasminogen activator), PAI-1 (uPA inhibitor type 1), and cathepsins B, D and L. The median follow-up of patients still alive at the time of analysis was 109 months. To date 119 patients (43%) have relapsed and 117 (42%) have died. Antigen levels of uPA and PAI-1 were determined by ELISA in detergent extracts; cathepsin B, D, and L content was determined in cytosol fractions of the primary tumor: cathepsin D by ELSA and cathepsin B and L by ELISA. In multivariate analysis (Cox model) for disease-free survival (DFS), lymph node status (p<0.001; RR=3.8), cathepsin L (p<0.001; RR=2.6) and PAI-1 (p=0.027; RR=1.7) were significant factors in all patients. In addition to these factors, grading was significant for overall survival (OS). In another multivariate approach, CART (Classification And Regression Trees) analysis, lymph node status (p<0.001) turned out to be the strongest discriminator for patients at high risk of relapse. In the node-negative patient subset, PAI-1 was the strongest risk group discriminator (p<0.001): in this subset, patients with low levels of both PAI-1 and cathepsin D had a very low relapse rate of only 3.2% compared to 39% in the remaining node-negative patients. In node-positive patients cathepsin L gave the best risk group assessment (p=0.001). In conclusion, tumor-associated PAI-1 and cathepsins D and L provide significant, statistically independent prognostic information for DFS and OS in primary breast cancer, even after a median follow-up period of almost 10 years.

scholarly journals Proteases as Therapeutic Targets Against the Parasitic Cnidarian Ceratonova shasta: Characterization of Molecules Key to Parasite Virulence In Salmonid Hosts

2022 ◽  
Vol 11 ◽  
Author(s):  
Gema Alama-Bermejo ◽  
Pavla Bartošová-Sojková ◽  
Stephen D. Atkinson ◽  
Astrid S. Holzer ◽  
Jerri L. Bartholomew
Keyword(s):  
Pacific Northwest ◽  
Cathepsin D ◽  
Cell Metabolism ◽  
Cathepsin L ◽  
Cysteine Proteases ◽  
Aminopeptidase N ◽  
Cysteine Protease Inhibitor ◽  
Parasite Development ◽  
Future Research ◽  
3D Protein Structure

Proteases and their inhibitors play critical roles in host-parasite interactions and in the outcomes of infections. Ceratonova shasta is a myxozoan pathogen that causes enteronecrosis in economically important salmonids from the Pacific Northwest of North America. This cnidarian parasite has host-specific genotypes with varying virulence, making it a powerful system to decipher virulence mechanisms in myxozoans. Using C. shasta genome and transcriptome, we identified four proteases of different catalytic types: cathepsin D (aspartic), cathepsin L and Z-like (cysteine) and aminopeptidase-N (metallo); and a stefin (cysteine protease inhibitor), which implied involvement in virulence and hence represent target molecules for the development of therapeutic strategies. We characterized, annotated and modelled their 3D protein structure using bioinformatics and computational tools. We quantified their expression in C. shasta genotype 0 (low virulence, no mortality) and IIR (high virulence and mortality) in rainbow trout Oncorhynchus mykiss, to demonstrate that there are major differences between the genotypes during infection and parasite development. High proliferation of genotype IIR was associated with high expression of the cathepsin D and the stefin, likely correlated with high nutrient demands and to regulate cell metabolism, with upregulation preceding massive proliferation and systemic dispersion. In contrast, upregulation of the cathepsin L and Z-like cysteine proteases may have roles in host immune evasion in genotype 0 infections, which are associated with low proliferation, low inflammation and non-destructive development. In contrast to the other proteases, C. shasta aminopeptidase-N appears to have a prominent role in nematocyst formation in both genotypes, but only during sporogenesis. Homology searches of C. shasta proteases against other myxozoan transcriptomes revealed a high abundance of cathepsin L and aminopeptidase homologs suggesting common gene requirements across species. Our study identified molecules of potential therapeutic significance for aquaculture and serves as a baseline for future research aimed at functional characterisation of these targets.

Novel N-(2-Methoxydibenzofuran-3-yl)-2-aryloxyacetamide Derivatives: Synthesis and Biological Investigation

2020 ◽  
Vol 17 ◽  
Author(s):  
Leyla Yurttaş ◽  
Betül Kaya Çavuşoğlu ◽  
Halide Edip Temel ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Lines ◽  
Cathepsin D ◽  
Cathepsin L ◽  
Biological Applications ◽  
Biological Investigation ◽  
Natural Sources ◽  
Ic50 Values ◽  
Wide Scale ◽  
Nih 3T3 ◽  
A549 Lung

Background: Dibenzofuran ring is a typical heterocyle which is found in many natural sources and its derivatives exhibit a wide scale of biological applications similar to its analog ring systems; furan and benzofuran. Methods: Novel N-(2-methoxydibenzofuran-3-yl)-2-aryloxyacetamide derivatives (2a-l) were synthesized and evaluated for their cytotoxic activity against A549 lung cancer and NIH/3T3 mouse embryofibroblast cell lines. The inhibition percentages of cathepsin D, L, acetylcholinesterase (AChE) and butrylcholinesterase (BuChE) enzymes provoked by the compounds were also determined. Results and Discussion: Most of the compounds exhibited significant cytotoxicity whose IC50 values were identified lower than the tested lowest concentration (<3.90 µg/mL). Compounds 2i against cathepsin D and compound 2k against cathepsin L displayed the highest inhibitory activity. Regrettably, the compounds demonstrated very weak AChE and BuChE inhibition. Conclusion: Compounds 2b, 2c, 2e, 2i and 2k exhibited the highest antiproliferative activity against A549 cell lines with selective profile. However, they did not display satisfying results on tested enzymes.

Impaired turnover of autophagolysosomes in cathepsin L deficiency

2010 ◽  
Vol 391 (8) ◽  
Author(s):  
Julia Dennemärker ◽  
Tobias Lohmüller ◽  
Sebastian Müller ◽  
Stephanie Vargas Aguilar ◽  
Desmond J. Tobin ◽  
...  
Keyword(s):  
Hair Loss ◽  
Cathepsin D ◽  
Cathepsin L ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Cellular Compartment ◽  
Dilative Cardiomyopathy ◽  
Primary Mouse ◽  
Significant Impairment ◽  
Acidic Vesicles

Abstract Some of the phenotypes of mice deficient for the lysosomal cysteine endopeptidase cathepsin L (Ctsl) are characterized by large dysmorphic vesicles in the cytoplasm. Specifically, the heart (dilative cardiomyopathy), the thyroid (impaired thyroglobulin processing) and keratinocytes (periodic hair loss and epidermal hyperproliferation) are affected. We hypothesized that the formation of aberrant vesicles is owing to defects in macroautophagy. Therefore, primary mouse embryonic fibroblasts (MEF), which were derived from Ctsl -/- animals crossed with mice transgenic for the autophagy marker GFP-LC3, were investigated. Ctsl -/- MEF show increased number and size of vesicular structures belonging to the ‘acidic’ cellular compartment and are also characterized by GFP-LC3. Induction of autophagy by nutrient starvation or rapamycin treatment showed no significant impairment of the initiation of autophagy, the formation of autophagosomes or autophagosome-lysosome fusion in Ctsl -/- MEF, but co-localization of GFP-LC3 and Lamp1 revealed unusually large autophagolysosomes filled with Lamp1. Furthermore, the soluble lysosomal enzyme cathepsin D was elevated in Ctsl -/- MEF. Thus, degradation of autophagolysosomal content is impaired in the absence of Ctsl. This could slow the turnover of autophagolysosomes and result in accumulation of the dysmorphic and ‘acidic’ vesicles that were previously described in the context of the pathological phenotypes of Ctsl -/- mice.

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