Surface activation of pro-cathepsin L

1992 ◽  
Vol 189 (3) ◽  
pp. 1659-1666 ◽  
Author(s):  
Robert W. Mason ◽  
Steven D. Massey
2005 ◽  
Vol 41 ◽  
pp. 173-186 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.


Planta Medica ◽  
2015 ◽  
Vol 81 (11) ◽  
Author(s):  
B Miller ◽  
M Bertin ◽  
V Hook ◽  
WH Gerwick
Keyword(s):  

1995 ◽  
Vol 74 (03) ◽  
pp. 991-992 ◽  
Author(s):  
D A Tsakiris ◽  
W E Haefeli ◽  
L Linder ◽  
B Steiner ◽  
G A Marbet

Endoscopy ◽  
2006 ◽  
Vol 38 (11) ◽  
Author(s):  
S Sullivan ◽  
J O'Sullivan ◽  
A Coss ◽  
M Tosetto ◽  
L Wang ◽  
...  

2019 ◽  
Author(s):  
Sina Chaeichian ◽  
Kaspar Schaerer ◽  
Ruairi O’Kane ◽  
Michael Halbasch

2010 ◽  
Vol 34 (3) ◽  
pp. 336-341
Author(s):  
Ya-qin HU ◽  
Yan-jia YAO ◽  
Jian-chu CHEN
Keyword(s):  

2020 ◽  
Vol 17 (4) ◽  
pp. 342-351
Author(s):  
Sergio A. Durán-Pérez ◽  
José G. Rendón-Maldonado ◽  
Lucio de Jesús Hernandez-Diaz ◽  
Annete I. Apodaca-Medina ◽  
Maribel Jiménez-Edeza ◽  
...  

Background: The protozoan Giardia duodenalis, which causes giardiasis, is an intestinal parasite that commonly affects humans, mainly pre-school children. Although there are asymptomatic cases, the main clinical features are chronic and acute diarrhea, nausea, abdominal pain, and malabsorption syndrome. Little is currently known about the virulence of the parasite, but some cases of chronic gastrointestinal alterations post-infection have been reported even when the infection was asymptomatic, suggesting that the cathepsin L proteases of the parasite may be involved in the damage at the level of the gastrointestinal mucosa. Objective: The aim of this study was the in silico identification and characterization of extracellular cathepsin L proteases in the proteome of G. duodenalis. Methods: The NP_001903 sequence of cathepsin L protease from Homo sapienswas searched against the Giardia duodenalisproteome. The subcellular localization of Giardia duodenaliscathepsin L proteases was performed in the DeepLoc-1.0 server. The construction of a phylogenetic tree of the extracellular proteins was carried out using the Molecular Evolutionary Genetics Analysis software (MEGA X). The Robetta server was used for the construction of the three-dimensional models. The search for possible inhibitors of the extracellular cathepsin L proteases of Giardia duodenaliswas performed by entering the three-dimensional structures in the FINDSITEcomb drug discovery tool. Results: Based on the amino acid sequence of cathepsin L from Homo sapiens, 8 protein sequences were identified that have in their modular structure the Pept_C1A domain characteristic of cathepsins and two of these proteins (XP_001704423 and XP_001704424) are located extracellularly. Threedimensional models were designed for both extracellular proteins and several inhibitory ligands with a score greater than 0.9 were identified. In vitrostudies are required to corroborate if these two extracellular proteins play a role in the virulence of Giardia duodenalisand to discover ligands that may be useful as therapeutic targets that interfere in the mechanism of pathogenesis generated by the parasite. Conclusion: In silicoanalysis identified two proteins in the Giardia duodenalisprotein repertoire whose characteristics allowed them to be classified as cathepsin L proteases, which may be secreted into the extracellular medium to act as virulence factors. Three-dimensional models of both proteins allowed the identification of inhibitory ligands with a high score. The results suggest that administration of those compounds might be used to block the endopeptidase activity of the extracellular cathepsin L proteases, interfering with the mechanisms of pathogenesis of the protozoan parasite Giardia duodenalis.


Coatings ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Ruslan Rushanovich Safin ◽  
Aigul Ravilevna Shaikhutdinova ◽  
Ruslan Khasanshin ◽  
Shamil Mukhametzyanov ◽  
Albina Safina

This work is devoted to the study of the effect of ultraviolet rays for the surface activation of pine wood thermally modified at temperatures of 180−240 °C in order to increase the surface roughness, enhance the wettability of thermal wood and the adhesive strength of the glue in the production of wood block furniture panels. Studies were carried out to measure the contact angle of wettability of thermally modified wood samples of pine, as a result of which it was determined that the ultraviolet treatment process contributes to an increase in the adhesion properties of the surface layer of thermally modified wood by more than 13% due to the reactivity of ultraviolet rays to oxidize and degrade ligno-containing wood products. At the same time, the most active process of surface activation takes place during 60 min of ultraviolet irradiation of wood with a total irradiation of at least 125 W/cm2. It was revealed that the combined effect of two-stage wood processing, including preliminary volumetric thermal modification followed by surface ultraviolet treatment, causes an increase in the moisture resistance of glued wood products by 24%. So, if the strength of the glue seam when gluing natural wood samples after boiling decreased by 46%, then the samples that underwent two-stage processing showed a decrease only by 22%. In connection with the results obtained, an improved technology for the production of furniture boards for the manufacture of moisture-resistant wood products is proposed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Goc ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath

AbstractThe strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.


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