Studies on cathepsin L in the surimi of southern blue whiting

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.

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Biphasic modulation of human cathepsin L by a novel cyanobacterial depsipeptide

Planta Medica ◽

10.1055/s-0035-1556339 ◽

2015 ◽

Vol 81 (11) ◽

Author(s):

B Miller ◽

M Bertin ◽

V Hook ◽

WH Gerwick

Keyword(s):

Cathepsin L ◽

Human Cathepsin

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Localisation of a Novel Cathepsin L Isoform in Colorectal Cancer

Endoscopy ◽

10.1055/s-2006-956783 ◽

2006 ◽

Vol 38 (11) ◽

Author(s):

S Sullivan ◽

J O'Sullivan ◽

A Coss ◽

M Tosetto ◽

L Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cathepsin L

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Faculty Opinions recommendation of Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1118782.574865 ◽

2008 ◽

Author(s):

Amy Barrios ◽

Divya Krishnamurthy

Keyword(s):

Cathepsin L ◽

Design Synthesis

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In Silico Identification and Molecular Characterization of Extracellular Cathepsin L Proteases from Giardia duodenalis

Current Proteomics ◽

10.2174/1570164617666191016170628 ◽

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 ◽

...

Keyword(s):

In Silico ◽

Cathepsin L ◽

Three Dimensional ◽

Giardia Duodenalis ◽

Evolutionary Genetics ◽

Extracellular Proteins ◽

In Silico Identification ◽

Dimensional Models ◽

Three Dimensional Models

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.

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Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry

Scientific Reports ◽

10.1038/s41598-021-84850-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anna Goc ◽

Aleksandra Niedzwiecki ◽

Matthias Rath

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Eicosapentaenoic Acid ◽

Linolenic Acid ◽

Cathepsin L ◽

Saturated Fatty Acids ◽

Monounsaturated Fatty Acids ◽

In Vivo Experiments ◽

Lipid Compounds

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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Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00558-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Miao-Miao Zhao ◽

Wei-Li Yang ◽

Fang-Yuan Yang ◽

Li Zhang ◽

Wei-Jin Huang ◽

...

Keyword(s):

Drug Development ◽

Cathepsin L ◽

Human Cells ◽

New Drugs ◽

Disease Course ◽

Promising Target ◽

First Time

AbstractTo discover new drugs to combat COVID-19, an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed. Here, for the first time, we report the crucial role of cathepsin L (CTSL) in patients with COVID-19. The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity. Correspondingly, SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo, while CTSL overexpression, in turn, enhanced pseudovirus infection in human cells. CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry, as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo. Furthermore, amantadine, a licensed anti-influenza drug, significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo. Therefore, CTSL is a promising target for new anti-COVID-19 drug development.

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Inhibitory effect of microwave heating on cathepsin l-induced degradation of myofibrillar protein gel

Food Chemistry ◽

10.1016/j.foodchem.2021.129745 ◽

2021 ◽

Vol 357 ◽

pp. 129745

Author(s):

Qian Wang ◽

Xidong Jiao ◽

Bowen Yan ◽

Linglu Meng ◽

Hongwei Cao ◽

...

Keyword(s):

Microwave Heating ◽

Cathepsin L ◽

Inhibitory Effect ◽

Myofibrillar Protein ◽

Protein Gel

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Quinacrine-Induced Autophagy in Ovarian Cancer Triggers Cathepsin-L Mediated Lysosomal/Mitochondrial Membrane Permeabilization and Cell Death

Cancers ◽

10.3390/cancers13092004 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2004

Author(s):

Prabhu Thirusangu ◽

Christopher L. Pathoulas ◽

Upasana Ray ◽

Yinan Xiao ◽

Julie Staub ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Death ◽

Cytochrome C ◽

Cancer Cells ◽

Apoptotic Cell ◽

Cathepsin L ◽

Membrane Permeabilization ◽

Apoptotic Cell Death ◽

Ovarian Cancer Cells ◽

Autophagic Flux

We previously reported that the antimalarial compound quinacrine (QC) induces autophagy in ovarian cancer cells. In the current study, we uncovered that QC significantly upregulates cathepsin L (CTSL) but not cathepsin B and D levels, implicating the specific role of CTSL in promoting QC-induced autophagic flux and apoptotic cell death in OC cells. Using a Magic Red® cathepsin L activity assay and LysoTracker red, we discerned that QC-induced CTSL activation promotes lysosomal membrane permeability (LMP) resulting in the release of active CTSL into the cytosol to promote apoptotic cell death. We found that QC-induced LMP and CTSL activation promotes Bid cleavage, mitochondrial outer membrane permeabilization (MOMP), and mitochondrial cytochrome-c release. Genetic (shRNA) and pharmacological (Z-FY(tBU)-DMK) inhibition of CTSL markedly reduces QC-induced autophagy, LMP, MOMP, apoptosis, and cell death; whereas induced overexpression of CTSL in ovarian cancer cell lines has an opposite effect. Using recombinant CTSL, we identified p62/SQSTM1 as a novel substrate of CTSL, suggesting that CTSL promotes QC-induced autophagic flux. CTSL activation is specific to QC-induced autophagy since no CTSL activation is seen in ATG5 knockout cells or with the anti-malarial autophagy-inhibiting drug chloroquine. Importantly, we showed that upregulation of CTSL in QC-treated HeyA8MDR xenografts corresponds with attenuation of p62, upregulation of LC3BII, cytochrome-c, tBid, cleaved PARP, and caspase3. Taken together, the data suggest that QC-induced autophagy and CTSL upregulation promote a positive feedback loop leading to excessive autophagic flux, LMP, and MOMP to promote QC-induced cell death in ovarian cancer cells.

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Effectiveness of Gutting Blue Whiting (Micromesistius poutassou, Risso, 1827), in Spanish Supermarkets as an Anisakidosis Safety Measure

Foods ◽

10.3390/foods10040862 ◽

2021 ◽

Vol 10 (4) ◽

pp. 862

Author(s):

Ana Elena Ahuir-Baraja ◽

Lola Llobat ◽

Maria Magdalena Garijo

Keyword(s):

Food Safety ◽

Direct Relationship ◽

Infected Fish ◽

Total Removal ◽

Safety Measures ◽

Blue Whiting ◽

Total Prevalence ◽

The World ◽

Human Infections ◽

Additional Safety

Anisakidosis is a parasitic zoonotic disease which can cause gastroallergic reactions in humans. In 2010, the European Food Safety Agency estimated that approximately 20,000 cases of anisakiasis had been reported across the world, with Spain having the highest number of infections in Europe. The blue whiting (Micromesistius poutassou, Risso, 1827) is one of the most widely fished species worldwide and represents around 25% of the white fish eaten in Spain. The Spanish Food Safety Authority requires obligatory evisceration of certain fish species before commercialization, but not for blue whiting. Nevertheless, some supermarkets carry this out themselves to prevent human infections and negative customer reactions deriving from the presence of ascaridoid larvae. To assess the effectiveness of eviscerations at supermarkets, a total of 320 blue whiting specimens were examined. The risk of larval migration from the visceral cavity to the musculature in gutted and ungutted fish was also assessed. Our results showed a total prevalence (25%) of ascaridoids in fish gutted at the supermarket, and a direct relationship was found between the presence of larvae in the muscle and time until evisceration. In ungutted fish, the standard length and weight were higher for infected than for non-infected fish. Also, massive infections had a higher prevalence in these larger specimens, in which the viability of larvae was also high. Larval viability was not found to be affected by a 24-h refrigeration period. Anisakis was the most prevalent genus identified in the fish examined. The results indicate that gutting at the supermarket is not an effective method for the total removal of ascaridoid larvae and that additional safety measures are advisable.

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