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Cathepsin G

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https://www.readbyqxmd.com/read/29779708/imaging-mass-spectrometry-reveals-direct-albumin-fragmentation-within-the-diabetic-kidney
#1
Kerri J Grove, Nichole M Lareau, Paul A Voziyan, Fenghua Zeng, Raymond C Harris, Billy G Hudson, Richard M Caprioli
Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology...
May 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29777136/functional-proteomic-profiling-of-secreted-serine-proteases-in-health-and-inflammatory-bowel-disease
#2
Alexandre Denadai-Souza, Chrystelle Bonnart, Núria Solà Tapias, Marlène Marcellin, Brendan Gilmore, Laurent Alric, Delphine Bonnet, Odile Burlet-Schiltz, Morley D Hollenberg, Nathalie Vergnolle, Céline Deraison
While proteases are essential in gastrointestinal physiology, accumulating evidence indicates that dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease (IBD). Nonetheless, the identity of overactive proteases released by human colonic mucosa remains largely unknown. Studies of protease abundance have primarily investigated expression profiles, not taking into account their enzymatic activity. Herein we have used serine protease-targeted activity-based probes (ABPs) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy controls and IBD patients...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29746165/a-lysosome-plasma-membrane-sphingolipid-axis-linking-lysosomal-storage-to-cell-growth-arrest
#3
Maura Samarani, Nicoletta Loberto, Giulia Soldà, Letizia Straniero, Rosanna Asselta, Stefano Duga, Giulia Lunghi, Fabio A Zucca, Laura Mauri, Maria Grazia Ciampa, Domitilla Schiumarini, Rosaria Bassi, Paola Giussani, Elena Chiricozzi, Alessandro Prinetti, Massimo Aureli, Sandro Sonnino
Lysosomal accumulation of undegraded materials is a common feature of lysosomal storage diseases, neurodegenerative disorders, and the aging process. To better understand the role of lysosomal storage in the onset of cell damage, we used human fibroblasts loaded with sucrose as a model of lysosomal accumulation. Sucrose-loaded fibroblasts displayed increased lysosomal biogenesis followed by arrested cell proliferation. Notably, we found that reduced lysosomal catabolism and autophagy impairment led to an increase in sphingolipids ( i...
May 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29722459/selective-on-off-nitroxides-as-radical-probes-to-investigate-non-radical-enzymatic-activity-by-electron-paramagnetic-resonance
#4
Indranil Duttagupta, Natacha Jugniot, Gérard Audran, Jean-Michel Franconi, Sylvain R A Marque, Philippe Massot, Philippe Mellet, Elodie Parzy, Eric Thiaudière, Nicolas Vanthuyne
A nitroxide carrying a peptide specific to the binding pocket of the serine proteases chymotrypsin and cathepsin G is prepared. This peptide is attached as an enol ester to the nitroxide. Upon enzymatic hydrolysis of the peptide, the enol ester moiety is transformed into a ketone moiety. This transformation affords a difference of 5 G in phosphorus hyperfine coupling constant between the electronic paramagnetic resonance (EPR) signals of each nitroxide. This property is used to monitor the enzymatic activity of chymotrypsin and cathepsin G by EPR...
May 3, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29703634/human-mast-cell-neutral-proteases-generate-modified-ldl-particles-with-increased-proteoglycan-binding
#5
Katariina Maaninka, Su Duy Nguyen, Mikko I Mäyränpää, Riia Plihtari, Kristiina Rajamäki, Perttu J Lindsberg, Petri T Kovanen, Katariina Öörni
BACKGROUND AND AIMS: Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. METHODS: Mature human MCs were differentiated from human peripheral blood-derived CD34+ progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium...
April 13, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29703471/the-intersection-of-protein-disulfide-isomerase-and-cancer-associated-thrombosis
#6
Jack D Stopa, Jeffrey I Zwicker
The mechanisms underlying the hypercoagulability of cancer are complex and include the upregulation coagulation factors or procoagulant proteins, shedding of microparticles, and direct activation of vascular cells. Protein disulfide isomerase (PDI) is a thiol isomerase secreted from activated platelets and endothelial cells and plays a critical role in both platelet aggregation and fibrin generation. A number of potential intravascular targets of PDI have been identified including cell surface receptors (e...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29690612/neuroprotective-and-anti-inflammatory-effects-of-rhus-coriaria-extract-in-a-mouse-model-of-ischemic-optic-neuropathy
#7
Saba Khalilpour, Ghazaleh Behnammanesh, Fouad Suede, Mohammed O Ezzat, Jayadhisan Muniandy, Yasser Tabana, Mohamed Khadeer Ahamed, Ali Tamayol, Amin Malik Shah Majid, Enrico Sangiovanni, Mario Dell'Agli, Aman Shah Majid
Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria ( R. coriaria) extract in vivo. The half maximal inhibitory concentration (IC50 ) for DPPH, ABTS and β⁻carotene were 6.79 ± 0.009 µg/mL, 10.94 ± 0.09 µg/mL, and 6...
April 23, 2018: Biomedicines
https://www.readbyqxmd.com/read/29670459/neutrophils-release-metalloproteinases-during-adhesion-in-the-presence-of-insulin-but-cathepsin-g-in-the-presence-of-glucagon
#8
Natalia V Fedorova, Alexander L Ksenofontov, Marina V Serebryakova, Vladimir I Stadnichuk, Tatjana V Gaponova, Ludmila A Baratova, Galina F Sud'ina, Svetlana I Galkina
In patients with reperfusion after ischemia and early development of diabetes, neutrophils can attach to blood vessel walls and release their aggressive bactericide agents, which damage the vascular walls. Insulin and 17 β -estradiol (E2) relieve the vascular complications observed in metabolic disorders. In contrast, glucagon plays an essential role in the pathophysiology of diabetes. We studied the effect of hormones on neutrophil secretion during adhesion to fibronectin. Amino acid analysis revealed that proteins secreted by neutrophils are characterized by a stable amino acid profile enriched with glutamate, leucine, lysine, and arginine...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29664642/protease-specificity-profiling-in-a-pipette-tip-using-charge-synchronized-proteome-derived-peptide-libraries
#9
Minh T N Nguyen, Gerta Shema, René P Zahedi, Steven H L Verhelst
About 2% of the genome of human and other organisms codes for proteases. An important step toward deciphering the biological function of a protease and designing inhibitors is the profiling of protease specificity. In this work we present a novel, label-free, proteomics-based protease specificity profiling method that only requires simple sample preparation steps. It uses proteome-derived peptide libraries and enriches the cleaved sequences using strong cation exchange chromatography (SCX) material in a pipette tip...
April 17, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29662759/investigation-of-bioeffects-of-g-protein-coupled-receptor-1-on-bone-turnover-in-male-mice
#10
Jian Li, Liang Xiang, Xiaotong Jiang, Bin Teng, Yutao Sun, Guanlian Chen, Jie Chen, Jian V Zhang, Pei-Gen Ren
Maintenance of healthy bone quality and quantity requires a well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. Chemerin is a novel adipokine with known functions such as regulating immunity and energy homeostasis through activation of chemokine-like receptor 1 (CMKLR1). G protein-coupled receptor 1 (GPR1) is the second mammalian chemerin receptor with similar binding affinity as CMKLR1. In male GPR1-/- mice, a phenotype with significantly low bone mineral density was observed...
July 2017: Journal of Orthopaedic Translation
https://www.readbyqxmd.com/read/29652924/extended-cleavage-specificity-of-human-neutrophil-cathepsin-g-a-low-activity-protease-with-dual-chymase-and-tryptase-type-specificities
#11
Michael Thorpe, Zhirong Fu, Gurdeep Chahal, Srinivas Akula, Jukka Kervinen, Lawrence de Garavilla, Lars Hellman
Human neutrophils express at least four active serine proteases, cathepsin G, N-elastase, proteinase 3 and neutrophil serine protease 4 (NSP4). They have all been extensively studied due to their importance in neutrophil biology and immunity. However, their extended cleavage specificities have never been determined in detail. Here we present a detailed cleavage specificity analysis of human cathepsin G (hCG). The specificity was determined by phage display analysis and the importance of individual amino acids in and around the cleavage site was then validated using novel recombinant substrates...
2018: PloS One
https://www.readbyqxmd.com/read/29624387/computer-aided-discovery-and-characterization-of-novel-ebola-virus-inhibitors
#12
Stephen Joseph Capuzzi, Wei Sun, Eugene N Muratov, Carles Martinez-Romero, Shihua He, Wenjun Zhu, Hao Li, Gregory James Tawa, Ethan G Fisher, Miao Xu, Paul Shinn, Xiangguo Qiu, Adolfo García-Sastre, Wei Zheng, Alexander Tropsha
The Ebola virus (EBOV) causes severe human infection that lacks effective treatment. A recent screen identified a series of compounds that block EBOV-like particle entry into human cells. Using data from this screen, Quantitative Structure-Activity Relationship (QSAR) models were built and employed for virtual screening of a ~17 million compound library. Experimental testing of 102 hits yielded 14 compounds with IC50 values under 10 μM, including several sub-micromolar inhibitors, and more than 10-fold selectivity against host cytotoxicity...
April 6, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29621602/neutrophil-extracellular-traps-possess-anti-human-respiratory-syncytial-virus-activity-possible-interaction-with-the-viral-f-protein
#13
Priscila Silva Sampaio Souza, Lia Vezenfard Barbosa, Larissa Figueiredo Alves Diniz, Gabriel Soares da Silva, Bruno Rafael Pereira Lopes, Pedro Miyadaira Ribeiro Souza, Gabriela Campos de Araujo, Diogo Pessoa, Juliana de Oliveira, Fátima Pereira Souza, Karina Alves Toledo
Human respiratory syncytial virus (hRSV) is one of the main etiological agents of diseases of the lower respiratory tract, and is often responsible for the hospitalization of children and the elderly. To date, treatments are only palliative and there is no vaccine available. The airways of patients infected with hRSV exhibit intense neutrophil infiltration, which is responsible for the release of neutrophil extracellular traps (NETs). These are extracellular structures consisting of DNA associated with intracellular proteins, and are efficient in capturing and eliminating various microorganisms, including some viruses...
April 2, 2018: Virus Research
https://www.readbyqxmd.com/read/29616179/expression-and-localization-of-cathepsins-b-d-and-g-in-dupuytren-s-disease
#14
Kirin Tan, Helen D Brasch, Bede van Schaijik, James R Armstrong, Reginald W Marsh, Paul F Davis, Swee T Tan, Tinte Itinteang
Background: The pathogenesis of Dupuytren's disease (DD) remains unclear. An embryonic stem cell (ESC)-like population in the endothelium of the microvessels around tissues that expresses components of the renin-angiotensin system (RAS) has been reported. This study investigated if this primitive population expresses cathepsins B, D, and G, that contribute to RAS bypass loops. Methods: 3,3-Diaminobenzidine immunohistochemical (IHC) staining for cathepsins B, D, and G was performed on sections of formalin-fixed paraffin-embedded DD cords (n = 10) and nodules (n = 10)...
February 2018: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/29613789/design-and-synthesis-of-clinical-candidate-pf-06751979-a-potent-brain-penetrant-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-bace1-inhibitor-lacking-hypopigmentation
#15
Brian T O'Neill, Elizabeth M Beck, Christopher R Butler, Charles E Nolan, Cathleen Gonzales, Lei Zhang, Shawn D Doran, Kimberly Lapham, Leanne M Buzon, Jason K Dutra, Gabriela Barreiro, Xinjun Hou, Luis A Martinez-Alsina, Bruce N Rogers, Anabella Villalobos, John C Murray, Kevin Ogilvie, Erik A LaChapelle, Cheng Chang, Lorraine F Lanyon, Claire M Steppan, Ashley Robshaw, Katherine Hales, Germaine G Boucher, Karamjeet Pandher, Christopher Houle, Claude W Ambroise, David Karanian, David Riddell, Kelly R Bales, Michael A Brodney
A major challenge in the development of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors for the treatment of Alzheimer's disease is the alignment of potency, drug-like properties, and selectivity over related aspartyl proteases such as Cathepsin D (CatD) and BACE2. The potential liabilities of inhibiting BACE2 chronically has only recently begun to emerge as BACE2 impacts the processing of the premelanosome protein (PMEL17) and disrupts melanosome morphology resulting in a depigmentation phenotype...
April 3, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29601810/2-3-dihydroxy-5-methoxybiphenyl-suppresses-fmlp-induced-superoxide-anion-production-and-cathepsin-g-release-by-targeting-the-%C3%AE-subunit-of-g-protein-in-human-neutrophils
#16
Hsiang-Ruei Liao, Ih-Sheng Chen, Fu-Chao Liu, Shinn-Zhi Lin, Ching-Ping Tseng
This study investigates the effect and the underlying mechanism of 2',3-dihydroxy-5-methoxybiphenyl (RIR-2), a lignan extracted from the roots of Rhaphiolepis indica (L.) Lindl. ex Ker var. tashiroi Hayata ex Matsum. & Hayata (Rosaceae), on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced respiratory burst and cathepsin G in human neutrophils. Signaling pathways regulated by RIR-2 which modulated fMLP-induced respiratory burst were evaluated by an interaction between β subunit of G-protein (Gβ) with downstream signaling induced by fMLP and by immunoblotting analysis of the downstream targets of Gβ-protein...
March 27, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29571981/giardipain-1-a-protease-secreted-by-giardia-duodenalis-trophozoites-causes-junctional-barrier-and-apoptotic-damage-in-epithelial-cell-monolayers
#17
Guadalupe Ortega-Pierres, Raúl Argüello-García, Marco S Laredo-Cisneros, Rocío Fonseca-Linán, Misael Gómez-Mondragón, Rolando Inzunza-Arroyo, David Flores-Benítez, Arturo Raya-Sandino, Bibiana Chavez-Munguía, José Luis Ventura-Gallegos, Alejandro Zentella-Dehesa, Rosa María Bermúdez-Cruz, Lorenza González-Mariscal
The adhesion of Giardia duodenalis trophozoites to intestinal epithelial cells allows the onset and maintenance of giardiasis. During these interactions, epithelial cells can be committed to apoptosis by enzymes secreted by the parasites, including cysteine proteases that are increasingly identified as virulence factors in parasitic protozoa. In this work, a monoclonal antibody (mAb1G3) raised against G. duodenalis surface components was found to react with a 25 kDa protein expressed in the cell surface and flagella of G...
March 20, 2018: International Journal for Parasitology
https://www.readbyqxmd.com/read/29559387/endurance-exercise-mediates-neuroprotection-against-mptp-mediated-parkinson-s-disease-via-enhanced-neurogenesis-antioxidant-capacity-and-autophagy
#18
Yongchul Jang, Insu Kwon, Wankeun Song, Ludmila M Cosio-Lima, Youngil Lee
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra, leading to motor dysfunction. Growing evidence has demonstrated that endurance exercise (EE) confers neuroprotection against PD; However, the exact molecular mechanisms responsible for exercise-induced protection of dopaminergic neurons in PD remain unclear. Since oxidative stress plays a key role in the degenerative process of PD. We investigated whether EE-induced neuroprotection is associated with enhanced antioxidative capacity and autophagy, using a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration...
March 17, 2018: Neuroscience
https://www.readbyqxmd.com/read/29550006/ovariectomy-exacerbates-apical-periodontitis-in-rats-with-an-increase-in-expression-of-proinflammatory-cytokines-and-matrix-metalloproteinases
#19
Priscilla Coutinho Romualdo, Marília P Lucisano, Francisco Wanderley G Paula-Silva, Graziela B Leoni, Manoel D Sousa-Neto, Raquel Assed B Silva, Lea Assed B Silva, Paulo Nelson-Filho
INTRODUCTION: The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats. METHODS: Twenty 12-week-old female Wistar rats were subjected to ovariectomy (OVX) or sham surgery. After 9 weeks, access cavities were prepared in the maxillary and mandibular first molars, pulp tissue was removed, and canals were exposed to the oral environment during 21 days for the induction of AP...
May 2018: Journal of Endodontics
https://www.readbyqxmd.com/read/29547534/a-novel-betabaculovirus-isolated-from-the-monocot-pest-mocis-latipes-lepidoptera-noctuidae-and-the-evolution-of-multiple-copy-genes
#20
Daniel M P Ardisson-Araújo, Ana Maria Rodrigues da Silva, Fernando L Melo, Ethiane Rozo Dos Santos, Daniel R Sosa-Gómez, Bergmann M Ribeiro
In this report, we described the genome of a novel baculovirus isolated from the monocot insect pest Mocis latipes , the striped grass looper. The genome has 134,272 bp in length with a G + C content of 38.3%. Based on the concatenated sequence of the 38 baculovirus core genes, we found that the virus is a betabaculovirus closely related to the noctuid-infecting betabaculoviruses including Pseudaletia unipuncta granulovirus (PsunGV), Trichoplusia ni granulovirus (TnGV), Helicoverpa armigera granulovirus (HearGV), and Xestia c-nigrum granulovirus (XecnGV)...
March 16, 2018: Viruses
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