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https://www.readbyqxmd.com/read/28545251/oxidative-stress-promoter-of-allergic-sensitization-to-protease-allergens
#1
REVIEW
Leonie S van Rijt, Lara Utsch, René Lutter, Ronald van Ree
Allergies arise from aberrant T helper type 2 responses to allergens. Several respiratory allergens possess proteolytic activity, which has been recognized to act as an adjuvant for the development of a Th2 response. Allergen source-derived proteases can activate the protease-activated receptor-2, have specific effects on immune cells by cleaving cell membrane-bound regulatory molecules, and can disrupt tight junctions. The protease activity can induce a non-allergen-specific inflammatory response in the airways, which will set the stage for an allergen-specific Th2 response...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#2
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28541292/long-range-allosteric-regulation-of-the-human-26s-proteasome-by-20s-proteasome-targeting-cancer-drugs
#3
David Haselbach, Jil Schrader, Felix Lambrecht, Fabian Henneberg, Ashwin Chari, Holger Stark
The proteasome holoenzyme is the major non-lysosomal protease; its proteolytic activity is essential for cellular homeostasis. Thus, it is an attractive target for the development of chemotherapeutics. While the structural basis of core particle (CP) inhibitors is largely understood, their structural impact on the proteasome holoenzyme remains entirely elusive. Here, we determined the structure of the 26S proteasome with and without the inhibitor Oprozomib. Drug binding modifies the energy landscape of conformational motion in the proteasome regulatory particle (RP)...
May 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28540665/different-molecular-mechanisms-mediate-direct-or-glia-dependent-prion-protein-fragment-90-231-neurotoxic-effects-in-cerebellar-granule-neurons
#4
Stefano Thellung, Elena Gatta, Francesca Pellistri, Valentina Villa, Alessandro Corsaro, Mario Nizzari, Mauro Robello, Tullio Florio
Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrP(Sc)). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca(++)] i increase...
May 25, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#5
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533492/anti-tumor-activity-of-anthrax-toxin-variants-that-form-a-functional-translocation-pore-by-intermolecular-complementation
#6
Shihui Liu, Qian Ma, Rasem Fattah, Thomas H Bugge, Stephen H Leppla
Anthrax lethal toxin is a typical A-B type protein toxin secreted by Bacillus anthracis. Lethal factor (LF) is the catalytic A-subunit, a metalloprotease having MEKs as targets. LF relies on the cell-binding B-subunit, protective antigen (PA), to gain entry into the cytosol of target cells. PA binds to cell surface toxin receptors and is activated by furin protease to form an LF-binding-competent oligomer-PA pre-pore, which converts to a functional protein-conductive pore in the acidic endocytic vesicles, allowing translocation of LF into the cytosol...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28532656/the-il-33-st2-axis-is-crucial-in-type-2-airway-responses-induced-by-the-staphylococcus-aureus-protease-spld
#7
Andrea R Teufelberger, Maria Nordengrün, Harald Braun, Tania Maes, Katrien De Grove, Gabriele Holtappels, Clara O'Brien, Sharen Provoost, Hamida Hammad, Amanda Gonçalves, Rudi Beyaert, Wim Declercq, Peter Vandenabeele, Dmitri V Krysko, Barbara M Bröker, Claus Bachert, Olga Krysko
BACKGROUND: Chronic airway inflammatory diseases such as chronic rhinosinusitis with nasal polyps and asthma showed increased nasal Staphylococcus aureus (S. aureus) colonization. Serine protease like protein D (SplD) and other closely related proteases secreted by S. aureus have recently been identified as inducers of allergic asthma in humans and mice but their mechanism of action is largely unknown. OBJECTIVE: We investigated the role of recombinant SplD in driving Th2-biased responses and IgE formation in a murine model of allergic asthma...
May 19, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28526008/cleavage-of-the-urokinase-receptor-upar-on-oral-cancer-cells-regulation-by-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-and-potential-effects-on-migration-and-invasion
#8
Synnove Norvoll Magnussen, Elin Hadler-Olsen, Daniela Elena Costea, Eli Berg, Cristiane Cavalcanti Jacobsen, Bente Mortensen, Tuula Salo, Inigo Martinez-Zubiaurre, Jan-Olof Winberg, Lars Uhlin-Hansen, Gunbjorg Svineng
BACKGROUND: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion...
May 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28525362/fgf21-receptor-agonists-an-emerging-therapeutic-class-for-obesity-related-diseases
#9
Junichiro Sonoda, Mark Z Chen, Amos Baruch
Fibroblast growth factor 21 (FGF21) analogs and FGF21 receptor agonists (FGF21RAs) that mimic FGF21 ligand activity constitute the new "FGF21-class" of anti-obesity and anti-diabetic molecules that improve insulin sensitivity, ameliorate hepatosteatosis and promote weight loss. The metabolic actions of FGF21-class proteins in obese mice are attributed to stimulation of brown fat thermogenesis and increased secretion of adiponectin. The therapeutic utility of this class of molecules is being actively investigated in clinical trials for the treatment of type 2 diabetes and non-alcoholic steatohepatitis (NASH)...
May 19, 2017: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#10
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Asis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most vulnerable causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well-established that apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
May 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28521469/licochalcone-e-induces-caspase-dependent-death-of-human-pharyngeal-squamous-carcinoma-cells-through-the-extrinsic-and-intrinsic-apoptotic-signaling-pathways
#11
Sang-Joun Yu, In-A Cho, Kyeong-Rok Kang, Yi-Ra Jung, Seung Sik Cho, Goo Yoon, Ji-Su Oh, Jae-Seek You, Yo-Seob Seo, Gyeong-Je Lee, Sook-Young Lee, Do Kyung Kim, Chun Sung Kim, Su-Gwan Kim, Mi-Ae Jeong, Jae-Sung Kim
The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28516446/a-primary-human-lung-alveolus-on-a-chip-model-of-intravascular-thrombosis-for-assessment-of-therapeutics
#12
Abhishek Jain, Riccardo Barrile, Andries D van der Meer, Akiko Mammoto, Tadanori Mammoto, Karen De Ceunynck, Omozuanvbo Aisiku, Monicah A Otieno, Calvert S Louden, Geraldine A Hamilton, Robert Flaumenhaft, Donald E Ingber
Pulmonary thrombosis is a significant cause of patient mortality, however, there are no effective in vitro models of thrombi formation in human lung microvessels, that could also assess therapeutics and toxicology of antithrombotic drugs. Here we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium, and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis...
May 17, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28515717/the-leaderless-bacteriocin-enterocin-k1-is-highly-potent-against-enterococcus-faecium-a-study-on-structure-target-spectrum-and-receptor
#13
Kirill V Ovchinnikov, Per Eugen Kristiansen, Daniel Straume, Marianne S Jensen, Tamara Aleksandrzak-Piekarczyk, Ingolf F Nes, Dzung B Diep
Enterocin K1 (EntK1), enterocin EJ97 (EntEJ97), and LsbB are three sequence related leaderless bacteriocins. Yet LsbB kills only lactococci while EntK1 and EntEJ97 target wider spectra with EntK1 being particularly active against Enterococcus faecium, including nosocomial multidrug resistant isolates. NMR study of EntK1 showed that it had a structure very similar to LsbB - both having an amphiphilic N-terminal α-helix and an unstructured C-terminus. The α-helix in EntK1 is, however, about 3-4 residues longer than that of LsbB...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28512454/new-insights-into-the-regulation-of-cell-surface-signaling-activity-acquired-from-a-mutagenesis-screen-of-the-pseudomonas-putida-iuty-sigma-anti-sigma-factor
#14
Karlijn C Bastiaansen, Cristina Civantos, Wilbert Bitter, María A Llamas
Cell-surface signaling (CSS) is a signal transfer system that allows Gram-negative bacteria to detect environmental signals and generate a cytosolic response. These systems are composed of an outer membrane receptor that senses the inducing signal, an extracytoplasmic function sigma factor (σ(ECF)) that targets the cytosolic response by modifying gene expression and a cytoplasmic membrane anti-sigma factor that keeps the σ(ECF) in an inactive state in the absence of the signal and transduces its presence from the outer membrane to the cytosol...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28510269/kallikrein-related-peptidase-4-induces-cancer-associated-fibroblast-features-in-prostate-derived-stromal-cells
#15
T Kryza, L M Silva, N Bock, R A Fuhrman-Luck, C R Stephens, J Gao, H Samaratunga, M G Lawrence, J D Hooper, Y Dong, G P Risbridger, J A Clements
The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intra-epithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peri-stromal interface...
May 16, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28506571/tumor-necrosis-factor-receptor-associated-factor-traf-6-inhibition-mitigates-the-pro-inflammatory-roles-and-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#16
Lang-Jing Zhu, Tie-Cheng Yang, Qiang Wu, Li-Ping Yuan, Zhen-Wei Chen, Min-Hong Luo, Hai-Ou Zeng, Dong-Ling He, Cai-Ju Mo
BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs...
May 12, 2017: Cytokine
https://www.readbyqxmd.com/read/28502593/meprin-metalloproteases-molecular-regulation-and-function-in-inflammation-and-fibrosis
#17
REVIEW
Philipp Arnold, Anna Otte, Christoph Becker-Pauly
The zinc-endopeptidases meprin α and meprin β are extracellular proteases involved in connective tissue homeostasis, intestinal barrier function and immunological processes. Meprins are unique amongst other extracellular proteases with regard to cleavage specificity and structure. Meprin α and meprin β have a strong preference for negatively charged amino acids around the scissile bond, reflected by cleavage sites identified in procollagen I, the amyloid precursor protein (APP) and the interleukin-6 receptor (IL-6R)...
May 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28496990/mtorc1-regulates-mannose-6-phosphate-receptor-transport-and-t-cell-vulnerability-to-regulatory-t-cells-by-controlling-kinesin-kif13a
#18
Khawaja Ashfaque Ahmed, Jim Xiang
Mannose-6-phosphate receptor (M6PR) that facilitates cellular uptake of M6P-bearing proteins, including serine-protease granzyme-B (Gzm-B) has an important role in T-cell activation, migration and contraction. However, molecular mechanisms controlling M6PR expression in T cells remain poorly understood. Here, we show that M6PR expression on T cells is distinctively controlled by two common γ-chain cytokines interleukin-2 (IL-2) and IL-7, and the differential M6PR expression is not caused by an altered synthesis of M6PR protein, but is a result of distinct regulation of kinesin-3 motor-protein KIF13A that transport M6PR onto cell surfaces...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28493507/pkc-erk-p38-map-kinases-and-nf-%C3%AE%C2%BAb-targeted-signalling-play-a-role-in-the-expression-and-release-of-il-1%C3%AE-and-cxcl8-in-porphyromonas-gingivalis-infected-thp1-cells
#19
Kartheyaene Jayaprakash, Isak Demirel, Sezin Gunaltay, Hazem Khalaf, Torbjörn Bengtsson
Porphyromonas gingivalis is a keystone pathogen in periodontitis and is gaining importance in cardiovascular pathogenesis. Protease-activated receptors (PARs), toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD) on monocytes recognize the structural components on P. gingivalis, inducing inflammatory intermediates. Here, we elucidate the modulation of PARs, TLRs, NODs, and the role of MAPK and NF-κB in IL-1β and CXCL8 release. THP1 cells were stimulated with P. gingivalis wild-type W50 and its isogenic gingipain mutants: Rgp mutant E8 and Kgp mutant K1A...
May 11, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28491140/tryptase-mast-cell-density-protease-activated-receptor-2-microvascular-density-and-classical-microvascular-density-evaluation-in-gastric-cancer-patients-undergoing-surgery-possible-translational-relevance
#20
Michele Ammendola, Rosario Sacco, Giuseppina Vescio, Valeria Zuccalà, Maria Luposella, Rosa Patruno, Nicola Zizzo, Claudia Gadaleta, Ilaria Marech, Roberta Ruggieri, Ibrahim Furkan Kocak, Taner Ozgurtas, Cosmo Damiano Gadaleta, Giuseppe Sammarco, Girolamo Ranieri
BACKGROUND: Mast cells (MCs) can stimulate angiogenesis, releasing several proangiogenic cytokines stored in their cytoplasm. In particular, MCs can release tryptase, a potent in vivo and in vitro proangiogenic factor via protease-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. Nevertheless, no data are available concerning the relationship among tryptase MC density (TMCD), endothelial cells (ECs) positive to PAR-2 microvascular density (PAR-2-MVD) and classical MVD (C-MVD) in gastric cancer (GC) angiogenesis...
April 2017: Therapeutic Advances in Gastroenterology
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