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Protease activated receptor

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https://www.readbyqxmd.com/read/29780528/synthetic-glycan-based-tlr4-agonists-targeting-caspase-4-11-for-the-development-of-adjuvants-and-immunotherapeutics
#1
Florian Adanitsch, Jianjin Shi, Feng Shao, Rudi Beyaert, Holger Heine, Alla Zamyatina
Gram-negative bacterial lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) mediated pro-inflammatory signaling plays a key role in immunoprotection against infectious challenges and boosts adaptive immunity, whereas the activation of the cytosolic LPS receptor caspase-4/11 leads to cell death by pyroptosis and is deeply implicated in the development of sepsis. Despite tremendous advances in the understanding of the LPS-TLR4 interaction, predictably regulated TLR4 activation has not yet been achieved...
April 28, 2018: Chemical Science
https://www.readbyqxmd.com/read/29778747/novel-peptide-inhibits-inflammation-by-suppressing-of-protease-activated-receptor-2
#2
Bora Kim, Hyun-Soo Kim
We synthesized and investigated the effects of a novel peptide B, RRFSLLRY as a novel PAR-2 antagonist. Peptide B decreased calcium levels in HaCat cells stimulated with trypsin and PAR-2 activator (SLIGKV) and cytokeratin 14 and PCNA was decreased by peptide B. Peptides B also reduced the expression of inflammatory cytokines such as TNF-α and interleukin-6. Significant increase of oxazolone-induced transepidermal water loss (TEWL) was decreased by the addition of peptide B in hairless mice. These findings suggest that the anti-inflammatory effect of peptide B is due to inhibition of PAR-2 signaling...
May 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29777666/analysis-of-cross-resistance-to-vip3-proteins-in-eight-insect-colonies-from-four-insect-species-selected-for-resistance-to-bacillus-thuringiensis-insecticidal-proteins
#3
Joaquín Gomis-Cebolla, Yuequin Wang, Yudong Quan, Kanglai He, Tom Walsh, Bill James, Sharon Downes, Wendy Kain, Ping Wang, Kathy Leonard, Tom Morgan, Brenda Oppert, Juan Ferré
Bacillus thuringiensis Vip3 proteins are synthesized and secreted during the vegetative growth phase. They are activated by gut proteases, recognize and bind to midgut receptors, form pores and lyse cells. We tested the susceptibility to Vip3Aa and Vip3Ca of Cry1A-, Cry2A-, Dipel- and Vip3-resistant insect colonies from different species to determine whether resistance to other insecticidal proteins confers cross-resistance to Vip3 proteins. As expected, the colonies resistant to Cry1A proteins, Dipel (Helicoverpa armigera, Trichoplusia ni, Ostrinia furnacalis and Plodia interpunctella) or Cry2Ab (H...
May 16, 2018: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/29777060/protease-activated-receptor-1-inhibits-cholesterol-efflux-and-promotes-atherogenesis-via-cullin-3-mediated-degradation-of-the-abca1-transporter
#4
Somasundaram Raghavan, Nikhlesh K Singh, Arul M Mani, Gadiparthi N Rao
Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin-Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3-mediated ubiquitination and degradation of ATP-binding cassette subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29775725/anti-hepatitis-c-virus-activity-and-synergistic-effect-of-nymphaea-alba-extracts-and-bioactive-constituents-in-liver-infected-cells
#5
Sidra Rehman, Usman Ali Ashfaq, Bushra Ijaz, Sheikh Riazuddin
BACKGROUND: Without an effective vaccine, hepatitis C virus (HCV) remains a global threat, inflicting 170-300 million carriers worldwide at risk of cirrhosis and hepatocellular carcinoma (HCC). Though various direct acting antivirals have been redeemed the hepatitis C treatment, a few restraints persist including possible side effects, viral resistance emergence, excessive cost which restricts its availability to a common person. HYPOTHESIS: There is no preventive HCV vaccine available today so the discovery of potent antiviral natural flora and their bioactive constituents may help to develop preventive cures against HCV infection...
May 15, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29774092/vorapaxar-treatment-reduces-mesangial-expansion-in-streptozotocin-induced-diabetic-nephropathy-in-mice
#6
Maaike Waasdorp, JanWillem Duitman, Sandrine Florquin, C Arnold Spek
Background: Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#7
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29769546/effects-of-the-th2-dominant-milieu-on-allergic-responses-in-der-f-1-activated-mouse-basophils-and-mast-cells
#8
Myung-Hee Yi, Hyoung-Pyo Kim, Kyoung Yong Jeong, Ju Yeong Kim, In-Yong Lee, Tai-Soon Yong
Although basophils and mast cells share similar phenotypic and functional properties, little is known about the difference in the initial Th2 immune responses of these cells following exposure to proteolytic allergens. Here, we investigated the mechanisms of Th2-mediated immune responses in mouse bone marrow-derived basophils (BMBs) and mast cells (BMMCs) via stimulation with the cysteine protease allergen Der f 1. Our results showed that Th2 cytokines were induced from BMBs by active recombinant Der f 1 (rDer f 1 independently with Toll-like receptor (TLR) 2 and TLR4...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#9
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29763961/the-novel-protease-activated-receptor-1-antagonist-vorapaxar-as-a-treatment-for-thrombosis-in-afibrinogenemia
#10
Bernard Tawfik, Elizabeth Pollard, Yu-Min Shen
No abstract text is available yet for this article.
May 15, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29760696/podosomes-but-not-the-maturation-status-determine-the-protease-dependent-3d-migration-in-human-dendritic-cells
#11
Céline Cougoule, Claire Lastrucci, Romain Guiet, Rémi Mascarau, Etienne Meunier, Geanncarlo Lugo-Villarino, Olivier Neyrolles, Renaud Poincloux, Isabelle Maridonneau-Parini
Dendritic cells (DC) are professional Antigen-Presenting Cells scattered throughout antigen-exposed tissues and draining lymph nodes, and survey the body for pathogens. Their ability to migrate through tissues, a 3D environment, is essential for an effective immune response. Upon infection, recognition of Pathogen-Associated Molecular Patterns (PAMP) by Toll-like receptors (TLR) triggers DC maturation. Mature DC (mDC) essentially use the protease-independent, ROCK-dependent amoeboid mode in vivo , or in collagen matrices in vitro ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760600/comprehensive-proteome-analysis-of-nasal-lavage-samples-after-controlled-exposure-to-welding-nanoparticles-shows-an-induced-acute-phase-and-a-nuclear-receptor-lxr-rxr-activation-that-influence-the-status-of-the-extracellular-matrix
#12
Neserin Ali, Stefan Ljunggren, Helen M Karlsson, Aneta Wierzbicka, Joakim Pagels, Christina Isaxon, Anders Gudmundsson, Jenny Rissler, Jörn Nielsen, Christian H Lindh, Monica Kåredal
Background: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed...
2018: Clinical Proteomics
https://www.readbyqxmd.com/read/29760175/modulation-of-receptor-protein-tyrosine-phosphatase-sigma-increases-chondroitin-sulfate-proteoglycan-degradation-through-cathepsin-b-secretion-to-enhance-axon-outgrowth
#13
Amanda Phuong Tran, Sapna Sundar, Meigen Yu, Bradley T Lang, Jerry Silver
Severed axon tips reform growth cones following spinal cord injury that fail to regenerate, in part, because they become embedded within an inhibitory extracellular matrix. Chondroitin sulfate proteoglycans (CSPGs) are the major axon inhibitory matrix component that is increased within the lesion scar and in perineuronal nets around deafferented neurons. We have recently developed a novel peptide modulator (Intracellular Sigma Peptide or ISP) of the cognate receptor of CSPGs, protein tyrosine phosphatase sigma (RPTPσ), which has been shown to markedly improve sensorimotor function, micturition, and coordinated locomotor behavior in spinal cord contused rats...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29751765/lipophilic-components-of-diesel-exhaust-particles-induce-pro-inflammatory-responses-in-human-endothelial-cells-through-ahr-dependent-pathway-s
#14
Bendik C Brinchmann, Tonje Skuland, Mia H Rambøl, Krisztina Szoke, Jan E Brinchmann, Arno C Gutleb, Elisa Moschini, Alena Kubátová, Klara Kukowski, Eric Le Ferrec, Dominique Lagadic-Gossmann, Per E Schwarze, Marit Låg, Magne Refsnes, Johan Øvrevik, Jørn A Holme
BACKGROUND: Exposure to traffic-derived particulate matter (PM), such as diesel exhaust particles (DEP), is a leading environmental cause of cardiovascular disease (CVD), and may contribute to endothelial dysfunction and development of atherosclerosis. It is still debated how DEP and other inhaled PM can contribute to CVD. However, organic chemicals (OC) adhered to the particle surface, are considered central to many of the biological effects. In the present study, we have explored the ability of OC from DEP to reach the endothelium and trigger pro-inflammatory reactions, a central step on the path to atherosclerosis...
May 11, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29749311/role-of-the-ldl-receptor-related-protein-1-in-regulating-protease-activity-and-signaling-pathways-in-the-vasculature
#15
Dianaly T Au, Allison L Arai, William E Fondrie, Selen C Muratoglu, Dudley K Strickland
Aortic aneurysms represent a significant clinical problem as they largely go undetected until a rupture occurs. Currently, an understanding of mechanisms leading to aneurysm formation is limited. Numerous studies clearly indicate that vascular smooth muscle cells play a major role in the development and response of the vasculature to hemodynamic changes and defects in these responses can lead to aneurysm formation. The LDL receptor-related protein 1 (LRP1) is major smooth muscle cell receptor that has the capacity to mediate the endocytosis of numerous ligands and to initiate and regulate signaling pathways...
May 11, 2018: Current Drug Targets
https://www.readbyqxmd.com/read/29748334/genetic-variant-in-human-par-protease-activated-receptor-4-enhances-thrombus-formation-resulting-in-resistance-to-antiplatelet-therapeutics
#16
Benjamin E Tourdot, Hannah Stoveken, Derek Trumbo, Jennifer Yeung, Yogendra Kanthi, Leonard C Edelstein, Paul F Bray, Gregory G Tall, Michael Holinstat
OBJECTIVE: Platelet activation after stimulation of PAR (protease-activated receptor) 4 is heightened in platelets from blacks compared with those from whites. The difference in PAR4 signaling by race is partially explained by a single-nucleotide variant in PAR4 encoding for either an alanine or threonine at amino acid 120 in the second transmembrane domain. The current study sought to determine whether the difference in PAR4 signaling by this PAR4 variant is because of biased Gq signaling and whether the difference in PAR4 activity results in resistance to traditional antiplatelet intervention...
May 10, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29744290/identification-of-small-molecule-elastase-inhibitors-as-antagonists-of-il-36-cytokine-activation
#17
Graeme P Sullivan, Pavel B Davidovich, Sylvia Sura-Trueba, Ekaterina Belotcerkovskaya, Conor M Henry, Danielle M Clancy, Anna Zinoveva, Tazhir Mametnabiev, Alexander V Garabadzhiu, Seamus J Martin
IL-1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL-36α, IL-36β and IL-36γ, which belong to the extended IL-1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL-36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL-36 receptor antagonist result in a severe form of psoriasis...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29743547/the-protease-activated-receptor2-promotes-rab5a-mediated-generation-of-pro-metastatic-microvesicles
#18
Kaushik Das, Ramesh Prasad, Sreetama Roy, Ashis Mukherjee, Prosenjit Sen
Metastasis, the hallmark of cancer propagation is attributed by the modification of phenotypic/functional behavior of cells to break attachment and migrate to distant body parts. Cancer cell-secreted microvesicles (MVs) contribute immensely in disease propagation. These nano-vesicles, generated from plasma membrane outward budding are taken up by nearby healthy cells thereby inducing phenotypic alterations in those recipient cells. Protease activated receptor 2 (PAR2), activated by trypsin, also contributes to cancer progression by increasing metastasis, angiogenesis etc...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29739329/thrombin-and-factor-xa-link-the-coagulation-system-with-liver-fibrosis
#19
Ameet Dhar, Fouzia Sadiq, Quentin M Anstee, Adam P Levene, Robert D Goldin, Mark R Thursz
BACKGROUND: Thrombin activates hepatic stellate cells via protease-activated receptor-1. The role of Factor Xa (FXa) in hepatic fibrosis has not been elucidated. We aimed to evaluate the impact of FXa and thrombin in vitro on stellate cells and their respective inhibition in vivo using a rodent model of hepatic fibrosis. METHODS: HSC-LX2 cells were incubated with FXa and/or thrombin in cell culture, stained for αSMA and relative gene expression and gel contraction calculated...
May 8, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29735342/dabigatran-reduces-endothelial-permeability-through-inhibition-of-thrombin-induced-cytoskeleton-reorganization
#20
Hyun-Jung Choi, Na-Eun Kim, Jayoung Kim, Sunho An, Seung-Hee Yang, Jimin Ha, Sunghee Cho, Il Kwon, Young Dae Kim, Hyo Suk Nam, Ji Hoe Heo
Dabigatran etexilate (DE), a new oral anti-coagulant, is a direct thrombin inhibitor. Clinical trials showed the favorable benefit-to-risk profile of DE compared to warfarin for the prevention of ischemic stroke in patients with atrial fibrillation. Remarkably, patients treated with dabigatran showed reduced rates of intracerebral hemorrhage compared to warfarin. As the breakdown of endothelial barrier integrity is associated with hemorrhagic events and as thrombin increases endothelial permeability, we hypothesized that dabigatran preserves the endothelial barrier by inhibiting thrombin-induced permeability...
April 25, 2018: Thrombosis Research
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