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Protease activated receptor

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https://www.readbyqxmd.com/read/28198394/cockroach-protease-allergen-induces-allergic-airway-inflammation-via-epithelial-cell-activation
#1
Sagar L Kale, Komal Agrawal, Shailendra Nath Gaur, Naveen Arora
Protease allergens are known to enhance allergic inflammation but their exact role in initiation of allergic reactions at mucosal surfaces still remains elusive. This study was aimed at deciphering the role of serine protease activity of Per a 10, a major cockroach allergen in initiation of allergic inflammation at mucosal surfaces. We demonstrate that Per a 10 increases epithelial permeability by disruption of tight junction proteins, ZO-1 and occludin, and enhances the migration of Monocyte derived dendritic cell precursors towards epithelial layer as exhibited by trans-well studies...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28195946/g-protein-coupled-receptor-mediated-transactivation-of-extracellular-proteases
#2
Allison E Schafer, Burns C Blaxall
G protein-coupled receptors (GPCRs) comprise the largest family of receptors in humans. Traditional activation of GPCRs involves binding of a ligand to the receptor, activation of heterotrimeric G proteins and induction of subsequent signaling molecules. It is now known that GPCR signaling occurs through G protein-independent pathways including signaling through β-arrestin as well as transactivation of other receptor types. Generally, transactivation occurs when activation of one receptor leads to the activation of another receptor(s)...
February 13, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28191683/immediate-type-allergic-and-protease-mediated-reactions-are-involved-in-scratching-behavior-induced-by-topical-application-of-dermatophagoides-farinae-extract-in-nc-nga-mice
#3
Yoshihito Yamada, Yuhki Ueda, Aki Nakamura, Shoji Kanayama, Rie Tamura, Kei Hashimoto, Tatsumi Matsumoto, Ritsuko Ishii
Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behavior after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behavior in each phase. An increase in the content of mast cell derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28187433/doxycycline-directly-targets-par1-to-suppress-tumor-progression
#4
Weilong Zhong, Shuang Chen, Qiang Zhang, Ting Xiao, Yuan Qin, Ju Gu, Bo Sun, Yanrong Liu, Xiangyan Jing, Xuejiao Hu, Peng Zhang, Honggang Zhou, Tao Sun, Cheng Yang
Doxycycline have been reported to exert anti-cancer activity and have been assessed as anti-cancer agents in clinical trials. However, the direct targets of doxycycline in cancer cells remain unclear. In this study, we used a chemical proteomics approach to identify the Protease-activated receptor 1 (PAR1) as a specific target of inhibition of doxycycline. Binding assays and single-molecule imaging assays were performed to confirm the inhibition of doxycycline to PAR1. The effect of doxycycline on multi-omics and cell functions were assessed based on a PAR1/thrombin model...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28182192/dabigatran-potentiates-gemcitabine-induced-growth-inhibition-of-pancreatic-cancer-in-mice
#5
Kun Shi, Helene Damhofer, Joost Daalhuisen, Marieke Ten Brink, Dick J Richel, C Arnold Spek
Pancreatic cancer is one of the most lethal solid malignancies with little treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives progression and induces chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we addressed the effect of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth whereas it significantly increased tumor dissemination throughout the peritoneal cavity...
February 6, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28179529/differential-disruption-of-nucleocytoplasmic-trafficking-pathways-by-rhinovirus-2a-proteases
#6
Kelly Watters, Bahar Inankur, Jaye C Gardiner, Jay Warrick, Nathan M Sherer, John Yin, Ann C Palmenberg
The RNA rhinoviruses (RV) encode 2A proteases (2A(pro)) that contribute essential polyprotein processing and host-cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A(pro) sequences which act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98 and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A(pro) predict RV genotype-specific targeting of NPC pathways and cargos...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179493/nutritional-and-lipid-modulation-of-pcsk9-effects-on-cardiometabolic-risk-factors
#7
REVIEW
Jacqueline A Krysa, Teik Chye Ooi, Spencer D Proctor, Donna F Vine
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B lipoprotein cholesterol metabolism. Hepatic PCSK9 protein expression, activity, and secretion have been shown to affect cholesterol homeostasis. An upregulation of hepatic PSCK9 protein leads to increased LDLR degradation, resulting in decreased uptake of apoB lipoproteins and a consequent increase in the plasma concentration of these lipoproteins, including LDL and chylomicron remnants...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28179423/xanthine-dehydrogenase-1-silencing-in-aedes-aegypti-mosquitoes-promotes-a-blood-feeding-induced-adulticidal-activity
#8
Jun Isoe, Natthida Petchampai, Yurika E Isoe, Katrina Co, Stacy Mazzalupo, Patricia Y Scaraffia
Aedesaegypti has 2 genes encoding xanthine dehydrogenase (XDH). We analyzed XDH1 and XDH2 gene expression by real-time quantitative PCR in tissues from sugar- and blood-fed females. Differential XDH1 and XDH2 gene expression was observed in tissues dissected throughout a time course. We next exposed females to blood meals supplemented with allopurinol, a well-characterized XDH inhibitor. We also tested the effects of injecting double-stranded RNA (dsRNA) against XDH1, XDH2, or both. Disruption of XDH by allopurinol or XDH1 by RNA interference significantly affected mosquito survival, causing a disruption in blood digestion, excretion, oviposition, and reproduction...
February 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28177892/pevonedistat-a-nedd8-activating-enzyme-inhibitor-sensitizes-neoplastic-b-cells-to-death-receptor-mediated-apoptosis
#9
Cody Paiva, J Claire Godbersen, Taylor Rowland, Olga V Danilova, Christopher Danes, Allison Berger, Alexey V Danilov
While death receptor ligands (Fas and TRAIL) kill chemoresistant tumor cell lines, related therapies have limited clinical efficacy as single agents. Death receptor signaling is modulated by nuclear factor-κB (NFκB), a family of transcription factors which are constitutively active in B-cell malignancies. We and others have shown that pevonedistat, an investigational inhibitor of the NEDD8-activating enzyme, abrogates NFκB activity in B-cell neoplasia. Here we demonstrate that diffuse large B-cell lymphoma, particularly activated B-cell type, and primary chronic lymphocytic leukemia cells are re-sensitized to extrinsic apoptosis by pevonedistat...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28173772/potential-importance-of-protease-activated-receptor-par-1-expression-in-the-tumor-stroma-of-non-small-cell-lung-cancer
#10
Cong Lin, Christof J Majoor, Joris J T H Roelofs, Martijn D de Kruif, Hugo M Horlings, Keren Borensztajn, C Arnold Spek
BACKGROUND: Protease activated receptor (PAR)-1 expression is increased in a variety of tumor cells. In preclinical models, tumor cell PAR-1 appeared to be involved in the regulation of lung tumor growth and metastasis; however the role of PAR-1 in the lung tumor microenvironment, which is emerging as a key compartment in driving cancer progression, remained to be explored. METHODS: In the present study, PAR-1 gene expression was determined in lung tissue from patients with non-small-cell lung cancer (NSCLC) using a combination of publicly available RNA microarray datasets and in house-made tissue microarrays including tumor biopsies of 94 patients with NSCLC (40 cases of adenocarcinoma, 42 cases of squamous cell carcinoma and 12 cases of other type of NSCLC at different stages)...
February 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28169521/biased-signaling-by-peptide-agonists-of-protease-activated-receptor-2
#11
Yuhong Jiang, Mei-Kwan Yau, W Mei Kok, Junxian Lim, Kai-Chen Wu, Ligong Liu, Timothy A Hill, Jacky Y Suen, David P Fairlie
Protease activated receptor 2 (PAR2) is associated with metabolism, obesity, inflammatory, respiratory and gastrointestinal disorders, pain, cancer and other diseases. The extracellular N-terminus of PAR2 is a common target for multiple proteases, which cleave it at different sites to generate different N-termini that activate different PAR2-mediated intracellular signaling pathways. There are no synthetic PAR2 ligands that reproduce the same signaling profiles and potencies as proteases. Structure-activity relationships here for 26 compounds spanned a signaling bias over 3 log units, culminating in three small ligands as biased agonist tools for interrogating PAR2 functions...
February 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28166283/metalloproteinase-9-contributes-to-endothelial-dysfunction-in-atherosclerosis-via-protease-activated-receptor-1
#12
Jon M Florence, Agnieszka Krupa, Laela M Booshehri, Timothy C Allen, Anna K Kurdowska
The atherosclerotic process begins when vascular endothelial cells undergo pro-inflammatory changes such as aberrant activation to dysfunctional phenotypes and apoptosis, leading to loss of vascular integrity. Our laboratory has demonstrated that exposure of mice to second hand smoke triggers an increase in expression of metalloproteinase-9. Further, metalloproteinase-9 released by second hand smoke-activated leukocytes may propagate pro-atherogenic alterations in endothelial cells. We have shown that levels of metalloproteinase-9 were increased in the plasma from apolipoprotein E deficient (ApoE-/-) mice exposed to second hand smoke relative to non-exposed controls...
2017: PloS One
https://www.readbyqxmd.com/read/28164807/induction-of-b7-h1-receptor-by-bacterial-cells-fractions-of-porphyromonas-gingivalis-on-human-oral-epithelial-cells-b7-h1-induction-by-porphyromonas-gingivalis-fractions
#13
S Groeger, F Jarzina, U Mamat, J Meyle
The immune-regulatory B7-H1 receptor, also known as programmed death-ligand 1 (PD-L1), plays an important role in cell-mediated immune response. It is a co-signaling molecule that mediates regulation of T cell activation and tolerance and is able to negatively regulate activated T cell functions and survival. High expression of B7-H1 in host cells may contribute to the chronicity of inflammatory disorders and represents a possible mechanism of immune evasion. Porphyromonas gingivalis is regarded as a keystone pathogen in periodontitis and is able to invade host cells and disposes a variety of virulence factors including lipopolysaccharide (LPS), fimbriae and proteases such as gingipains...
February 2017: Immunobiology
https://www.readbyqxmd.com/read/28162529/-292-protease-activated-receptor-2-par2-is-a-mediator-of-nociception-in-a-mouse-model-of-migraine
#14
S Hassler, T Price, G Dussor, S Boitano, J Vagner
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28161438/molecular-and-evolutionary-perspectives-of-the-renin-angiotensin-system-from-lamprey
#15
Marty K S Wong, Yoshio Takei
The recent advance and revision on the renin-angiotensin system in lamprey were summarized and we emphasized that presence of two types of angiotensins (Angs) in lamprey. Due to the parasitic nature on fish blood, teleost-type Angs were produced in their buccal gland and secreted into the lamphredin to evade the host immunorejection. A native lamprey angiotensinogen (AGT) was identified in genome and it retains serine-protease inhibitor activity for thrombin that regulates the blood coagulation pathway. The native lamprey angiotensin II (Lp-Ang II) is hypotensive instead of hypertensive, suggesting a functional divergence on cardiovascular regulation from the main vertebrate groups...
February 2, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28160743/dioxolanea3-phosphatidylethanolamines-are-generated-by-human-platelets-and-stimulate-neutrophil-integrin-expression
#16
Maceler Aldrovandi, Christine Hinz, Sarah N Lauder, Helen Podmore, Martin Hornshaw, David A Slatter, Victoria J Tyrrell, Stephen R Clark, Lawrence J Marnett, Peter W Collins, Robert C Murphy, Valerie B O'Donnell
Activated platelets generate an eicosanoid proposed to be 8-hydroxy-9,10-dioxolane A3 (DXA3). Herein, we demonstrate that significant amounts of DXA3 are rapidly attached to phosphatidylethanolamine (PE) forming four esterified eicosanoids, 16:0p, 18:0p, 18:1p and 18:0a/DXA3-PEs that can activate neutrophil integrin expression. These lipids comprise the majority of DXA3 generated by platelets, are formed in ng amounts (24.3±6.1ng/2×10(8)) and remain membrane bound. Pharmacological studies revealed DXA3-PE formation involves cyclooxygenase-1 (COX), protease-activated receptors (PAR) 1 and 4, cytosolic phospholipase A2 (cPLA2), phospholipase C and intracellular calcium...
January 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28160627/interleukin-11-driven-gastric-tumourigenesis-is-independent-of-trans-signalling
#17
Jesse J Balic, Christoph Garbers, Stefan Rose-John, Liang Yu, Brendan J Jenkins
Deregulated gp130-dependent STAT3 signalling by the pleiotropic cytokine interleukin (IL)-11 has been implicated in the pathogenesis of gastric cancer (GC), the third most common cancer worldwide. While the IL-11-gp130-STAT3 signalling axis has traditionally been thought to exclusively use the membrane-bound IL-11 receptor (mIL-11R), recent evidence suggests that mIL-11R can be proteolytically cleaved to generate a soluble form (sIL-11R) which can elicit trans-signalling. Since the role of IL-11 trans-signalling in disease pathogenesis is unknown, here we have employed the IL-11-driven gp130(F/F) spontaneous model of GC to determine whether IL-11 trans-signalling promotes gastric tumourigenesis...
February 1, 2017: Cytokine
https://www.readbyqxmd.com/read/28159824/novel-thrombolytic-drug-based-on-thrombin-cleavable-microplasminogen-coupled-to-a-single-chain-antibody-specific-for-activated-gpiib-iiia
#18
Thomas Bonnard, Zachary Tennant, Be'Eri Niego, Ruchi Kanojia, Karen Alt, Shweta Jagdale, Lok Soon Law, Sheena Rigby, Robert Lindsay Medcalf, Karlheinz Peter, Christoph Eugen Hagemeyer
BACKGROUND: Thrombolytic therapy for acute thrombosis is limited by life-threatening side effects such as major bleeding and neurotoxicity. New treatment options with enhanced fibrinolytic potential are therefore required. Here, we report the development of a new thrombolytic molecule that exploits key features of thrombosis. We designed a recombinant microplasminogen modified to be activated by the prothrombotic serine-protease thrombin (HtPlg), fused to an activation-specific anti-glycoprotein IIb/IIIa single-chain antibody (SCE5), thereby hijacking the coagulation system to initiate thrombolysis...
February 3, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28159725/topical-treatments-of-saussurea-costus-root-and-thuja-orientalis-l-synergistically-alleviate-atopic-dermatitis-like-skin-lesions-by-inhibiting-protease-activated-receptor-2-and-nf-%C3%AE%C2%BAb-signaling-in-hacat-cells-and-nc-nga-mice
#19
Hye Jeong Yang, Min Jung Kim, Suna Kang, Na Rang Moon, Da Sol Kim, Na Ra Lee, Kang Sung Kim, Sunmin Park
ETHNOPHARMACOLOGICAL RELEVANCE: The root of Saussurea costus (Aucklandia lappa Decne, Aucklandiae Radix, SC) and Thuja orientalis L. (TOL) have been traditionally used as anti-inflammatory agents in Korea. However, they have not been studied for the efficacy of atopic dermatitis (AD) treatment, a chronic inflammatory skin disease. We investigated the efficacy of topical applications with 1,3-butyleneglycol extracts of SC and TOL to alleviate the symptoms of AD. MATERIALS AND METHODS: HaCaT cells and the dorsal skin of Nc/Nga mice had a local exposure of house mite extracts and 2,4-dinitrochlorobenzene (DNCB), respectively...
January 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28152299/development-of-a-reporter-system-for-in-vivo-monitoring-of-%C3%AE-secretase-activity-in-drosophila
#20
Young Gi Hong, Seyun Roh, Donggi Paik, Sangyun Jeong
The γ-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the β-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the γ-secretase catalytic component, presenilin, which lead to increased amyloid βpeptide production, are responsible for early-onset familial Alzheimer's disease. β-amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of γ-secretase activity...
January 2017: Molecules and Cells
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