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Protease activated receptor 2

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https://www.readbyqxmd.com/read/28339772/heterologous-desensitization-of-cardiac-%C3%AE-adrenergic-signal-via-hormone-induced-%C3%AE-ar-arrestin-pde4-complexes
#1
Qian Shi, Minghui Li, Delphine Mika, Qin Fu, Sungjin Kim, Jason Phan, Ao Shen, Gregoire Vandecasteele, Yang K Xiang
Aims: Cardiac β-adrenergic receptor (βAR) signaling is susceptible to heterologous desensitization by different neurohormonal stimuli in clinical conditions associated with heart failure. We aim to examine the underlying mechanism of cross talk between βARs and a set of G-protein coupled receptors (GPCRs) activated by hormones/agonists. Methods and results: Rat ventricular cardiomyocytes were used to determine heterologous phosphorylation of βARs under a series of GPCR agonists...
February 21, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28335793/thrombus-leukocytes-exhibit-more-endothelial-cell-specific-angiogenic-markers-than-peripheral-blood-leukocytes-do-in-acute-coronary-syndrome-patients-suggesting-a-possibility-of-trans-differentiation-a-comprehensive-database-mining-study
#2
Hangfei Fu, Nish Vadalia, Eric R Xue, Candice Johnson, Luqiao Wang, William Y Yang, Claudette Sanchez, Jun Nelson, Qian Chen, Eric T Choi, Jian-Xing Ma, Jun Yu, Hong Wang, Xiaofeng Yang
BACKGROUND: Current angiogenic therapies for cancers and cardiovascular diseases have not yet achieved expected benefits, which reflects the need for improved understanding of angiogenesis. In this study, we focused on solving the problem of whether tissues have different angiogenic potentials (APs) in physiological conditions and how angiogenesis is regulated in various disease conditions. METHODS: In healthy and diseased human and mouse tissues, we profiled the expression of 163 angiogenic genes, including transcription regulators (TRs), growth factors and receptors (GF/Rs), cytokines and chemokines (C/Cs), and proteases and inhibitors (P/Is)...
March 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28323866/elevated-fecal-peptidase-d-at-onset-of-colitis-in-galphai2-mice-a-mouse-model-of-ibd
#3
Daniel Bergemalm, Robert Kruse, Maria Sapnara, Jonas Halfvarson, Elisabeth Hultgren Hörnquist
BACKGROUND: The identification of novel fecal biomarkers in inflammatory bowel disease (IBD) is hampered by the complexity of the human fecal proteome. On the other hand, in experimental mouse models there is probably less variation. We investigated the fecal protein content in mice to identify possible biomarkers and pathogenic mechanisms. METHODS: Fecal samples were collected at onset of inflammation in Galphai2-/- mice, a well-described spontaneous model of chronic colitis, and from healthy littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28316004/effect-of-the-fxa-inhibitors-rivaroxaban-and-apixaban-on-platelet-activation-in-patients-with-atrial-fibrillation
#4
B Steppich, F Dobler, L C Brendel, G Hessling, S L Braun, A L Steinsiek, I Deisenhofer, A Hyseni, M Roest, I Ott
Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study...
March 18, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#5
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28303089/protease-activated-receptor-2-par2-induces-long-term-depression-in-the-hippocampus-through-transient-receptor-potential-vanilloid-4-trpv4
#6
Efrat Shavit-Stein, Avital Artan-Furman, Ekaterina Feingold, Marina Ben Shimon, Zeev Itzekson-Hayosh, Joab Chapman, Andreas Vlachos, Nicola Maggio
Protease activated receptors (PARs) are involved in regulating synaptic transmission and plasticity in the brain. While it is well-accepted that PAR1 mediates long-term potentiation (LTP) of excitatory synaptic strength, the role of PAR2 in synaptic plasticity remains not well-understood. In this study, we assessed the role of PAR2-signaling in plasticity at hippocampal Schaffer collateral-CA1 synapses. Using field potential recordings, we report that PAR2-activation leads to long-term depression (LTD) of synaptic transmission through a protein kinase A -dependent, Transient Receptor Potential Vanilloid 4 -mediated mechanism, which requires the activation of N-methyl-D-aspartate receptors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28283478/annexin-a2-contributes-to-lung-injury-and-fibrosis-by-augmenting-factor-xa-fibrogenic-activity
#7
Michael Schuliga, Jade Jaffar, Asres Berhan, Shenna Langenbach, Trudi Harris, David Waters, Peter Vee Sin Lee, Christopher Grainge, Glen Westall, Darryl Knight, Alastair G Stewart
In lung injury and disease, including idiopathic pulmonary fibrosis (IPF), extravascular factor X is converted into factor Xa (FXa), a coagulant protease with fibrogenic actions. Extracellular annexin A2 binds to FXa, augmenting activation of the protease activated receptor-1 (PAR-1). In this study, the contribution of annexin A2 in lung injury and fibrosis was investigated. Annexin A2 immunoreactivity was observed in regions of fibrosis, including associated with fibroblasts in lung tissue of IPF patients...
March 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28267608/analysis-of-the-mirna-profile-in-c6-36-cells-persistently-infected-with-dengue-virus-type-2
#8
Rodolfo Gamaliel Avila-Bonilla, Martha Yocupicio-Monroy, Laurence A Marchat, Mónica A De Nova-Ocampo, Rosa María Del Ángel, Juan Santiago Salas-Benito
Dengue virus (DENV) is the most important arbovirus in the world; DENV is transmitted by the Aedes genus of mosquitoes and can establish a life-long persistent infection in mosquitoes. However, the exact mechanism by which persistent infection is established remains unknown. In this study the differential expression of miRNAs was analysed by deep sequencing and RT-qPCR using a previously established C6/36-HT cell line persistently infected with DENV 2 (C6-L) as a model. miR-927, miR-87, miR-210, miR-2a-3p, miR-190 and miR-970 were up-regulated, whereas miR-252, miR-263a-3p, miR-92b, miR-10-5p miR-9a-5p, miR-9a-1, miR-124, miR-286a and miR-286b were down-regulated in C6-L cells compared with C6/36 cells acutely infected with the same virus or mock-infected cells...
March 4, 2017: Virus Research
https://www.readbyqxmd.com/read/28267389/molecular-requirements-involving-the-human-platelet-protease-activated-receptor-4-mechanism-of-activation-by-peptide-analogues-of-its-tethered-ligand
#9
I C Moschonas, T F Kellici, T Mavromoustakos, P Stathopoulos, V Tsikaris, V Magafa, A G Tzakos, A D Tselepis
Thrombin is the most potent agonist of human platelets and its effects are primarily mediated through the protease-activated receptors (PARs)-1 and -4. Although PAR-1 has higher affinity for thrombin than PAR-4, both receptors contribute to thrombin-mediated actions on platelets. Recently, a potent and selective PAR-1 antagonist (vorapaxar) was approved for clinical use in selected patients. In contrast, despite the fact that several PAR-4 antagonists have been developed, few of them have been tested in clinical trials...
March 7, 2017: Platelets
https://www.readbyqxmd.com/read/28254587/activity-of-human-kallikrein-related-peptidase-6-klk6-on-substrates-containing-sequences-of-basic-amino-acids-is-it-a-processing-protease
#10
Roberta N Silva, Lilian C G Oliveira, Carolina B Parise, Juliana R Oliveira, Beatrice Severino, Angela Corvino, Paola di Vaio, Piero A Temussi, Giuseppe Caliendo, Vincenzo Santagada, Luiz Juliano, Maria A Juliano
Human kallikrein 6 (KLK6) is highly expressed in the central nervous system and with elevated level in demyelinating disease. KLK6 has a very restricted specificity for arginine (R) and hydrolyses myelin basic protein, protein activator receptors and human ionotropic glutamate receptor subunits. Here we report a previously unreported activity of KLK6 on peptides containing clusters of basic amino acids, as in synthetic fluorogenic peptidyl-Arg-7-amino-4-carbamoylmethylcoumarin (peptidyl-ACC) peptides and FRET peptides in the format of Abz-peptidyl-Q-EDDnp (where Abz=ortho-aminobenzoic acid and Q-EDDnp=glutaminyl-N-(2,4-dinitrophenyl) ethylenediamine), in which pairs or sequences of basic amino acids (R or K) were introduced...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28245472/role-of-protease-activated-receptor-2-in-regulating-focal-segmental-glomerulosclerosis
#11
Yongjun Wang, Yanfa He, Mingzheng Wang, Pei Lv, Jianzhen Liu, Junxia Wang
Background /Aims: The underlying mechanisms leading to focal segmental glomerulosclerosis (FSGS) are lacking. In this report, we examined the role of protease-activated receptors (PARs) subtype PAR2 and its downstream signals in regulating the pathophysiological process of FSGS. METHODS: Nephropathy was induced by intravenous injections of adriamycin (ADR) in rats to study FSGS. Western Blot analysis and ELISA were employed to determine the protein expression levels of PAR2 and its downstream signal pathways as well as the levels of PICs...
February 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28245465/astragaloside-alleviates-hepatic-fibrosis-function-via-par2-signaling-pathway-in-diabetic-rats
#12
Zhenchang Wang, Quanqiang Li, Mingpeng Xiang, Fengying Zhang, Dongyu Wei, Zhixi Wen, Ying Zhou
BACKGROUND/AIMS: Astragaloside (AGS) extracted from radix astragalin (Huangqi) has been considered to be beneficial to liver diseases. In this study, we examined the role played by AGS in alleviating hepatic fibrosis function via protease-activated receptor-2 (PAR2) mechanisms. We hypothesized that AGS affects PAR2 signaling pathway thereby improving hepatic function in rats with hepatic fibrosis induced by carbon tetrachloride (CCl4). We further hypothesized that AGS attenuates impaired hepatic function evoked by CCl4 to a greater degree in diabetic animals...
February 28, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28242761/ex-vivo-human-pancreatic-slice-preparations-offer-a-valuable-model-for-studying-pancreatic-exocrine-biology
#13
Tao Liang, Subhankar Dolai, Li Xie, Erin Winter, Abrahim I Orabi, Negar Karimian, Laura I Cosen-Binker, Ya-Chi Huang, Peter Thorn, Mark Cattral, Herbert Y Gaisano
A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathological responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28240259/circulating-cathepsin-s-levels-correlate-with-gfr-decline-and-stnfr1-and-stnfr2-levels-in-mice-and-humans
#14
Dominik Steubl, Santhosh V Kumar, Maia Tato, Shrikant R Mulay, Anders Larsson, Lars Lind, Ulf Risérus, Lutz Renders, Uwe Heemann, Axel C Carlsson, Johan Ärnlöv, Hans-Joachim Anders
Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804)...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28238749/persistent-kallikrein5-activation-induces-atopic-dermatitis-like-skin-architecture-independent-of-par2-activity
#15
Yanan Zhu, Joanne Underwood, Derek Macmillan, Leila Shariff, Ryan O'Shaughnessy, John I Harper, Chris Pickard, Peter S Friedmann, Eugene Healy, Wei-Li Di
BACKGROUND: Up-regulation of kallikreins (KLK) including KLK5 has been reported in atopic dermatitis (AD). KLK5 has biological functions which include degrading desmosomal proteins and inducing pro-inflammatory cytokine secretion through protease activated receptor 2 (PAR2). However, due to the complex interactions between various cells in AD inflamed skin, it is difficult to dissect the precise and multiple roles of up-regulated KLK5 in AD skin. OBJECTIVE: We investigated the effect of up-regulated KLK5 on the expression of epidermal related proteins and cytokines in keratinocytes and on skin architecture...
February 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28223242/fviia-prevents-the-progressive-hemorrhaging-of-a-brain-contusion-by-protecting-microvessels-via-formation-of-the-tf-fviia-fxa-complex
#16
Qiang Yuan, Dalong Zhang, Sirong Wu, Jian Yu, Lei Yu, Yirui Sun, Zhuoying Du, Zhiqi Li, Liangfu Zhou, Xing Wu, Jin Hu
Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant human activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions...
February 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28220880/parenteral-administration-of-factor-xa-iia-inhibitors-limits-experimental-aortic-aneurysm-and-atherosclerosis
#17
Corey S Moran, Sai-Wang Seto, Smriti M Krishna, Surabhi Sharma, Roby J Jose, Erik Biros, Yutang Wang, Susan K Morton, Jonathan Golledge
Intraluminal thrombus is a consistent feature of human abdominal aortic aneurysm (AAA). Coagulation factor Xa (FXa) catalyses FII to thrombin (FIIa). We examined the effect of FXa/FIIa inhibition on experimental aortic aneurysm in apolipoprotein E-deficient (ApoE(-/-)) mice infused with angiotensin II (AngII). The concentration of FXa within the supra-renal aorta (SRA) correlated positively with SRA diameter. Parenteral administration of enoxaparin (FXa/IIa inhibitor) and fondaparinux (FXa inhibitor) over 14 days reduced to severity of aortic aneurysm and atherosclerosis in AngII-infused ApoE(-/-) mice...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220122/nf-%C3%AE%C2%BAb-links-tlr2-and-par1-to-soluble-immunomodulator-factor-secretion-in-human-platelets
#18
Pauline Damien, Fabrice Cognasse, Bernard Payrastre, Sherry L Spinelli, Neil Blumberg, Charles-Antoine Arthaud, Marie-Ange Eyraud, Richard P Phipps, Archibald McNicol, Bruno Pozzetto, Olivier Garraud, Hind Hamzeh-Cognasse
The primary toll-like receptor (TLR)-mediated immune cell response pathway common for all TLRs is MyD88-dependent activation of NF-κB, a seminal transcription factor for many chemokines and cytokines. Remarkably, anucleate platelets express the NF-κB machinery, whose role in platelets remains poorly understood. Here, we investigated the contribution of NF-κB in the release of cytokines and serotonin by human platelets, following selective stimulation of TLR2 and protease activated receptor 1 (PAR1), a classical and non-classical pattern-recognition receptor, respectively, able to participate to the innate immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218251/stim1-phosphorylation-at-y361-recruits-orai1-to-stim1-puncta-and-induces-ca-2-entry
#19
Pascal Yazbeck, Mohammad Tauseef, Kevin Kruse, Md-Ruhul Amin, Rayees Sheikh, Stefan Feske, Yulia Komarova, Dolly Mehta
Store-operated Ca(2+) entry (SOCE) mediates the increase in intracellular calcium (Ca(2+)) in endothelial cells (ECs) that regulates several EC functions including tissue-fluid homeostasis. Stromal-interaction molecule 1 (STIM1), upon sensing the depletion of (Ca(2+)) from the endoplasmic reticulum (ER) store, organizes as puncta that trigger store-operated Ca(2+) entry (SOCE) via plasmalemmal Ca(2+)-selective Orai1 channels. While the STIM1 and Orai1 binding interfaces have been mapped, signaling mechanisms activating STIM1 recruitment of Orai1 and STIM1-Orai1 interaction remains enigmatic...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216875/antidermatophytic-and-protease-inhibiting-activities-of-zerumbone-a-natural-sesquiterpene-from-the-rhizome-of-zingiber-zerumbet-l-roscoe-ex-j-e-smith
#20
Madhavankutty Jyothilakshmi, Mathew Jyothis, Gokulanathan Nair Hari Narayanan, Mukalel Sankunni Latha
CONTEXT: Due to increase in the number of patients with impaired immunity, incidence of dermatophytoses has increased considerably. Antidermatophytic agents with anti-inflammatory and protease-inhibiting activities will help in restricting inflammatory response associated with dermatophytoses. AIMS: The present study aims to evaluate antidermatophytic and protease-inhibiting activities of zerumbone. Cytotoxicity was tested using Chang liver cell line as a preliminary step in toxicity study...
January 2017: Pharmacognosy Magazine
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