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Protease activated receptor

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https://www.readbyqxmd.com/read/28350991/serum-proteases-potentiate-bmp-induced-cell-cycle-re-entry-of-dedifferentiating-muscle-cells-during-newt-limb-regeneration
#1
Ines Wagner, Heng Wang, Philipp M Weissert, Werner L Straube, Anna Shevchenko, Marc Gentzel, Goncalo Brito, Akira Tazaki, Catarina Oliveira, Takuji Sugiura, Andrej Shevchenko, András Simon, David N Drechsel, Elly M Tanaka
Limb amputation in the newt induces myofibers to dedifferentiate and re-enter the cell cycle to generate proliferative myogenic precursors in the regeneration blastema. Here we show that bone morphogenetic proteins (BMPs) and mature BMPs that have been further cleaved by serum proteases induce cell cycle entry by dedifferentiating newt muscle cells. Protease-activated BMP4/7 heterodimers that are present in serum strongly induced myotube cell cycle re-entry with protease cleavage yielding a 30-fold potency increase of BMP4/7 compared with canonical BMP4/7...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28345958/macrophage-elastase-induces-trail-mediated-tumor-cell-death-through-its-carboxyterminal-domain
#2
Nadine Dandachi, Neil J Kelly, John P Wood, Christine L Burton, Josiah E Radder, Adriana S Leme, Alyssa D Gregory, Steven D Shapiro
RATIONALE: Macrophage elastase (MMP12) is a potent protease that contributes to the lung destruction that accompanies cigarette smoking while it simultaneously inhibits lung tumor angiogenesis and metastasis by catalyzing the formation of anti-angiogenic peptides. Recent studies have revealed novel non-proteolytic functions of MMP12, including antimicrobial activity through a peptide within its C-terminal domain (CTD). OBJECTIVES: Our objective was to determine whether the MMP12 CTD contributes to its anti-tumor activity in lung cancer...
March 27, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28344073/role-of-thrombin-par1-pkc%C3%AE-%C3%AE-axis-in-brain-pericytes-in-thrombin-induced-mmp-9-production-and-blood-brain-barrier-dysfunction-in-vitro
#3
Takashi Machida, Shinya Dohgu, Fuyuko Takata, Junichi Matsumoto, Ikuya Kimura, Mariko Koga, Keiko Nakamoto, Atsushi Yamauchi, Yasufumi Kataoka
Thrombin, an essential component in the coagulation cascade, participates in the pathogenesis of brain diseases, such as ischemic stroke, intracerebral hemorrhage, Alzheimer's disease and Parkinson's disease through blood-brain barrier (BBB) dysfunction. It is thought that the thrombin-matrix metalloproteinase (MMP)-9 axis is an important process in the pathogenesis of neurovascular disease, such as BBB dysfunction. We recently reported that brain pericytes are the most MMP-9-releasing cells in response to thrombin stimulation among the BBB-constituting cells...
March 23, 2017: Neuroscience
https://www.readbyqxmd.com/read/28342149/identification-and-preparation-of-a-novel-chemokine-receptor-binding-domain-in-the-cytoplasmic-regulator-frount
#4
Akihiro Sonoda, Sosuke Yoshinaga, Kaori Yunoki, Soichiro Ezaki, Kotaro Yano, Mitsuhiro Takeda, Etsuko Toda, Yuya Terashima, Kouji Matsushima, Hiroaki Terasawa
FROUNT is a cytoplasmic protein that binds to the membrane-proximal C-terminal regions (Pro-Cs) of chemokine receptors, CCR2 and CCR5. The FROUNT-chemokine receptor interactions play a pivotal role in the migration of inflammatory immune cells, indicating the potential of FROUNT as a drug target for inflammatory diseases. To provide the foundation for drug development, structural information of the Pro-C binding region of FROUNT is desired. Here, we defined the novel structural domain (FNT-CB), which mediates the interaction with the chemokine receptors...
March 24, 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28339772/heterologous-desensitization-of-cardiac-%C3%AE-adrenergic-signal-via-hormone-induced-%C3%AE-ar-arrestin-pde4-complexes
#5
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
#6
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/28332048/histamine-release-from-mast-cells-and-basophils
#7
Francesco Borriello, Raffaella Iannone, Gianni Marone
Mast cells and basophils represent the most relevant source of histamine in the immune system. Histamine is stored in cytoplasmic granules along with other amines (e.g., serotonin), proteases, proteoglycans, cytokines/chemokines, and angiogenic factors and rapidly released upon triggering with a variety of stimuli. Moreover, mast cell and basophil histamine release is regulated by several activating and inhibitory receptors. The engagement of different receptors can trigger different modalities of histamine release and degranulation...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28325877/dual-utility-nls-drives-rnf169-dependent-dna-damage-responses
#8
Liwei An, Yiyang Jiang, Howin H W Ng, Ellen P S Man, Jie Chen, Ui-Soon Khoo, Qingguo Gong, Michael S Y Huen
Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair. ring finger protein 169 (RNF169) maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged chromatin. We report here that this attribute is accomplished, in part, by a predicted nuclear localization signal (NLS) that not only shuttles RNF169 into the nucleus but also promotes its stability by mediating a direct interaction with the ubiquitin-specific protease USP7...
March 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28323866/elevated-fecal-peptidase-d-at-onset-of-colitis-in-galphai2-mice-a-mouse-model-of-ibd
#9
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/28322979/3-4-methylenedioxymethamphetamine-mdma-ecstasy-produces-edema-due-to-bbb-disruption-induced-by-mmp-9-activation-in-rat-hippocampus
#10
Mercedes Pérez-Hernández, María Encarnación Fernández-Valle, Ana Rubio-Araiz, Rebeca Vidal, María Dolores Gutiérrez-López, Esther O'Shea, María Isabel Colado
The recreational drug of abuse, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) disrupts blood-brain barrier (BBB) integrity in rats through an early P2X7 receptor-mediated event which induces MMP-9 activity. Increased BBB permeability often causes plasma proteins and water to access cerebral tissue leading to vasogenic edema formation. The current study was performed to examine the effect of a single neurotoxic dose of MDMA (12.5 mg/kg, i.p.) on in vivo edema development associated with changes in the expression of the perivascular astrocytic water channel, AQP4, as well as in the expression of the tight-junction (TJ) protein, claudin-5 and Evans Blue dye extravasation in the hippocampus of adult male Dark Agouti rats...
March 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28316004/effect-of-the-fxa-inhibitors-rivaroxaban-and-apixaban-on-platelet-activation-in-patients-with-atrial-fibrillation
#11
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
#12
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/28306665/molecular-mechanisms-that-mediate-invasion-and-egress-of-malaria-parasites-from-red-blood-cells
#13
Aditi Alaganan, Pallavi Singh, Chetan E Chitnis
PURPOSE OF REVIEW: Malaria parasites invade and multiply in diverse host cells during their complex life cycle. Some blood stage parasites transform into male and female gametocytes that are transmitted by female anopheline mosquitoes. The gametocytes are activated in the mosquito midgut to form male and female gametes, which egress from RBCs to mate and form a zygote. Here, we will review our current understanding of the molecular mechanisms that mediate invasion and egress by malaria parasites at different life cycle stages...
March 16, 2017: Current Opinion in Hematology
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
#14
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/28302665/calpain-mobilizes-atg9-bif-1-vesicles-from-golgi-stacks-upon-autophagy-induction-by-thapsigargin
#15
Elena Marcassa, Marzia Raimondi, Tahira Anwar, Eeva-Liisa Eskelinen, Michael P Myers, Gianluca Triolo, Claudio Schneider, Francesca Demarchi
CAPNS1 is essential for stability and function of the ubiquitous calcium dependent proteases micro- and milli-calpain. Upon the inhibition of the endoplasmic reticulum Ca2+ ATPase by 100nM thapsigargin, both micro-calpain and autophagy are activated in human U2OS osteosarcoma cells in a CAPNS1 dependent manner. As reported for other autophagy triggers, thapsigargin treatment induces Golgi fragmentation and fusion of Atg9/Bif-1 containing vesicles with LC3 bodies in control cells. On the opposite, CAPNS1 depletion is coupled to an accumulation of LC3 bodies and Rab5 early endosomes...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28296821/protease-activated-receptor-1-plays-a-proinflammatory-role-in-colitis-by-promoting-th17-related-immunity
#16
Muhammad A Saeed, Garrett Z Ng, Jan Däbritz, Josef Wagner, Louise Judd, Jia-Xi Han, Poshmaal Dhar, Carl D Kirkwood, Philip Sutton
BACKGROUND: Proteolytic cleavage of protease-activated receptor 1 (PAR1) can result in potent downstream regulatory effects on inflammation. Although PAR1 is expressed throughout the gastrointestinal tract and activating proteases are increased in inflammatory bowel disease, the effect of PAR1 activation on colitis remains poorly understood, and has not previously been studied in pediatric disease. METHODS: Expression of PAR1 and inflammatory cytokines in colonic biopsies from pediatric patients with Crohn's disease exhibiting active moderate to severe colitis was measured by quantitative PCR...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28294177/rational-design-of-protein-c-activators
#17
Sergio Barranco-Medina, Mary Murphy, Leslie Pelc, Zhiwei Chen, Enrico Di Cera, Nicola Pozzi
In addition to its procoagulant and proinflammatory functions mediated by cleavage of fibrinogen and PAR1, the trypsin-like protease thrombin activates the anticoagulant protein C in a reaction that requires the cofactor thrombomodulin and the endothelial protein C receptor. Once in the circulation, activated protein C functions as an anticoagulant, anti-inflammatory and regenerative factor. Hence, availability of a protein C activator would afford a therapeutic for patients suffering from thrombotic disorders and a diagnostic tool for monitoring the level of protein C in plasma...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28293890/characterizing-dynamic-protein-protein-interactions-using-the-genetically-encoded-split-biosensor-assay-technique-split-tev
#18
Jan P Wintgens, Moritz J Rossner, Michael C Wehr
Dynamic protein-protein interactions (PPIs) are fundamental building blocks of cellular signaling and monitoring their regulation promotes the understanding of signaling in health and disease. Genetically encoded split protein biosensor assays, such as the split TEV method, have proved to be highly valuable when studying regulated PPIs in living cells. Split TEV is based on the functional complementation of two previously inactive TEV protease fragments fused to interacting proteins and provides a robust, sensitive and flexible readout to monitor PPIs both at the membrane and in the cytosol...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28293889/engineering-and-characterizing-synthetic-protease-sensors-and-switches
#19
Viktor Stein, Kirill Alexandrov
Proteases are finding an increasing number of applications as molecular tools and reporters in biotechnology and basic research. Proteases are also increasingly incorporated into synthetic genetic signaling circuits equipping cells with tailored new functions. In the majority of cases however, proteases are employed in constitutively active forms which limits their utility and application as molecular sensors. The following chapter provides a detailed experimental protocol for converting constitutively active proteases into regulated protease receptors...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#20
REVIEW
Rahul Chaudhary, Jalaj Garg, Neeraj Shah, Andrew Sumner
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia...
February 26, 2017: World Journal of Cardiology
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