keyword
MENU ▼
Read by QxMD icon Read
search

Protease activated receptor 2

keyword
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#1
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938454/11%C3%AE-hsd2-sumoylation-modulates-cortisol-induced-mineralocorticoid-receptor-nuclear-translocation-independently-of-effects-on-transactivation
#2
Rubén Jiménez-Canino, Fabián Lorenzo-Díaz, Alex Odermatt, Matthew A Bailey, Dawn E W Livingstone, Frederic Jaisser, Nicolette Farman, Diego Alvarez de la Rosa
The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) has an essential role in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor (MR) by converting 11β-hydroxyglucocorticoids to inactive 11-ketosteroids. Congenital deficiency of 11β-HSD2 causes a form of salt-sensitive hypertension known as the syndrome of apparent mineralocorticoid excess. The disease phenotype, which ranges from mild to severe, correlates well with reduction in enzyme activity. Furthermore, polymorphisms in the 11β-HSD2 coding gene (HSD11B2) have been linked to high blood pressure and salt-sensitivity, major cardiovascular risk factors...
September 15, 2017: Endocrinology
https://www.readbyqxmd.com/read/28924232/infection-of-microglia-with-porphyromonas-gingivalis-promotes-cell-migration-and-an-inflammatory-response-through-the-gingipain-mediated-activation-of-protease-activated-receptor-2-in-mice
#3
Yicong Liu, Zhou Wu, Yurika Nakanishi, Junjun Ni, Yoshinori Hayashi, Fumiko Takayama, Yanmin Zhou, Tomoko Kadawaki, Hiroshi Nakanishi
Despite a clear correlation between periodontitis and cognitive decline in Alzheimer's disease, the precise mechanism underlying the relationship remains unclear. The periodontal pathogen Porphyromonas gingivalis produces a unique class of cysteine proteinases termed gingipains that comprises Arg-gingipain (Rgp) and Lys-gingipain (Kgp). Rgp and Kgp are important in the bacterial mediated host cell responses and the subsequent intracellular signaling in infected cells. In the present study, we attempted to clarify the potential effects of Rgp and Kgp on the cellular activation of brain-resident microglia...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28921694/protease-activated-receptor-2-controls-myelin-development-resiliency-and-repair
#4
Hyesook Yoon, Maja Radulovic, Grant Walters, Alex R Paulsen, Kristen Drucker, Phillip Starski, Jianmin Wu, David P Fairlie, Isobel A Scarisbrick
Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood...
September 18, 2017: Glia
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#5
Li-Mei Chen, Karl X Chai
The epithelial extracellular membrane-associated serine proteases matriptase, hepsin, and prostasin are proteolytic modifying enzymes of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR). Matriptase also cleaves the ECD of the vascular endothelial growth factor receptor 2 (VEGFR2) and the angiopoietin receptor Tie2. In this study we tested the hypothesis that these serine proteases may cleave the ECD of additional receptor tyrosine kinases (RTKs). We co-expressed the proteases in an epithelial cell line with Her2, Her3, Her4, insulin receptor (INSR), insulin-like growth factor I receptor (IGF-1R), the platelet-derived growth factor receptors (PDGFRs) α and β, or nerve growth factor receptor A (TrkA)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912497/selective-antibody-activation-through-protease-activated-pro-antibodies-that-mask-binding-sites-with-inhibitory-domains
#6
I-Ju Chen, Chih-Hung Chuang, Yuan-Chin Hsieh, Yun-Chi Lu, Wen-Wei Lin, Chien-Chiao Huang, Ta-Chun Cheng, Yi-An Cheng, Kai-Wen Cheng, Yeng-Tseng Wang, Fang-Ming Chen, Tian-Lu Cheng, Shey-Cherng Tzou
Systemic injection of therapeutic antibodies may cause serious adverse effects due to on-target toxicity to the antigens expressed in normal tissues. To improve the targeting selectivity to the region of disease sites, we developed protease-activated pro-antibodies by masking the binding sites of antibodies with inhibitory domains that can be removed by proteases that are highly expressed at the disease sites. The latency-associated peptide (LAP), C2b or CBa of complement factor 2/B were linked, through a substrate peptide of matrix metalloproteinase-2 (MMP-2), to an anti-epidermal growth factor receptor (EGFR) antibody and an anti-tumor necrosis factor-α (TNF-α) antibody...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911209/intracellular-activation-of-ovastacin-mediates-pre-fertilization-hardening-of-the-zona-pellucida
#7
Hagen Körschgen, Michael Kuske, Konstantin Karmilin, Irene Yiallouros, Melanie Balbach, Julia Floehr, Dagmar Wachten, Willi Jahnen-Dechent, Walter Stöcker
STUDY QUESTION: How and where is pro-ovastacin activated and how does active ovastacin regulate zona pellucida hardening (ZPH) and successful fertilization? STUDY FINDING: Ovastacin is partially active before exocytosis and pre-hardens the zona pellucida (ZP) before fertilization. WHAT IS KNOWN ALREADY: The metalloproteinase ovastacin is stored in cortical granules, it cleaves zona pellucida protein 2 (ZP2) upon fertilization and thereby destroys the ZP sperm ligand and triggers ZPH...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28903918/-pro-renin-receptor-mediates-albumin-induced-cellular-responses-role-of-site-1-protease-derived-soluble-pro-renin-receptor-in-renal-epithelial-cells
#8
Hui Fang, Chuanming Xu, Aihua Lu, Chang-Jiang Zou, Shiying Xie, Yanting Chen, Li Zhou, Mi Liu, Lei Wang, Weidong Wang, Tianxin Yang
Proteinuria is a characteristic of chronic kidney disease (CKD) and also a causative factor that promotes the disease progression in part via activation of intrarenal renin-angiotensin system (RAS). (Pro) renin receptor (PRR), a newly discovered component of the RAS, binds renin and (pro) renin to promote angiotensin I generation. The present study was performed to test the role of soluble PRR (sPRR) in albumin overload-induced responses in cultured human renal proximal tubular cell line HK-2 cells. Bovine serum albumin (BSA) treatment for 24 h at 20 mg/ml induced renin activity and inflammation, both of which were attenuated by a PRR decoy inhibitor PRO20...
September 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28893914/stenotrophomonas-maltophilia-serine-protease-stmpr1-induces-matrilysis-anoikis-and-protease-activated-receptor-2-activation-in-human-lung-epithelial-cells
#9
Ashley L DuMont, Nicholas P Cianciotto
Stenotrophomonas maltophilia is an emerging, opportunistic nosocomial pathogen that can cause severe disease in immunocompromised individuals. We recently identified the StmPr1 and StmPr2 serine proteases as substrates of the Xps type II secretion system in S. maltophilia strain K279a. Here, we report that a third serine protease, StmPr3, is also secreted in an Xps-dependent manner. By constructing a panel of protease mutants in strain K279s, we were able to determine that StmPr3 contributes to the previously described Xps-mediated rounding and detachment of the A549 human lung epithelial cell line as well as Xps-mediated degradation of fibronectin, fibrinogen, and the cytokine interleukin-8...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28889362/a-novel-aza-mbp-altered-peptide-ligand-for-the-treatment-of-experimental-autoimmune-encephalomyelitis
#10
Nicole N M Trager, Jonathan T Butler, Jennifer Harmon, Joshua Mount, Maria Podbielska, Azizul Haque, Naren L Banik, Craig C Beeson
Myelin basic protein (MBP) is a major target of T cells in lesions of multiple sclerosis (MS) patients and its animal model, experimental autoimmune encephalomyelitis (EAE). Interactions between the major histocompatibility complex II containing antigenic peptides and the T cell receptor activate CD4+ T cells that perpetuate EAE and MS. Previously reported data has shown that treating with an altered peptide ligand (APL) in which the normal antigenic peptide sequence of MBP has been slightly changed at T cell contact positions is helpful in reducing disease in both rodents and humans...
September 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28883694/cytoplasmic-domain-of-tissue-factor-promotes-liver-fibrosis-in-mice
#11
Virginia Knight, Dinushka Lourensz, Jorge Tchongue, Jeanne Correia, Peter Tipping, William Sievert
AIM: To evaluate the role of tissue factor (TF) and protease activated receptor (PAR)-2 in liver fibrosis. METHODS: Using CCl4 administration for eight weeks, we induced hepatic fibrosis in wild-type C57BL/6 mice and in mice with deletion of the cytoplasmic signalling domain of TF (TF(§CT/§CT)), deletion of PAR-2 (PAR-2(-/-)) and combined deletion of TF signalling domain and PAR-2 (TF(§CT/§CT)/PAR-2(-/-)). Hepatic fibrosis area was assessed by quantitative imaging of picrosirius red staining...
August 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28883515/factor-xa-mediates-calcium-flux-in-endothelial-cells-and-is-potentiated-by-igg-from-patients-with-lupus-and-or-antiphospholipid-syndrome
#12
Bahar Artim-Esen, Natalia Smoktunowicz, Thomas McDonnell, Vera M Ripoll, Charis Pericleous, Ian Mackie, Eifion Robinson, David Isenberg, Anisur Rahman, Yiannis Ioannou, Rachel C Chambers, Ian Giles
Factor (F) Xa reactive IgG isolated from patients with antiphospholipid syndrome (APS) display higher avidity binding to FXa with greater coagulant effects compared to systemic lupus erythematosus (SLE) non APS IgG. FXa signalling via activation of protease-activated receptors (PAR) leads to increased intracellular calcium (Ca(2+)). Therefore, we measured alterations in Ca(2+) levels in human umbilical vein endothelial cells (HUVEC) following FXa-mediated PAR activation and investigated whether FXa reactive IgG from patients with APS or SLE/APS- alter these responses...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881236/investigating-detailed-interactions-between-novel-par1-antagonist-f16357-and-the-receptor-using-docking-and-molecular-dynamic-simulations
#13
Carolyn Readmond, Chun Wu
Currently, Vorapaxar is the only recently FDA-approved antiplatelet drug targeting Protease-activated receptor 1 (PAR1). However, a novel antagonist, F16357, has been shown to prevent painful bladder syndrome, also known as interstitial cystitis (IC). Unfortunately, there is no high resolution structure of the F16357-receptor complex, hindering its optimization as a therapeutic agent. In this study, we used docking and molecular dynamic (MD) simulations to investigate the detailed interactions between F16357 and PAR1 at a molecular level...
August 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28881035/protease-activated-receptor-2-contributes-to-toxoplasma-gondii-mediated-gut-inflammation
#14
Chrystelle Bonnart, Guylène Feuillet, Virginie Vasseur, Nicolas Cenac, Nathalie Vergnolle, Nicolas Blanchard
Toxoplasma gondii is a widespread intracellular parasite, which naturally enters the organism via the oral route and cross the intestinal barrier to disseminate. In addition to neuronal and ocular pathologies, this pathogen also causes gut inflammation in a number of animals. This infection-triggered inflammation has been extensively studied in the C57BL/6 mice, highlighting the importance of the immune cells and their mediators in the development of gut pathology. However, despite their importance in inflammation, the role of Protease-Activated Receptors (PAR) was never reported in the context of T...
September 7, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28877931/prostaglandin-e2-inhibits-histamine-evoked-ca2-release-in-human-aortic-smooth-muscle-cells-through-hyperactive-camp-signalling-junctions-and-protein-kinase-a
#15
Emily J A Taylor, Evangelia Pantazaka, Kathryn L Shelley, Colin W Taylor
In human aortic smooth muscle cells (ASMC), prostaglandin E2 (PGE2) stimulates adenylyl cyclase (AC) and attenuates the increase in intracellular free Ca(2+) concentration ([Ca(2+)]i) evoked by activation of histamine H1 receptors. The mechanisms are not resolved. We show that cAMP mediates inhibition of histamine-evoked Ca(2+) signals by PGE2 Exchange proteins activated by cAMP (EPACs) were not required, but the effects were attenuated by inhibition of cAMP-dependent protein kinase (PKA). PGE2 had no effect on the Ca(2+) signals evoked by protease-activated receptors, heterologously expressed muscarinic M3 receptors, or by direct activation of inositol 1,4,5-trisphosphate (IP3) receptors by photolysis of caged IP3 The rate of Ca(2+) removal from the cytosol was unaffected by PGE2, but PGE2 attenuated histamine-evoked IP3 accumulation...
September 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28875999/a-comparison-of-the-human-and-mouse-protein-corona-profiles-of-functionalized-sio2-nanocarriers
#16
A Solorio-Rodríguez, V Escamilla-Rivera, M Uribe-Ramírez, A Chagolla, R Winkler, C M García-Cuellar, A De Vizcaya-Ruiz
Nanoparticles are a promising cancer therapy for their use as drug carriers given their versatile functionalization with polyethylene glycol and proteins that can be recognized by overexpressed receptors in tumor cells. However, it has been suggested that in biological fluids, proteins cover nanoparticles, which gives the proteins a biological identity that could be responsible for unexpected biological responses: the so-called protein corona. A relevant biological event that is usually ignored in protein-corona formation is the interspecies differences in protein binding, which can be involved in the discrepancies observed in preclinical studies and the nanoparticle safety and efficiency...
September 21, 2017: Nanoscale
https://www.readbyqxmd.com/read/28874747/transcriptome-analysis-of-inflammation-related-gene-expression-in-endothelial-cells-activated-by-complement-masp-1
#17
Endre Schwaner, Zsuzsanna Németh, Péter K Jani, Erika Kajdácsi, Márta L Debreczeni, Zoltán Doleschall, József Dobó, Péter Gál, János Rigó, Kinga András, Tamás Hegedűs, László Cervenak
Mannan-binding lectin-associated serine protease 1 (MASP-1), the most abundant enzyme of the complement lectin pathway, is able to stimulate human umbilical vein endothelial cells (HUVECs) to alter the expression of several cytokines and adhesion molecules. This study has assessed to what extent MASP-1 is able to modify the transcriptional pattern of inflammation-related (IR) genes in HUVECs. We utilized Agilent microarray to analyse the effects of recombinant MASP-1 (rMASP-1) in HUVECs, on a set of 884 IR genes...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874459/protease-activated-receptor-2-activates-airway-apical-membrane-chloride-permeability-and-increases-ciliary-beating
#18
Derek B McMahon, Alan D Workman, Michael A Kohanski, Ryan M Carey, Jenna R Freund, Benjamin M Hariri, Bei Chen, Laurel J Doghramji, Nithin D Adappa, James N Palmer, David W Kennedy, Robert J Lee
Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl(-) current...
September 5, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28870093/novel-series-of-1-2-4-trioxane-derivatives-as-antimalarial-agents
#19
Mithun Rudrapal, Dipak Chetia, Vineeta Singh
Among three series of 1,2,4-trioxane derivatives, five compounds showed good in vitro antimalarial activity, three compounds of which exhibited better activity against P. falciparum resistant (RKL9) strain than the sensitive (3D7) one. Two best compounds were one from aryl series and the other from heteroaryl series with IC50 values of 1.24 µM and 1.24 µM and 1.06 µM and 1.17 µM, against sensitive and resistant strains, respectively. Further, trioxane derivatives exhibited good binding affinity for the P...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28866823/neuroprotective-effects-of-baicalein-on-acrolein-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-of-rat-brain
#20
Wei-Zhong Zhao, Hsiang-Tsui Wang, Hui-Ju Huang, Yu-Li Lo, Anya Maan-Yuh Lin
Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation...
September 2, 2017: Molecular Neurobiology
keyword
keyword
77545
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"