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Protease activated receptor

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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
#1
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/28923481/adam17-is-the-main-sheddase-for-the-generation-of-human-triggering-receptor-expressed-in-myeloid-cells-htrem2-ectodomain-and-cleaves-trem2-after-histidine-157
#2
Dominik Feuerbach, Patrick Schindler, Carmen Barske, Stefanie Joller, Edwige Beng-Louka, Katie A Worringer, Sravya Kommineni, Ajamete Kaykas, Daniel J Ho, Chaoyang Ye, Karl Welzenbach, Gaelle Elain, Laurent Klein, Irena Brzak, Anis K Mir, Christopher J Farady, Reiner Aichholz, Simone Popp, Nathalie George, Ulf Neumann
Triggering receptor expressed in myeloid cells (TREM2) is a member of the immunoglobulin superfamily and is expressed in macrophages, dendritic cells, microglia, and osteoclasts. TREM2 plays a role in phagocytosis, regulates release of cytokine, contributes to microglia maintenance, and its ectodomain is shed from the cell surface. Here, the question was addressed at which position sheddases cleave TREM2 and what are the proteases involved in this process. Using both pharmacological and genetic approaches we report that the main protease contributing to the release of TREM2 ectodomain is ADAM17, (a disintegrin and metalloproteinase domain containing protein, also called TACE, TNFα converting enzyme) while ADAM10 plays a minor role...
September 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28923290/use-of-adult-sensory-panel-to-study-individual-differences-in-the-palatability-of-a-pediatric-hiv-treatment-drug
#3
Julie A Mennella, Phoebe S Mathew, Elizabeth D Lowenthal
PURPOSE: The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra(®) [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients...
September 15, 2017: Clinical Therapeutics
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/28918742/a-new-concept-of-action-of-hemostatic-proteases-on-inflammation-neurotoxicity-and-tissue-regeneration
#5
REVIEW
L R Gorbacheva, E V Kiseleva, I G Savinkova, S M Strukova
Key hemostatic serine proteases such as thrombin and activated protein C (APC) are signaling molecules controlling blood coagulation and inflammation, tissue regeneration, neurodegeneration, and some other processes. By interacting with protease-activated receptors (PARs), these enzymes cleave a receptor exodomain and liberate new amino acid sequence known as a tethered ligand, which then activates the initial receptor and induces multiple signaling pathways and cell responses. Among four PAR family members, APC and thrombin mainly act via PAR1, and they trigger divergent effects...
July 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28915606/proteolytic-cleavages-in-the-extracellular-domain-of-receptor-tyrosine-kinases-by-membrane-associated-serine-proteases
#6
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/28915327/adipose-tissue-in-hiv-infection
#7
John R Koethe
HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28912497/selective-antibody-activation-through-protease-activated-pro-antibodies-that-mask-binding-sites-with-inhibitory-domains
#8
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
#9
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
#10
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/28900243/normothermic-microwave-irradiation-induces-death-of-hl-60-cells-through-heat-independent-apoptosis
#11
Mamiko Asano, Satoshi Tanaka, Minoru Sakaguchi, Hitoshi Matsumura, Takako Yamaguchi, Yoshikazu Fujita, Katsuyoshi Tabuse
Microwaves have been used in various cancer therapies to generate heat and increase tumor cell temperature; however, their use is limited by their side-effects in normal cells and the acquisition of heat resistance. We previously developed a microwave irradiation method that kills cultured cancer cells, including a human promyelomonocytic leukemia (HL-60) cell line, by maintaining a cellular temperature of 37 °C during treatment. In the present study, we investigated the mechanisms underlying HL-60 cell death during this treatment...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28898517/characterization-of-the-functional-activity-of-botulinum-neurotoxin-subtype-b6
#12
Tomoko Kohda, Keiji Nakamura, Koji Hosomi, Yasushi Torii, Shunji Kozaki, Masafumi Mukamoto
Clostridium botulinum produces the highly potent neurotoxin, botulinum neurotoxin (BoNT), which is classified into seven serotypes, A-G, and the subtype classification is confirmed by the diversity of the amino acid sequence among the serotypes. The BoNT from the Osaka05 strain is associated with type B infant botulism and has been divided into BoNT/B subtype B6 (BoNT/B6) by phylogenetic analysis and the antigenicity of its C-terminal heavy chain (HC) domain. However, the molecular basis for its properties, including the potency, is poorly understood...
September 12, 2017: Microbiology and Immunology
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
#13
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/28890882/neutrophils-to-the-roscue-mechanisms-of-nadph-oxidase-activation-and-bacterial-resistance
#14
REVIEW
Giang T Nguyen, Erin R Green, Joan Mecsas
Reactive oxygen species (ROS) generated by NADPH oxidase play an important role in antimicrobial host defense and inflammation. Their deficiency in humans results in recurrent and severe bacterial infections, while their unregulated release leads to pathology from excessive inflammation. The release of high concentrations of ROS aids in clearance of invading bacteria. Localization of ROS release to phagosomes containing pathogens limits tissue damage. Host immune cells, like neutrophils, also known as PMNs, will release large amounts of ROS at the site of infection following the activation of surface receptors...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28889362/a-novel-aza-mbp-altered-peptide-ligand-for-the-treatment-of-experimental-autoimmune-encephalomyelitis
#15
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/28888033/modulation-of-%C3%AE-%C3%AE-t-cell-activation-by-neutrophil-elastase
#16
Nadia Yasmín Towstyka, Carolina Maiumi Shiromizu, Irene Keitelman, Florencia Sabbione, Gabriela Verónica Salamone, Jorge Raúl Geffner, Analía Silvina Trevani, Carolina Cristina Jancic
γδ T cells are non-conventional, innate-like T cells, characterized by a restricted TCR repertoire. They participate in protective immunity response against extracellular and intracellular pathogens, tumor surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance, and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood γδ T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of IFN-γ and TNF-α induced by anti-CD3 antibodies were potentiated by neutrophils...
September 9, 2017: Immunology
https://www.readbyqxmd.com/read/28886438/daidzein-down-regulates-ubiquitin-specific-protease-19-expression-through-estrogen-receptor-%C3%AE-and-increases-skeletal-muscle-mass-in-young-female-mice
#17
Masahiro Ogawa, Takehiro Kitano, Natsuha Kawata, Takashi Sugihira, Tomoya Kitakaze, Naoki Harada, Ryoichi Yamaji
Ubiquitin-specific protease 19 (USP19) is a key player in the negative regulation of muscle mass during muscle atrophy. Loss-of-function approaches demonstrate that 17β-estradiol (E2) increases USP19 expression through estrogen receptor (ER) α and consequently decreases soleus muscle mass in young female mice under physiological conditions. Daidzein is one of the main isoflavones in soy, and activates ERβ-dependent transcription. Here, we investigated the effects of daidzein on E2-increased USP19 expression and E2-decreased soleus muscle mass in young female mice...
August 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28883694/cytoplasmic-domain-of-tissue-factor-promotes-liver-fibrosis-in-mice
#18
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
#19
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/28881486/how-usp18-deals-with-isg15-modified-proteins-structural-basis-for-the-specificity-of-the-protease
#20
REVIEW
Anja Basters, Klaus-Peter Knobeloch, Günter Fritz
The Ubiquitin-specific protease 18 (USP18) has two major functions: (i) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon stimulated gene 15 kDa) from proteins, and (ii) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor...
September 7, 2017: FEBS Journal
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