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Platelet integrin

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https://www.readbyqxmd.com/read/28214869/effects-of-antimalarial-tafenoquine-on-blood-platelet-activity-and-survival
#1
Hang Cao, Rosi Bissinger, Anja T Umbach, Abdulla Al Mamun Bhuyan, Florian Lang, Meinrad Gawaz
BACKGROUND/AIMS: The 8-aminoquinoline tafenoquine has been shown to be effective against Plasmodia, Leishmania and Trypanosoma. The substance is at least in part effective by triggering apoptosis of the parasites. Moreover, tafenoquine has been shown to trigger eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. The effect of tafenoquine on eryptosis is in part due to stimulation of Ca2+ entry and oxidative stress...
January 26, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28195700/discovery-and-characterization-of-a-potent-and-specific-peptide-ligand-targeting-endothelial-progenitor-cells-and-endothelial-cells-for-tissue-regeneration
#2
Dake Hao, Wenwu Xiao, Ruiwu Liu, Priyadarsini Kumar, YuanPei Li, Ping Zhou, Fuzheng Guo, Diana L Farmer, Kit S Lam, Fengshan Wang, Aijun Wang
Endothelial progenitor cells (EPCs) and endothelial cells (ECs) play a vital role in endothelialization and vascularization for tissue regeneration. Various EPC/EC targeting biomolecules have been investigated to improve tissue regeneration with limited success often due to their limited functional specificity and structural stability. One-Bead-One-Compound (OBOC) combinatorial technology is an ultra-high throughput chemical library synthesis and screening method suitable for ligand discovery against a wide range of biological targets, such as integrins...
February 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28194217/schisandra-chinensis-and-morus-alba-synergistically-inhibit-in-vivo-thrombus-formation-and-platelet-aggregation-by-impairing-the-glycoprotein-vi-pathway
#3
Dong-Seon Kim, Muhammad Irfan, Yoon-Young Sung, Seung Hyung Kim, Sun Haeng Park, Young Hyun Choi, Man Hee Rhee, Ho Kyoung Kim
Morus alba L. (MAL) extract has been used in traditional medicine for its cardioprotective and antiplatelet effects, while another herbal remedy, Schisandra chinensis (SCC), has been reported to have anti-inflammatory and antioxidant properties. We evaluated underlying cellular changes exerted by extracts of these plants on platelet function and effects of SCC + MAL on in vivo thrombus formation using AV shunt and tail thrombosis-length models in rats. In vitro platelet aggregation, granule secretion, and [Ca(2+)] i release assays were carried out...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28192121/convulxin-a-c-type-lectin-like-protein-inhibits-hcasmcs-functions-via-wad-motif-integrin-%C3%AE-v-interaction-and-nf-%C3%AE%C2%BAb-independent-gene-suppression-of-gro-and-il-8
#4
Chun-Ho Shih, Tin-Bin Chiang, Wen-Jeng Wang
Convulxin (CVX), a C-type lectin-like protein (CLPs), is a potent platelet aggregation inducer. To evaluate its potential applications in angiogenic diseases, the multimeric CVX were further explored on its mode of actions toward human coronary artery smooth muscle cells (HCASMCs). The N-terminus of β-chain of CVX (CVX-β) contains a putative disintegrin-like domain with a conserved motif upon the sequence comparison with other CLPs. Importantly, native CVX had no cytotoxic activity as examined by electrophoretic pattern...
February 10, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28174163/platelets-and-von-willebrand-factor-in-atherogenesis
#5
Melinda D Wu, Tamara M Atkinson, Jonathan R Lindner
The role of platelet adhesion, activation and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well-established. There is increasing evidence that platelet-endothelial interactions also contribute to early atherosclerotic plaque initiation and growth. Through these interactions, platelet-derived factors can contribute to the pro-inflammatory and mitogenic status of resident mural cells. Among the many putative mechanisms for platelet-endothelial interactions, increased endothelial-associated Von Willebrand factor, particularly in a multimerized form, which interacts with platelet GPIbα and integrins is a major factor, and represents a therapeutic target for early atherogenesis...
February 7, 2017: Blood
https://www.readbyqxmd.com/read/28166238/integrin-dependent-cell-adhesion-to-neutrophil-extracellular-traps-through-engagement-of-fibronectin-in-neutrophil-like-cells
#6
Marcello Monti, Francesca Iommelli, Viviana De Rosa, Maria Vincenza Carriero, Roberta Miceli, Rosa Camerlingo, Giovanni Di Minno, Silvana Del Vecchio
Neutrophil extracellular traps (NETs), originally recognized as a host defense mechanism, were reported to promote thrombosis and metastatic dissemination of cancer cells. Here we tested the role of integrins α5β1 and ανβ3 in the adhesion of cancer cells to NETs. Neutrophil-like cells stimulated with calcium ionophore (A23187) were used as a stable source of cell-free NETs-enriched suspensions. Using NETs as an adhesion substrate, two human K562 cell lines, differentially expressing α5β1 and ανβ3 integrins, were subjected to adhesion assays in the presence or absence of DNAse 1, blocking antibodies against α5β1 or ανβ3, alone or in combination with DNAse 1, and Proteinase K...
2017: PloS One
https://www.readbyqxmd.com/read/28160743/dioxolanea3-phosphatidylethanolamines-are-generated-by-human-platelets-and-stimulate-neutrophil-integrin-expression
#7
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/28155614/cartilage-oligomeric-matrix-protein-matricellular-and-matricrine-signaling-in-cardiovascular-homeostasis-and-disease
#8
Yi Fu, Wei Kong
Cardiovascular (CV) diseases remain a leading cause of morbidity and mortality in the world. Increasing the understanding of the pathogenesis of various CV diseases may provide novel therapeutic targets to improve their prevention and treatment. Cartilage oligomeric matrix protein (COMP), also known as thrombospondin-5 (TSP-5), is a matricellular protein that is abundantly expressed in both cartilage and the CV system. Our group and others have identified COMP as playing critical roles in maintaining CV homeostasis...
February 1, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28148841/platelet-localized-fxi-promotes-a-vascular-coagulation-inflammatory-circuit-in-arterial-hypertension
#9
Sabine Kossmann, Jeremy Lagrange, Sven Jäckel, Kerstin Jurk, Moritz Ehlken, Tanja Schönfelder, Yvonne Weihert, Maike Knorr, Moritz Brandt, Ning Xia, Huige Li, Andreas Daiber, Matthias Oelze, Christoph Reinhardt, Karl Lackner, Andras Gruber, Brett Monia, Susanne H Karbach, Ulrich Walter, Zaverio M Ruggeri, Thomas Renné, Wolfram Ruf, Thomas Münzel, Philip Wenzel
Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function...
February 1, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28136130/integrin-%C3%AE-8-is-abundant-in-human-rat-and-mouse-trophoblasts
#10
Sebastian Herdl, Hanna Huebner, Gudrun Volkert, Ines Marek, Carlos Menendez-Castro, Stephanie C Noegel, Matthias Ruebner, Wolfgang Rascher, Andrea Hartner, Fabian B Fahlbusch
OBJECTIVE: Integrins exert regulatory functions in placentogenesis. Null mutation of certain integrin α subunits leads to placental defects with subsequent fetal growth restriction or embryonic lethality in mice. So far, the placental role of α8 integrin remains to be determined. METHODS: Localization of α8 integrin and its ligands, fibronectin (FN) and osteopontin (OPN), was studied by immunohistochemistry in human, rat, and mouse placenta. The vascularization of the placental labyrinth layer of α8 integrin-deficient mice was determined by CD31 staining...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28123327/the-inhibitory-activity-of-ginsenoside-rp4-in-adenosine-diphosphate-induced-platelet-aggregation
#11
Young-Min Son, Da-Hye Jeong, Hwa-Jin Park, Man-Hee Rhee
BACKGROUND: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification...
January 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28122739/integrin-psi-domain-has-endogenous-thiol-isomerase-function-and-is-a-novel-target-for-anti-platelet-therapy
#12
Guangheng Zhu, Qing Zhang, Emily C Reddy, Naadiya Carrim, Yunfeng Chen, Xiaohong Ruby Xu, Miao Xu, Yiming Wang, Yan Hou, Li Ma, Yan Li, Min Rui, Tania Petruzziello, Christopher Lavalle, Tyler W Stratton, Xi Lei, Adili Reheman, Pingguo Chen, Cheng Zhu, John A Wilkins, Richard O Hynes, John Freedman, Heyu Ni
Integrins are a large family of heterodimeric transmembrane receptors differentially expressed on almost all metazoan cells. Integrin β subunits contain a highly conserved plexin-semaphorin-integrin (PSI) domain. The CXXC motif, the active site of protein-disulfide-isomerase (PDI) family, is expressed twice in this domain of all integrins across species. However, the role of PSI domain in integrins and whether it contains thiol-isomerase activity have not been explored. Here, recombinant PSI domains of murine β3, human β1 and β2 integrins were generated and their PDI-like activity was demonstrated by refolding of reduced/denatured RNase...
January 25, 2017: Blood
https://www.readbyqxmd.com/read/28115185/plasma-kallikrein-enhances-platelet-aggregation-response-by-subthreshold-doses-of-adp
#13
Tatiana F Ottaiano, Sheila S Andrade, Cleide de Oliveira, Mariana C C Silva, Marcus V Buri, Maria A Juliano, Manoel J B C Girão, Misako U Sampaio, Alvin H Schmaier, Alexander Wlodawer, Francisco H A Maffei, Maria L V Oliva
Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin αIIbβ3 through interactions with the KGD/KGE sequence motif in huPK. Integrin αIIbβ3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway...
January 20, 2017: Biochimie
https://www.readbyqxmd.com/read/28109047/novel-antiplatelet-role-for-a-protein-disulfide-isomerase-targeted-peptide-evidence-of-covalent-binding-to-c-terminal-cghc-redox-motif
#14
H R Sousa, R S Gaspar, E M L Sena, S A da Silva, J L de L Fontelles, T L S Araújo, M Mastrogiovanni, D M Fries, A P S Azevedo-Santos, F R M Laurindo, A Trostchansky, A M Paes
Protein disulfide isomerase (PDI) plays a major role in platelet aggregation and its inhibitors have emerged as novel antithrombotic drugs. In previous work, we designed a peptide based on PDI redox motif (CGHC) that inhibited both PDI reductase activity and PDI-modulated superoxide generation by neutrophil Nox2. Thus, we hypothesized this peptide would also inhibit platelet aggregation by association to surface PDI. Three peptides were used: CxxC, containing the PDI redox motif; Scr, presenting a scrambled sequence of the same residues and AxxA, with cysteines replaced by alanine...
January 21, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28101696/role-of-the-helix-in-talin-f3-domain-f3-helix-in-talin-mediated-integrin-activation
#15
Ang Li, Qiang Guo, Ailin Wei, Yaliang Zhou, Weiming Hu
Increases in ligand binding to cellular integrins (activation) play an important role in platelet and leukocyte function. Talin is necessary in vivo and sufficient in vitro for integrin αIIbβ3 activation. The precise mechanisms by which talin activates integrin are still being elucidated. In particular, talin undergoes conformational changes (around the F3 helix) and inserts the F3 helix into lipid bilayer; however, the connection between this lipid-inserting mechanism of talin and talin's capacity to activate integrin has never been explored before...
January 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28092265/the-fibronectin-synergy-site-re-enforces-cell-adhesion-and-mediates-a-crosstalk-between-integrin-classes
#16
Maria Benito-Jardón, Sarah Klapproth, Irene Gimeno-LLuch, Tobias Petzold, Mitasha Bharadwaj, Daniel J Müller, Gabriele Zuchtriegel, Christoph A Reichel, Mercedes Costell
Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1(syn/syn)) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality...
January 16, 2017: ELife
https://www.readbyqxmd.com/read/28078347/alterations-of-the-platelet-proteome-in-type-i-glanzmann-thrombasthenia-caused-by-different-homozygous-delg-frameshift-mutations-in-itga2b
#17
Stefan Loroch, Katharina Trabold, Stepan Gambaryan, Cora Reiß, Kathrin Schwierczek, Ingrid Fleming, Albert Sickmann, Wolfgang Behnisch, Barbara Zieger, René P Zahedi, Ulrich Walter, Kerstin Jurk
Glanzmann thrombasthenia (GT) is one of the best characterized inherited platelet function disorders but global platelet proteome has not been determined in these patients. We investigated the proteome and function of platelets from two patients with type I GT, caused by different homozygous ITGA2b mutations, from family members and unrelated controls. The global proteome of highly purified washed platelets was quantified by liquid chromatography-mass spectrometry (LC-MS) and targeted MS-methods. Platelet function was analysed by flow cytometry, light transmission aggregometry and flow-based assays...
January 12, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28076805/regulation-of-active-icam-4-on-normal-and-sickle-cell-disease-rbcs-via-akaps-is-revealed-by-afm
#18
Jing Zhang, Krithika Abiraman, Sasia-Marie Jones, George Lykotrafitis, Biree Andemariam
Human healthy (wild-type (WT)) and homozygous sickle (SS) red blood cells (RBCs) express a large number of surface receptors that mediate cell adhesion between RBCs, and between RBCs and white blood cells, platelets, and the endothelium. In sickle cell disease (SCD), abnormal adhesion of RBCs to endothelial cells is mediated by the intercellular adhesion molecule-4 (ICAM-4), which appears on the RBC membrane and binds to the endothelial αvβ3 integrin. This is a key factor in the initiation of vaso-occlusive episodes, the hallmark of SCD...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28060719/temporal-quantitative-phosphoproteomics-of-adp-stimulation-reveals-novel-central-nodes-in-platelet-activation-and-inhibition
#19
Florian Beck, Jörg Geiger, Stepan Gambaryan, Fiorella A Solari, Margherita Dell'Aica, Stefan Loroch, Nadine J Mattheij, Igor Mindukshev, Oliver Pötz, Kerstin Jurk, Julia M Burkhart, Christian Fufezan, Johan W M Heemskerk, Ulrich Walter, René P Zahedi, Albert Sickmann
Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin αIIbβ3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies...
January 12, 2017: Blood
https://www.readbyqxmd.com/read/28058806/clustering-of-glycoprotein%C3%A2-vi-gpvi-dimers-upon-adhesion-to-collagen-as-a-mechanism-to-regulate-gpvi-signaling-in-platelets
#20
N S Poulter, A Y Pollitt, D M Owen, E E Gardiner, R K Andrews, H Shimizu, D Ishikawa, D Bihan, R W Farndale, M Moroi, S P Watson, S M Jung
Essentials Dimeric high-affinity collagen receptor glycoprotein VI (GPVI) is present on resting platelets. Spatio-temporal organization of platelet GPVI-dimers was evaluated using advanced microscopy. Upon platelet adhesion to collagenous substrates, GPVI-dimers coalesce to form clusters. Clustering of GPVI-dimers may increase avidity and facilitate platelet activation SUMMARY: Background Platelet glycoprotein VI (GPVI) binding to subendothelial collagen exposed upon blood vessel injury initiates thrombus formation...
January 6, 2017: Journal of Thrombosis and Haemostasis: JTH
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