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Platelet integrin

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https://www.readbyqxmd.com/read/27929375/implications-of-the-differing-roles-of-the-%C3%AE-1-and-%C3%AE-3-transmembrane-and-cytosplasmic-domains-for-integrin-function
#1
Zhenwei Lu, Sijo Mathew, Jiang Chen, Arina Hadziselimovic, Riya Palamuttam, Billy G Hudson, Reinhard Faessler, Ambra Pozzi, Charles R Sanders, Roy Zent
Integrins are transmembrane receptors composed of α and β subunits. Although most integrins contain β1, canonical activation mechanisms are based on studies of the platelet integrin, αIIbβ3. Its inactive conformation is characterized by association of the αIIb transmembrane and cytosolic domain (TM/CT) with a tilted β3 TM/CT that leads to activation when disrupted. We show significant structural differences between β1 and β3 TM/CT in bicelles. Moreover, the 'snorkeling' lysine at the TM/CT interface of β subunits, previously proposed to regulate αIIbβ3 activation by ion pairing with nearby lipids, plays opposite roles in β1 and β3 integrin function and in neither case is responsible for TM tilt...
December 8, 2016: ELife
https://www.readbyqxmd.com/read/27925685/in-vitro-characterization-of-synthoplate-%C3%A2-synthetic-platelet-technology-and-its-in-vivo-evaluation-in-severely-thrombocytopenic-mice
#2
Meenal Shukla, Ujjal D S Sekhon, Venkaiah Betapudi, Wei Li, DaShawn A Hickman, Christa L Pawlowski, Mitchell R Dyer, Matthew D Neal, Keith R McCrae, Anirban Sen Gupta
BACKGROUND: Platelet transfusion applications face severe challenges due to the limited availability and portability, high risk of contamination and short shelf-life of platelets. Therefore there is significant interest in synthetic platelet substitutes that can render hemostasis while avoiding these issues. Platelets promote hemostasis by injury site-selective adhesion and aggregation, and propagation of coagulation reactions on their membrane. Based on these mechanisms, we have developed a synthetic platelet technology (SynthoPlate(™) ) that integrates platelet-mimetic site-selective 'adhesion' and 'aggregation' functionalities via heteromultivalent surface-decoration of lipid vesicles with Von Willebrand Factor-binding, collagen-binding and active platelet integrin GPIIb-IIIa-binding peptides...
December 7, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27923566/flavonolignans-inhibit-adp-induced-blood-platelets-activation-and-aggregation-in-whole-blood
#3
Michal Bijak, Rafal Szelenberger, Joanna Saluk, Pawel Nowak
Flavonolignans are a group of active chemical compounds presented in the silymarin - a standardized extract obtained from fruits and seeds of Milk thistle (Silybum marianum L. Gaernt.). Since the 70s of the last century, flavonolignans have been regarded to the official medicine as a substances having hepatoprotective properties. However many researches performed in recent years have demonstrated that flavonolignans posses many other healthy properties including modulation of variety cell-signaling pathways...
December 3, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27923225/integrin-%C3%AE-iib%C3%AE-3-dependent-erk-signaling-is-regulated-by-src-and-rho-kinases-in-both-leu33-and-pro33-polymorphic-isoforms
#4
Khon C Huynh, Thi-Hiep Nguyen, Dinh Chuong Pham, Huong T T Nguyen, Toi Van Vo, Marianna Gyenes, Volker R Stoldt
Platelet integrin αIIbβ3 possesses a Leu/Pro polymorphism at residue 33 (Leu33/HPA-1a or Pro33/HPA-1b). The Pro33 isoform has been suggested to exhibit prothrombotic features. αIIbβ3-expressing CHO (Chinese hamster ovary) cells on immobilized fibrinogen show activation of the MAP kinase family member ERK2, with an enhanced ERK2 activity in Pro33 cells compared to Leu33 cells. In our present work, we examined how the Leu/Pro polymorphism modulates the ERK2 activation stimulated by 2 differently triggered outside-in signalings...
December 7, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27915054/curdione-attenuates-thrombin-induced-human-platelet-activation-%C3%AE-1-tubulin-as-a-potential-therapeutic-target
#5
Dongling Zhang, Wenhao Qiao, Yingli Zhao, Hui Fang, Dujuan Xu, Quan Xia
Rhizoma Curcumae, the dry rhizomes derived from Curcuma aromatica Salisb., are a classical Chinese medicinal herb used to activate blood circulation, remove blood stasis and alleviate pain. Our previous study proved that curdione, a sesquiterpene compound isolated from the essential oil of Curcuma aromatica Salisb. can inhibit platelet activation suggesting its significant anticoagulant and antithrombotic effects. However, the underlying mechanism of curdione mediated anti-platelet effect has not been fully elucidated...
November 30, 2016: Fitoterapia
https://www.readbyqxmd.com/read/27914085/determining-platelet-activation-and-aggregation-in-response-to-bacteria
#6
Oonagh Shannon
Many pathogenic bacteria have been reported to interact with human platelets to mediate platelet activation and aggregation. The importance of these interactions to the immune response or pathogenesis of bacterial infection has not been clarified. It may therefore be valuable to assess platelet responses mediated by diverse strains of bacteria. Here, I describe a method to study platelet integrin activation and granule release using flow cytometry, and a complementary method to study platelet aggregation using a dedicated platelet aggregometer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27909290/highly-sensitive-detection-of-minimal-cardiac-ischemia-using-positron-emission-tomography-imaging-of-activated-platelets
#7
Melanie Ziegler, Karen Alt, Brett M Paterson, Peter Kanellakis, Alex Bobik, Paul S Donnelly, Christoph E Hagemeyer, Karlheinz Peter
A reliable method for the diagnosis of minimal cardiac ischemia would meet a strong demand for the sensitive diagnosis of coronary artery disease in cardiac stress testing and risk stratification in patients with chest pain but unremarkable ECGs and biomarkers. We hypothesized that platelets accumulate early on in ischemic myocardium and a newly developed technology of non-invasive molecular PET imaging of activated platelets can thus detect minimal degrees of myocardial ischemia. To induce different degrees of minimal cardiac ischemia, the left anterior descending artery (LAD) was ligated for 10, 20 or 60 min...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903653/the-phosphatidylinositol-3-4-5-trisphosphate-pi-3-4-5-p3-binder-rasa3-regulates-phosphoinositide-3-kinase-pi-3-kinase-dependent-integrin-%C3%AE-iib%C3%AE-3-outside-in-signaling
#8
Anthony M Battram, Tom N Durrant, Ejaife O Agbani, Kate J Heesom, David S Paul, Raymond Piatt, Alastair W Poole, Peter J Cullen, Wolfgang Bergmeier, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI 3-kinase) family of lipid kinases plays an important role in integrin αIIbβ3 function, thereby supporting thrombus growth and consolidation. Here, we identify the Ras/Rap1GAP Rasa3 (GAP1IP4BP) as a major phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3)-binding protein in human platelets and a key regulator of integrin αIIbβ3 outside-in signaling. We demonstrate that cytosolic Rasa3 translocates to the plasma membrane in a PI 3kinase-dependent manner upon activation of human platelets...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signalling-and-platelet-function-through-upregulation-of-protein-kinase-a-activity
#9
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
BACKGROUND: Agonists for the peroxisome proliferator activated receptor PPARγ, have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists. OBJECTIVES: Profound effects on thrombus formation led us to suspect a role for PPARγ agonists in the regulation of integrin αIIbβ3 mediated signalling. Both GPVI and GPCR signalling pathways lead to αIIbβ3 activation, and signalling through αIIbβ3 plays a critical role in platelet function and normal haemostasis...
November 29, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27895638/intercellular-interactions-as-regulators-of-netosis
#10
REVIEW
Nayef M Kazzaz, Gautam Sule, Jason S Knight
Neutrophil extracellular traps (NETs) are chromatin-derived webs extruded from neutrophils in response to either infection or sterile stimulation with chemicals, cytokines, or microbial products. The vast majority of studies have characterized NET release (also called NETosis) in pure neutrophil cultures in vitro. The situation is surely more complex in vivo as neutrophils constantly sample not only pathogens and soluble mediators but also signals from cellular partners, including platelets and endothelial cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27889386/protein-disulfide-isomerases-redox-connections-in-and-out-of-the-endoplasmic-reticulum
#11
Ana Iochabel Soares Moretti, Francisco Rafael Martins Laurindo
Protein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent...
November 24, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27860426/human-corneal-fibroblast-migration-and-ecm-synthesis-during-stromal-repair-role-played-by-pdgf-bb-bfgf-and-tgf%C3%AE-1
#12
Patricia Gallego-Muñoz, Lucía Ibares-Frías, José A Garrote, María Cruz Valsero-Blanco, Roberto Cantalapiedra-Rodríguez, Jesús Merayo-Lloves, M Carmen Martínez-García
The development of treatments that modulate corneal wound healing to avoid fibrosis during tissue repair is important for the restoration of corneal transparency after an injury. To date, few studies have studied the influence of growth factors (GFs) on human corneal fibroblast (HCF) expression of extracellular matrix (ECM) proteins such as collagen types I and III, proteoglycans such as perlecan, or proteins implicated in cellular migration such as α5β1-integrin and syndecan-4. Using in vitro HCFs, we developed a mechanical wound model to study the influence of the GFs basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF-BB), and transforming growth factor beta 1 (TGFβ1) on ECM protein production and cellular migration...
November 15, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27851790/functional-effect-of-the-mutations-similar-to-the-cleavage-during-platelet-activation-at-integrin-%C3%AE-3-cytoplasmic-tail-when-expressed-in-mouse-platelets
#13
Xiaofeng Shi, Jichun Yang, Xiongying Cui, Jiansong Huang, Zhangbiao Long, Yulan Zhou, Ping Liu, Lanlan Tao, Zheng Ruan, Bing Xiao, Wei Zhang, Dongya Li, Kesheng Dai, Jianhua Mao, Xiaodong Xi
Previous studies in Chinese hamster ovary cells showed that truncational mutations of β3 at sites of F754 and Y759 mimicking calpain cleavage regulate integrin signaling. The roles of the sequence from F754 to C-terminus and the conservative N756ITY759 motif in platelet function have yet to be elaborated. Mice expressing β3 with F754 and Y759 truncations, or NITY deletion (β3-ΔTNITYRGT, β3-ΔRGT, or β3-ΔNITY) were established through transplanting the homozygous β3-deficient mouse bone marrow cells infected by the GFP tagged MSCV MigR1 retroviral vector encoding different β3 mutants into lethally radiated wild-type mice...
2016: PloS One
https://www.readbyqxmd.com/read/27848264/underlying-mechanism-and-specific-prevention-of-hemolysis-induced-platelet-activation
#14
Thomas Gremmel, Simone Fedrizzi, Günter Weigel, Beate Eichelberger, Simon Panzer
Thromboembolic complications significantly impair the outcome of hemolytic disorders. We hypothesized that red cell adenosine diphosphate (ADP) release results in significant platelet activation in hemolysis and that this prothrombotic state can be prevented by inhibition of the ADP P2Y12 receptor. In the current study, we therefore sought to investigate the mechanism and inhibition of hemolysis-induced platelet activation. The expression of activated integrin αIIbß3 was determined by flow cytometry, and platelet aggregation was assessed by multiple electrode platelet aggregometry...
November 16, 2016: Platelets
https://www.readbyqxmd.com/read/27829061/rgs10-negatively-regulates-platelet-activation-and-thrombogenesis
#15
Nicole R Hensch, Zubair A Karim, Kirk M Druey, Malú G Tansey, Fadi T Khasawneh
Regulators of G protein signaling (RGS) proteins act as GTPase activating proteins to negatively regulate G protein-coupled receptor (GPCR) signaling. Although several RGS proteins including RGS2, RGS16, RGS10, and RGS18 are expressed in human and mouse platelets, the respective unique function(s) of each have not been fully delineated. RGS10 is a member of the D/R12 subfamily of RGS proteins and is expressed in microglia, macrophages, megakaryocytes, and platelets. We used a genetic approach to examine the role(s) of RGS10 in platelet activation in vitro and hemostasis and thrombosis in vivo...
2016: PloS One
https://www.readbyqxmd.com/read/27827357/platelet-integrin-%C3%AE-iib%C3%AE-3-inhibitor-rescues-progression-of-apoptosis-in-human-platelets
#16
Jie Zhu, Qinghang Wang, Yumei Nie, Rong Yan, Kesheng Dai, Birong Zhou
BACKGROUND Apoptosis plays an important role in the physiology of platelet function. We aimed to detect the effect of the platelet integrin αIIbβ3 inhibitor, tirofiban, on apoptotic events, including mitochondrial inner-membrane potential (ΔΨm), phosphatidylserine (PS) exposure on platelet surface, and the generation of reactive oxygen species (ROS), when washed platelets were stimulated with thrombin. MATERIAL AND METHODS The study included washed platelets from healthy humans, divided into 4 groups: vehicle, and tirofiban (0...
November 9, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27824126/preservation-of-epithelial-progenitor-cells-from-collagenase-digested-oral-mucosa-during-ex-vivo-cultivation
#17
Yi-Jen Hsueh, Shiang-Fu Huang, Jui-Yang Lai, Shih-Chieh Ma, Hung-Chi Chen, Sung-En Wu, Tze-Kai Wang, Chi-Chin Sun, Kevin Sheng-Kai Ma, Jan-Kan Chen, Chyong-Huey Lai, David Hui-Kang Ma
To avoid xenogeneic infection, we report a novel protocol for producing animal-derived component-free oral mucosal epithelial cells (OMECs) sheet for transplantation, in which collagenase was used to replace dispase II/trypsin-EDTA for digesting oral mucosal tissue, and human platelet-derived PLTMax to replace fetal bovine serum. The resulting epithelial aggregates were expanded on de-epithelialized amniotic membranes without 3T3 feeder cells, and serum-free EpiLife was used to reduce contamination by submucosal mesenchymal cells...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27803165/galpha13-switch-region-2-relieves-talin-autoinhibition-to-activate-alphaiibbeta3-integrin
#18
James Schiemer, Andrew Bohm, Li Lin, Glenn Merrill-Skoloff, Robert Flaumenhaft, Jin-Sheng Huang, Guy C Le Breton, Athar H Chishti
Integrins function as bi-directional signaling transducers that regulate cell-cell and cell-matrix signals across the membrane. A key modulator of integrin activation is talin, a large cytoskeletal protein that exists in an autoinhibited state in quiescent cells. Talin is a large 235 kDa protein comprised of an N-terminal 45 kDa FERM domain, also known as the talin head domain (THD), and a series of helical bundles known as the rod domain. The talin head domain consists of 4 distinct lobes designated as F0-F3...
November 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27802906/platelet-mediated-modulation-of-adaptive-immunity
#19
REVIEW
Matteo Iannacone
Besides being the main cellular effectors of hemostasis, platelets possess a plethora of intracellular mediators (e.g. cytokines, chemokines and antimicrobial molecules) as well as surface receptors (e.g. P-selectin, integrins, CD40L, intercellular adhesion molecule [ICAM]-2, junctional adhesion molecule [JAM]-A, CD44, Toll-like receptors, chemokine receptors) known for their involvement in inflammatory and immune responses. These aspects of platelet biology, which suggest an evolutionary link to a more primitive multifunctional innate defensive cell, position platelets at the interface between coagulation and immunity...
October 29, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27796783/structural-and-functional-aspects-of-decorsin-and-its-analog-as-recognized-by-integrin-%C3%AE-iib%C3%AE-3
#20
Xingzhen Lao, Jingxiao Bao, Tingting Yu, Qingqing Li, Heng Zheng
Decorsin is an antagonist of platelet glycoprotein integrin αIIbβ3 on platelets; the protein is 39 amino acids long with three disulfide bridges in its tertiary structure. To demonstrate decorsin's mechanism of action, we applied the computational virtual technique and platelet aggregation inhibition assay, which showed that the flanking amino-acid residues of the Arg-Gly-Asp (RGD) motif play an important role in platelet aggregation. The computational simulations revealed that the RGD motif mainly contributes to the stability of the complex when decorsion interacts with integrin αIIbβ3...
November 2016: Journal of Molecular Modeling
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