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Platelet Proteomics

Sophie Braga-Lagache, Natasha Buchs, Mircea-Ioan Iacovache, Benoit Zuber, Christopher Benjamin Jackson, Manfred Heller
BACKGROUND: Cells of the vascular system release spherical vesicles, called microparticles, in the size range of 0.1-1μm induced by a variety of stress factors resulting in variable concentrations between health and disease. Furthermore, microparticles have intercellular communication/signaling properties and interfere with inflammation and coagulation pathways. Today's most used analytical technology for mecroparticle characterization, flow cytometry, is lacking sensitivity and specificity, which might have led to the publication of contradicting results in the past...
October 12, 2016: Molecular & Cellular Proteomics: MCP
Irene Izquierdo, Ángel García
Unwanted platelet activation is associated with numerous diseases, mainly thrombosis-related. In this context, proteomics has emerged as a novel tool with potential for drug target discovery and to scrutinize the effects of antiplatelet drugs. Areas covered: The present review presents the main findings of platelet proteomic studies to date in the context of drug target discovery and perspectives for the future ahead. It includes data and evidences obtained from literature searches on PubMed as well as commentaries derived from the authors' experience and opinions...
October 8, 2016: Expert Review of Proteomics
Clive Metcalfe, Anjana Ramasubramoni, Giordano Pula, Matthew T Harper, Stuart J Mundell, Carmen H Coxon
Thioredoxin (Trx) is an oxidoreductase with important physiological function. Imbalances in the NADPH/thioredoxin reductase/thioredoxin system are associated with a number of pathologies, particularly cancer, and a number of clinical trials for thioredoxin and thioredoxin reductase inhibitors have been carried out or are underway. Due to the emerging role and importance of oxidoreductases for haemostasis and the current interest in developing inhibitors for clinical use, we thought it pertinent to assess whether inhibition of the NADPH/thioredoxin reductase/thioredoxin system affects platelet function and thrombosis...
2016: PloS One
Jidong Chen, Xiaolei Cui, Zhengjiang Qian, Yanjiao Li, Kang Kang, Junle Qu, Li Li, Deming Gou
BACKGROUND: Pulmonary arterial hypertension (PAH) is a lethal disease with pronounced narrowing of pulmonary vessels due to abnormal cell proliferation. The platelet-derived growth factor BB (PDGF-BB) is well known as a potent mitogen for smooth muscle cell proliferation. To better understand how this growth factor regulates pulmonary arterial smooth muscle cells (PASMCs) proliferation, we sought to characterize the response to PDGF-BB stimulation at system-wide levels, including the transcriptome and proteome...
October 6, 2016: BMC Genomics
Clementina Mesaros, Ian A Blair
Mass spectrometry-based proteomics methodology has become an important tool in elucidating some of the underlying mechanisms involved in cardiovascular disease. The present review provides details on selected important protein targets where highly selective and specific mass spectrometry-based approaches have led to important new findings and provided new mechanistic information. The role of six proteins involved in the etiology of cardiovascular disease (acetylated platelet cyclooxygenase-1, serum apolipoprotein A1, apolipoprotein C-III, serum C-reactive protein, serum high mobility group box-1 protein, insulin-like growth factor I) and their quantification has been discussed...
2016: Clinical Proteomics
Maria Kaisar, Leon F A van Dullemen, Marie-Laëtitia Thézénas, M Zeeshan Akhtar, Honglei Huang, Sandrine Rendel, Philip D Charles, Roman Fischer, Rutger J Ploeg, Benedikt M Kessler
BACKGROUND: The successful application of-omics technologies in the discovery of novel biomarkers and targets of therapeutic interventions is facilitated by large collections of well curated clinical samples stored in bio banks. Mining the plasma proteome holds promise to improve our understanding of disease mechanisms and may represent a source of biomarkers. However, a major confounding factor for defining disease-specific proteomic signatures in plasma is the variation in handling and processing of clinical samples leading to protein degradation...
2016: Clinical Proteomics
Tadashi Kondo
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Gain-of-function mutations in KIT or platelet-derived growth factor receptor alpha (PDGFRA) drive most GISTs, and 85 % of GISTs also contain oncogenic mutations in one of two receptor tyrosine kinases. The advent of tyrosine kinase inhibitors has had a significant impact on the clinical practices for GISTs. However, tumors in more than 80 % of GIST patients acquire resistance against treatments with tyrosine kinase inhibitors; thus, driver mechanisms of secondary resistance as well as biomarkers for early detection of recurrence have been explored for better clinical outcomes...
2016: Advances in Experimental Medicine and Biology
F Ciregia, L Kollipara, L Giusti, R P Zahedi, C Giacomelli, M R Mazzoni, G Giannaccini, P Scarpellini, A Urbani, A Sickmann, A Lucacchini, L Bazzichi
Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by unexplained fatigue not improved by rest. An area of investigation is the likely connection of CFS with defective mitochondrial function. In a previous work, we investigated the proteomic salivary profile in a couple of monozygotic twins discordant for CFS. Following this work, we analyzed mitochondrial proteins in the same couple of twins. Nano-liquid chromatography electrospray ionization mass spectrometry (nano-LC-MS) was used to study the mitochondria extracted from platelets of the twins...
September 27, 2016: Translational Psychiatry
Benjarat Phattanawiboon, Narissara Jariyapan, Chonlada Mano, Sittiruk Roytrakul, Atchara Paemanee, Sriwatapron Sor-Suwan, Patchara Sriwichai, Atiporn Saeung, Paul A Bates
Understanding changes in mosquito salivary proteins during the time that sporozoite maturation occurs and after blood feeding may give information regarding the roles of salivary proteins during the malarial transmission. Anopheles dissidens (formerly Anopheles barbirostris species A1) is a potential vector of Plasmodium vivax in Thailand. In this study, analyses of the proteomic profiles of female An. dissidens salivary glands during adult development and after blood feeding were carried out using two-dimensional gel electrophoresis coupled with nano-liquid chromatography-mass spectrometry...
2016: PloS One
Edurne Nuin, Dolores Pérez-Sala, Virginie Lhiaubet-Vallet, Inmaculada Andreu, Miguel A Miranda
Triflusal is a platelet aggregation inhibitor chemically related to acetylsalicylic acid, which is used for the prevention and/or treatment of vascular thromboembolisms, which acts as a prodrug. Actually, after oral administration it is absorbed primarily in the small intestine, binds to plasma proteins (99%) and is rapidly biotransformed in the liver into its deacetylated active metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). In healthy humans, the half-life of triflusal is ca. 0.5 h, whereas for HTB it is ca...
2016: Frontiers in Pharmacology
Ritu Rawal, Sonam Vijay, Kavita Kadian, Jagbir Singh, Veena Pande, Arun Sharma
In order to understand the importance of functional proteins in mosquito behavior, following blood meal, a baseline proteomic dataset is essential for providing insights into the physiology of blood feeding. Therefore, in this study as first step, in solution and 1-D electrophoresis digestion approach combined with tandem mass spectrometry (nano LC-MS/MS) and computational bioinformatics for data mining was used to prepare a baseline proteomic catalogue of salivary gland proteins of sugar fed An. culicifacies mosquitoes...
2016: PloS One
Hangyeore Lee, Sehyun Chae, Jisook Park, Jingi Bae, Eun-Bi Go, Su-Jin Kim, Hokeun Kim, Daehee Hwang, Sang-Won Lee, Soo-Youn Lee
Sarpogrelate is an antiplatelet agent widely used to treat arterial occlusive diseases. Evaluation of platelet aggregation is essential to monitor therapeutic effects of sarpogrelate. Currently, no molecular signatures are available to evaluate platelet aggregation. Here, we performed comprehensive proteome profiling of platelets collected from 14 subjects before and after sarpogrelate administration using LC-MS/MS analysis coupled with extensive fractionation. Of 5,423 proteins detected, we identified 499 proteins affected by sarpogrelate and found that they strongly represented cellular processes related to platelet activation and aggregation, including cell activation, coagulation, and vesicle-mediated transports...
September 6, 2016: Molecular & Cellular Proteomics: MCP
Aneta Wrzyszcz, Joanna Urbaniak, Agnieszka Sapa, Mieczysław Woźniak
To date, there has been no ideal method for blood platelet isolation which allows one to obtain a preparation devoid of contaminations, reflecting the activation status and morphological features of circulating platelets. To address these requirements, we have developed a method which combines the continuous density gradient centrifugation with washing from PGI2-supplemented platelet-rich plasma (PRP). We have assessed the degree of erythrocyte and leukocyte contamination, recovery of platelets, morphological features, activation status, and reactivity of isolated platelets...
September 2, 2016: Platelets
Vahideh Rabani, Damien Montange, Siamak Davani
Lipid-rafts are defined as membrane microdomains enriched in cholesterol and glycosphingolipids within platelet plasma membrane. Lipid raft-mediated clot retraction requires factor XIII and other interacting proteins. The aim of this study was to investigate the proteins that interact with factor XIII in raft and non-raft domains of activated and non-activated platelet plasma membrane. By lipidomics analysis, we identified cholesterol- and sphingomyelin-enriched areas as lipid rafts. Platelets were activated by thrombin...
September 2016: Platelets
Fiorella A Solari, Nadine J A Mattheij, Julia M Burkhart, Frauke Swieringa, Peter W Collins, Judith M E M Cosemans, Albert Sickmann, Johan W M Heemskerk, René P Zahedi
The Scott syndrome is a very rare and likely underdiagnosed bleeding disorder associated with mutations in the gene encoding anoctamin-6. Platelets from Scott patients are impaired in various Ca(2+)-dependent responses, including phosphatidylserine exposure, integrin closure, intracellular protein cleavage, and cytoskeleton-dependent morphological changes. Given the central role of anoctamin-6 in the platelet procoagulant response, we used quantitative proteomics to understand the underlying molecular mechanisms and the complex phenotypic changes in Scott platelets compared with control platelets...
October 2016: Molecular & Cellular Proteomics: MCP
Souad Rahmouni, Alexandre Hego, Céline Delierneux, Odile Wéra, Lucia Musumeci, Lutz Tautz, Cécile Oury
Platelets are small blood cells derived from cytoplasmic fragments of megakaryocytes and play an essential role in thrombosis and hemostasis. Platelet activation depends on the rapid phosphorylation and dephosphorylation of key signaling molecules, and a number of kinases and phosphatases have been identified as major regulators of platelet function. However, the investigation of novel signaling proteins has suffered from technical limitations due to the anucleate nature of platelets and their very limited levels of mRNA and de novo protein synthesis...
2016: Methods in Molecular Biology
Julian Kamhieh-Milz, Shakhawan A Mustafa, Viktor Sterzer, Hatice Celik, Sahime Keski, Omid Khorramshahi, Kamran Movassaghi, Jörg D Hoheisel, Mohamed S S Alhamdani, Abdulgabar Salama
: Platelet storage lesions (PSLs) occur during platelet concentrate (PC) storage. Adverse transfusion reactions (ATRs) have been demonstrated to be more frequent in older PCs and removal of the supernatant prior to transfusion reduces their occurrence. Proteomic profiling of PC supernatants was thus performed to identify proteins associated with PSLs and ATRs. Twenty-four PCs were investigated daily from day 0 to day 9 for platelet pre-activation (PPA), platelet-derived extracellular vesicles (PEVs), and platelet function...
July 28, 2016: Journal of Proteomics
Franziska Mußbach, Hendrik Ungefroren, Bernd Günther, Kathrin Katenkamp, Petra Henklein, Martin Westermann, Utz Settmacher, Lennart Lenk, Susanne Sebens, Jörg P Müller, Frank-Dietmar Böhmer, Roland Kaufmann
BACKGROUND: Previous studies have established that proteinase-activated receptor 2 (PAR2) promotes migration and invasion of hepatocellular carcinoma (HCC) cells, suggesting a role in HCC progression. Here, we assessed the impact of PAR2 in HCC stromal cells on HCC growth using LX-2 hepatic stellate cells (HSCs) and Hep3B cells as model. METHODS: PAR2 expression and function in LX-2 cells was analysed by RT-PCR, confocal immunofluorescence, electron microscopy, and [Ca(2+)]i measurements, respectively...
2016: Molecular Cancer
Jennifer S Myers, Ariana K von Lersner, Qing-Xiang Amy Sang
Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States...
2016: Journal of Cancer
Ben Wood, Matthew P Padula, Denese C Marks, Lacey Johnson
BACKGROUND: Platelets (PLTs) are currently stored at room temperature (22°C), which limits their shelf life, primarily due to the risk of bacterial growth. Alternatives to room temperature storage include PLT refrigeration (2-6°C), which inhibits bacterial growth, thus potentially allowing an extension of shelf life. Additionally, refrigerated PLTs appear more hemostatically active than conventional PLTs, which may be beneficial in certain clinical situations. However, the mechanisms responsible for this hemostatic function are not well characterized...
October 2016: Transfusion
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