Download PDF
Thromb Haemost 2005; 94(05): 916-925
DOI: 10.1160/TH05-02-0121
Review Article
Schattauer GmbH

Understanding platelets

Lessons from proteomics, genomics and promises from network analysis
Marcus Dittrich
1   Department of Bioinformatics, Biocenter
2   Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
,
Ingvild Birschmann
2   Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
,
Christiane Stuhlfelder
3   Rudolf Virchow-Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
,
Albert Sickmann
3   Rudolf Virchow-Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
,
Sabine Herterich
2   Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
,
Bernhard Nieswandt
2   Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
3   Rudolf Virchow-Center for Experimental Biomedicine, University of Würzburg, Würzburg, Germany
,
Ulrich Walter
2   Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany
,
Thomas Dandekar
1   Department of Bioinformatics, Biocenter
4   EMBL, Heidelberg, Germany
› Author Affiliations Financial support: The original research of the authors is supported by the Deutsche Forschungsgemeinschaft.
Further Information

Publication History

Received: 20 February 2005

Accepted after resubmission: 03 August 2005

Publication Date:
14 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

New large-scale analysis techniques such as bioinformatics, mass spectrometry and SAGE data analysis will allow a new framework for understanding platelets. This review analyses some important options and tasks for these tools and examines an outline of the new, refined picture of the platelet outlined by these new techniques. Looking at the platelet-specific building blocks of genome, (active) transcriptome and proteome (notably secretome and phospho-proteome), we summarize current bioinformatical and biochemical approaches, tasks as well as their limitations. Understanding the surprisingly complex platelet regarding compartmentalization, key cascades, and pathways including clinical implications will remain an exciting and hopefully fruitful challenge for the future.

Keywords

Pathway - mass spectrometry - transcriptome - platelet - post-transcriptional - coagulation - hemostasis
 

  • References

  • 1 Weyrich AS, Zimmerman GA. Evaluating the relevance of the platelet transcriptome. Blood 2003; 102: 1550-1.
    CrossrefPubMedGoogle Scholar
  • 2 Levin J. The evolution of mammalian platelets. Platelets.. Academic Press; 2002: 3-19.
    Google Scholar
  • 3 Cooper EL, Kauschke E, Cossarizza A. Digging for innate immunity since Darwin and Metchnikoff. Bioessays 2002; 24: 319-33.
    CrossrefPubMedGoogle Scholar
  • 4 Rothenberg E, Davidson E. Regulatory co-options in the evolution of deuterostome immune systems. Innate Immunity. 2003; 61-87.
    PubMedGoogle Scholar
  • 5 Royet J, Meister M, Ferrandon D. Humoral and cellular responses in Drosophilia. Innate Immunity. 2003; 137-53.
    PubMedGoogle Scholar
  • 6 Reed G. Platelet Secretion. Platelets.. Academic Press; 2002: 181-95.
    Google Scholar
  • 7 Maguire PB, Moran N, Cagney G. et al. Application of proteomics to the study of platelet regulatory mechanisms. Trends Cardiovasc Med 2004; 14: 207-20.
    CrossrefPubMedGoogle Scholar
  • 8 Garcia A, Watson SP, Dwek RA. et al. Applying proteomics technology to platelet research. Mass Spectrom Rev. 2004
    PubMedGoogle Scholar
  • 9 Booyse F, Rafelson Jr. ME. In vitro incorporation of amino-acids into the contractile protein of human blood platelets. Nature 1967; 215: 283-4.
    CrossrefPubMedGoogle Scholar
  • 10 Booyse FM, Rafelson Jr. ME. Studies on human platelets. I. synthesis of platelet protein in a cell-free system. Biochim Biophys Acta 1968; 166: 689-97.
    CrossrefPubMedGoogle Scholar
  • 11 Booyse FM, Hoveke TP, Rafelson Jr. ME. Studies on human platelets. II. Protein synthetic activity of various platelet populations. Biochim Biophys Acta 1968; 157: 660-3.
    CrossrefPubMedGoogle Scholar
  • 12 Kieffer N, Guichard J, Farcet JP. et al. Biosynthesis of major platelet proteins in human blood platelets. Eur J Biochem 1987; 164: 189-95.
    CrossrefPubMedGoogle Scholar
  • 13 Ts’ao CH. Rough endoplasmic reticulum and ribosomes in blood platelets. Scand J Haematol 1971; 8: 134-40.
    CrossrefPubMedGoogle Scholar
  • 14 Newman PJ, Gorski J, White 2nd GC. et al. Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction. J Clin Invest 1988; 82: 739-43.
    CrossrefPubMedGoogle Scholar
  • 15 Santoso S, Kalb R, Kiefel V. et al. The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis. Br J Haematol 1993; 84: 451-6.
    CrossrefPubMedGoogle Scholar
  • 16 Gnatenko DV, Dunn JJ, McCorkle SR. et al. Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood 2003; 101: 2285-93.
    CrossrefPubMedGoogle Scholar
  • 17 Bugert P, Dugrillon A, Gunaydin A. et al. Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost 2003; 90: 738-48.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Lindemann S, Tolley ND, Dixon DA. et al. Activated platelets mediate inflammatory signaling by regulated interleukin 1beta synthesis. J Cell Biol 2001; 154: 485-90.
    CrossrefPubMedGoogle Scholar
  • 19 Lindemann S, Tolley ND, Eyre JR. et al. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control. J Biol Chem 2001; 276: 33947-51.
    CrossrefPubMedGoogle Scholar
  • 20 Weyrich AS, Dixon DA, Pabla R. et al. Signal-dependent translation of a regulatory protein, Bcl-3, in activated human platelets. Proc Natl Acad Sci U S A 1998; 95: 5556-61.
    CrossrefPubMedGoogle Scholar
  • 21 Pabla R, Weyrich AS, Dixon DA. et al. Integrindependent control of translation: engagement of integrin alphaIIbbeta3 regulates synthesis of proteins in activated human platelets. J Cell Biol 1999; 144: 175-84.
    CrossrefPubMedGoogle Scholar
  • 22 Bessler H, Agam G, Djaldetti M. Increased protein synthesis by human platelets during phagocytosis of latex particles in vitro. Thromb Haemost 1976; 35: 350-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Plow EF. Extracellular factors influencing the in vitro protein synthesis of platelets. Thromb Haemost 1979; 42: 666-78.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Weyrich AS, Lindemann S, Zimmerman GA. The evolving role of platelets in inflammation. J Thromb Haemost 2003; 1: 1897-905.
    CrossrefPubMedGoogle Scholar
  • 25 Kramer RM, Roberts EF, Strifler BA. et al. Thrombin induces activation of p38 MAP kinase in human platelets. J Biol Chem 1995; 270: 27395-8.
    CrossrefPubMedGoogle Scholar
  • 26 Nicholas HR, Hodgkin J. Innate immunity: the worm fights back. Curr Biol 2002; 12: R731-2.
    CrossrefPubMedGoogle Scholar
  • 27 Pandey A, Mann M. Proteomics to study genes and genomes. Nature 2000; 405: 837-46.
    CrossrefPubMedGoogle Scholar
  • 28 O’Farrell PH. High resolution two-dimensional electrophoresis of proteins. J Biol Chem 1975; 250: 4007-21.
    PubMedGoogle Scholar
  • 29 Jung E, Heller M, Sanchez JC. et al. Proteomics meets cell biology: the establishment of subcellular proteomes. Electrophoresis 2000; 21: 3369-77.
    CrossrefPubMedGoogle Scholar
  • 30 Clemetson K. Platelet Membrane Glycoproteins.. Plenum Press; 1985: 51-85.
  • 31 Gravel P, Sanchez JC, Walzer C. et al. Human blood platelet protein map established by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 1995; 16: 1152-9.
    CrossrefPubMedGoogle Scholar
  • 32 Hanash SM, Neel JV, Baier LJ. et al. Genetic analysis of thirty-three platelet polypeptides detected in twodimensional polyacrylamide gels. Am J Hum Genet 1986; 38: 352-60.
    PubMedGoogle Scholar
  • 33 Giometti CS, Anderson NG. Protein changes in activated human platelets. Clin Chem 1984; 30: 2078-83.
    PubMedGoogle Scholar
  • 34 Yates 3rd. JR. Mass spectral analysis in proteomics. Annu Rev Biophys Biomol Struct 2004; 33: 297-316.
    CrossrefPubMedGoogle Scholar
  • 35 Fenn JB, Mann M, Meng CK. et al. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989; 246: 64-71.
    CrossrefPubMedGoogle Scholar
  • 36 Hillenkamp F, Karas M, Beavis RC. et al. Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers. Anal Chem 1991; 63: 1193A-1203A.
    CrossrefPubMedGoogle Scholar
  • 37 Gevaert K, Eggermont L, Demol H. et al. A fast and convenient MALDI-MS based proteomic approach: identification of components scaffolded by the actin cytoskeleton of activated human thrombocytes. J Biotechnol 2000; 78: 259-69.
    CrossrefPubMedGoogle Scholar
  • 38 Marcus K, Immler D, Sternberger J. et al. Identification of platelet proteins separated by two-dimensional gel electrophoresis and analyzed by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and detection of tyrosine-phosphorylated proteins. Electrophoresis 2000; 21: 2622-36.
    CrossrefPubMedGoogle Scholar
  • 39 O’Neill EE, Brock CJ, von Kriegsheim AF. et al. Towards complete analysis of the platelet proteome. Proteomics 2002; 2: 288-305.
    CrossrefPubMedGoogle Scholar
  • 40 Garcia A, Prabhakar S, Brock CJ. et al. Extensive analysis of the human platelet proteome by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 2004; 4: 656-68.
    CrossrefPubMedGoogle Scholar
  • 41 Gevaert K, Ghesquiere B, Staes A. et al. Reversible labeling of cysteine-containing peptides allows their specific chromatographic isolation for non-gel proteome studies. Proteomics 2004; 4: 897-908.
    CrossrefPubMedGoogle Scholar
  • 42 Gevaert K, Goethals M, Martens L. et al. Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol 2003; 21: 566-9.
    CrossrefPubMedGoogle Scholar
  • 43 Marcus K, Moebius J, Meyer HE. Differential analysis of phosphorylated proteins in resting and thrombin-stimulated human platelets. Anal Bioanal Chem 2003; 376: 973-93.
    CrossrefPubMedGoogle Scholar
  • 44 Maguire PB, Fitzgerald DJ. Platelet proteomics. J Thromb Haemost 2003; 1: 1593-601.
    CrossrefPubMedGoogle Scholar
  • 45 Garcia A, Prabhakar S, Hughan S. et al. Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins. Blood 2004; 103: 2088-95.
    CrossrefPubMedGoogle Scholar
  • 46 Coppinger JA, Cagney G, Toomey S. et al. Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions. Blood 2004; 103: 2096-104.
    CrossrefPubMedGoogle Scholar
  • 47 Massberg S, Brand K, Gruner S. et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med 2002; 196: 887-96.
    CrossrefPubMedGoogle Scholar
  • 48 Huo Y, Ley KF. Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 2004; 14: 18-22.
    CrossrefPubMedGoogle Scholar
  • 49 Garcia BA, Smalley DM, Cho HJ. et al. The Platelet Microparticle Proteome. J. Proteome Res. 2005 (in press).
    PubMedGoogle Scholar
  • 50 Moebius J, Zahedi RP, Lewandrowski UU. et al. The human platelet membrane proteome reveals several new potential membrane proteins. Mol Cell Proteomics. 2005 (in press).
    PubMedGoogle Scholar
  • 51 Huber W, Gentleman R. matchprobes: a Bioconductor package for the sequence-matching of microarray probe elements. Bioinformatics 2004; 20: 1651-2.
    CrossrefPubMedGoogle Scholar
  • 52 Dandekar T, Sauerborn R. Comparative genome analysis and pathway reconstruction. Pharmacogenomics 2002; 3: 245-56.
    CrossrefPubMedGoogle Scholar
  • 53 Frishman D, Mokrejs M, Kosykh D. et al. The PEDANT genome database. Nucleic Acids Res 2003; 31: 207-11.
    CrossrefPubMedGoogle Scholar
  • 54 Gaasterland T, Sensen CW. MAGPIE: automated genome interpretation. Trends Genet 1996; 12: 76-8.
    CrossrefPubMedGoogle Scholar
  • 55 Gaasterland T, Sensen CW. Fully automated genome analysis that reflects user needs and preferences. A detailed introduction to the MAGPIE system architecture. Biochimie 1996; 78: 302-10.
    CrossrefPubMedGoogle Scholar
  • 56 Meyer F, Goesmann A, McHardy AC. et al. GenDB– an open source genome annotation system for prokaryote genomes. Nucleic Acids Res 2003; 31: 2187-95.
    CrossrefPubMedGoogle Scholar
  • 57 Krishnamurthy L, Nadeau J, Ozsoyoglu G. et al. Pathways database system: an integrated system for biological pathways. Bioinformatics 2003; 19: 930-7.
    CrossrefPubMedGoogle Scholar
  • 58 Pfeiffer T, Sanchez-Valdenebro I, Nuno JC. et al. METATOOL: for studying metabolic networks. Bioinformatics 1999; 15: 251-7.
    CrossrefPubMedGoogle Scholar
  • 59 Bengert P, Dandekar T. A software tool-box for analysis of regulatory RNA elements. Nucleic Acids Res 2003; 31: 3441-5.
    CrossrefPubMedGoogle Scholar
  • 60 Altschul SF, Madden TL, Schaffer AA. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25: 3389-402.
    CrossrefPubMedGoogle Scholar
  • 61 Hulo N, Sigrist CJ, Le Saux V. et al. Recent improvements to the PROSITE database. Nucleic Acids Res 2004; 32 Database issue: D134-7.
    CrossrefPubMedGoogle Scholar
  • 62 Moller S, Croning MD, Apweiler R. Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics 2001; 17: 646-53.
    CrossrefPubMedGoogle Scholar
  • 63 Rost B, Yachdav G, Liu J. The PredictProtein server. Nucleic Acids Res 2004; 32: W321-6.
    CrossrefPubMedGoogle Scholar
  • 64 Schmidt S, Bork P, Dandekar T. A versatile structural domain analysis server using profile weight matrices. J Chem Inf Comput Sci 2002; 42: 405-7.
    CrossrefPubMedGoogle Scholar
  • 65 Letunic I, Copley RR, Schmidt S. et al. SMART 4.0: towards genomic data integration. Nucleic Acids Res 2004; 32: D142-4.
    CrossrefPubMedGoogle Scholar
  • 66 Tatusov RL, Fedorova ND, Jackson JD. et al. The COG database: an updated version includes eukaryotes. BMC Bioinformatics 2003; 4: 41.
    CrossrefPubMedGoogle Scholar
  • 67 Dandekar T, Snel B, Huynen M. et al. Conservation of gene order: a fingerprint of proteins that physically interact. Trends Biochem Sci 1998; 23: 324-8.
    CrossrefPubMedGoogle Scholar
  • 68 von Mering C, Huynen M, Jaeggi D. et al. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res 2003; 31: 258-61.
    CrossrefPubMedGoogle Scholar
  • 69 Brown EJ, Schreiber SL. A signaling pathway to translational control. Cell 1996; 86: 517-20.
    CrossrefPubMedGoogle Scholar
  • 70 Eisenhaber F. Discovering Biomolecular Mechanisms with computational biology.. Georgetown, Texas: Landes Biosciences; 2005
  • 71 Schuster S, Fell D, Pfeiffer T. et al. Elementary modes analysis illustrated with human red cell metabolism. Biothermokinetics in the post genomic era.. Chalmers; 1998: 332-9.
    Google Scholar
  • 72 Michno A, Skibowska A, Raszeja-Specht A. et al. The role of adenosine triphosphate citrate lyase in the metabolism of acetyl coenzyme a and function of blood platelets in diabetes mellitus. Metabolism 2004; 53: 66-72.
    CrossrefPubMedGoogle Scholar
  • 73 Sutherland M, Shankaranarayanan P, Schewe T. et al. Evidence for the presence of phospholipid hydroperoxide glutathione peroxidase in human platelets: implications for its involvement in the regulatory network of the 12-lipoxygenase pathway of arachidonic acid metabolism. Biochem J 2001; 353: 91-100.
    CrossrefPubMedGoogle Scholar
  • 74 Kroetz DL, Xu F. Regulation and Inhibition of Arachidonic Acid -Hydroxylases and 20-HETE Formation. Annu Rev Pharmacol Toxicol 2005; 45: 413-38.
    CrossrefPubMedGoogle Scholar
  • 75 Loscalzo J. Oxidant stress: a key determinant of atherothrombosis. Biochem Soc Trans 2003; 31: 1059-61.
    CrossrefPubMedGoogle Scholar
  • 76 Seno T, Inoue N, Gao D. et al. Involvement of NADH/NADPH oxidase in human platelet ROS production. Thromb Res 2001; 103: 399-409.
    CrossrefPubMedGoogle Scholar
  • 77 Borsig L, Wong R, Hynes RO. et al. Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci U S A 2002; 99: 2193-8.
    CrossrefPubMedGoogle Scholar
  • 78 Manegold PC, Hutter J, Pahernik SA. et al. Plateletendothelial interaction in tumor angiogenesis and microcirculation. Blood 2003; 101: 1970-6.
    CrossrefPubMedGoogle Scholar
  • 79 Kim YJ, Borsig L, Varki NM. et al. P-selectin deficiency attenuates tumor growth and metastasis. Proc Natl Acad Sci U S A 1998; 95: 9325-30.
    CrossrefPubMedGoogle Scholar
  • 80 Borsig L, Wong R, Feramisco J. et al. Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci U S A 2001; 98: 3352-7.
    CrossrefPubMedGoogle Scholar
  • 81 Zimmerman GA. Two by two: the pairings of P-selectin and P-selectin glycoprotein ligand 1. Proc Natl Acad Sci U S A 2001; 98: 10023-4.
    CrossrefPubMedGoogle Scholar
  • 82 Bromberg ME, Sundaram R, Homer RJ. et al. Role of tissue factor in metastasis: functions of the cytoplasmic and extracellular domains of the molecule. Thromb Haemost 1999; 82: 88-92.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 83 Camerer E, Qazi AA, Duong DN. et al. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 2004; 104: 397-401.
    CrossrefPubMedGoogle Scholar
  • 84 Hamada K, Kuratsu J, Saitoh Y. et al. Expression of tissue factor correlates with grade of malignancy in human glioma. Cancer 1996; 77: 1877-83.
    CrossrefPubMedGoogle Scholar
  • 85 Kakkar AK, Lemoine NR, Scully MF. et al. Tissue factor expression correlates with histological grade in human pancreatic cancer. Br J Surg 1995; 82: 1101-4.
    CrossrefPubMedGoogle Scholar
  • 86 Seto S, Onodera H, Kaido T. et al. Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis. Cancer 2000; 88: 295-301.
    CrossrefPubMedGoogle Scholar
  • 88 Sawada M, Miyake S, Ohdama S. et al. Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis. Br J Cancer 1999; 79: 472-7.
    CrossrefPubMedGoogle Scholar
  • 89 Mueller BM, Ruf W. Requirement for binding of catalytically active factor VIIa in tissue factor-dependent experimental metastasis. J Clin Invest 1998; 101: 1372-8.
    CrossrefPubMedGoogle Scholar
  • 90 Bromberg ME, Konigsberg WH, Madison JF. et al. Tissue factor promotes melanoma metastasis by a pathway independent of blood coagulation. Proc Natl Acad Sci U S A 1995; 92: 8205-9.
    CrossrefPubMedGoogle Scholar
  • 91 Esumi N, Fan D, Fidler IJ. Inhibition of murine melanoma experimental metastasis by recombinant desulfatohirudin, a highly specific thrombin inhibitor. Cancer Res 1991; 51: 4549-56.
    PubMedGoogle Scholar
  • 92 Mueller BM, Reisfeld RA, Edgington TS. et al. Expression of tissue factor by melanoma cells promotes efficient hematogenous metastasis. Proc Natl Acad Sci U S A 1992; 89: 11832-6.
    CrossrefPubMedGoogle Scholar
  • 93 Fischer EG, Riewald M, Huang HY. et al. Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor. J Clin Invest 1999; 104: 1213-21.
    CrossrefPubMedGoogle Scholar
  • 94 Donnelly KM, Bromberg ME. Milstone et al. Ancylostoma caninum anticoagulant peptide blocks metastasis in vivo and inhibits factor Xa binding to melanoma cells in vitro. Thromb Haemost 1998; 79: 1041-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 95 Crissman JD, Hatfield J, Schaldenbrand M. et al. Arrest and extravasation of B16 amelanotic melanoma in murine lungs. A light and electron microscopic study. Lab Invest 1985; 53: 470-8.
    PubMedGoogle Scholar
  • 96 Al-Mehdi AB, Tozawa K, Fisher AB. et al. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 2000; 6: 100-2.
    CrossrefPubMedGoogle Scholar
  • 97 Trikha M, Nakada MT. Platelets and cancer: implications for antiangiogenic therapy. Semin Thromb Hemost 2002; 28: 39-44.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 98 Sorensen HT, Johnsen SP, Norgard B. et al. Cancer and venous thromboembolism: a multidisciplinary approach. Clin Lab 2003; 49: 615-23.
    PubMedGoogle Scholar
  • 99 Pinzon R, Drewinko B, Trujillo JM. et al. Pancreatic carcinoma and Trousseau’s syndrome: experience at a large cancer center. J Clin Oncol 1986; 4: 509-14.
    CrossrefPubMedGoogle Scholar