Abstract
Stroke is a disease that affects the blood vessels that supply blood to the brain. Although platelets are implicated in the pathophysiology of stroke the mechanism is still not clear and there antiplatelet agents available for the prevention and treatment of stroke. We herein examined the relationship between the potential cytokine, TNF-α platelet activation and apoptosis in acute ischemic stroke patients. We selected 60 patients (mean age 57.9 ± 10.2 years) who had not taken any antiplatelet drugs for 14 days. A group of 45 participants (mean age 51.05 ± 9.07 years) were selected as the control group. For both the patients and for the control group, P-selectin (CD62p) and Annexin-V binding, cytochrome-c levels, caspase-3 gene expression and caspase-3 releasing and plasma TNF-α levels were measured in platelets. The results showed significant increase in plasma TNF-α and platelet Annexin-V, CD62p, cytochrome-c and caspase-3 gene expression in stroke patients compared to the control group. The data of this work suggests that inflammation may have a role in platelet apoptosis in stroke which may suggest a new aspect of the role of inflammation in the development of acute ischemic stroke.
Similar content being viewed by others
References
Norrving B, Kissela B (2013) The global burden of stroke and need for a continuum of care. Neurology 80(3):5–12
Smith NM, Pathansali R, Bath PMW (1999) Platelets and stroke. Vasc Med 4:165–172
Yago T, Tsukuda M, Minami M (1999) P-selectin binding promotes the adhesion of monocytes to VCAM-1 under flow conditions. J Immunol 163:367–373
del Zoppo GJ (1998) The role of platelets in ischemic stroke. Neurology 51(3):9–14
Gyulkhandanyan AV, Mutlu A, Freedman J, Leytin V (2012) Markers of platelet apoptosis: methodology and applications. J Thromb Thrombolysis 33(4):397–411
Leytin V, Allen DJ, Mutlu A, Gyulkhandanyan AV, Mykhaylov S, Freedman J (2009) Mitochondrial control of platelet apoptosis: effect of cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. Lab Invest 89(4):374–384
Vogler M, Hamali HA, Sun XM, Bampton ET, Dinsdale D, Snowden RT, Dyer MJ, Goodall AH, Cohen GM (2011) BCL2/BCL-XL inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation. Blood 117(26):7145–7154
Gawaz M, Langer H, May AE (2005) Platelets in inflammation and atherogenesis. J Clin Invest 115(12):3378–3384
Morrell CN, Sun H, Swaim AM, Baldwin WM (2007) Platelets an inflammatory force in transplantation. Am J Transplant 7(11):2447–2454
Baund V, Karin M (2001) Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11(9):372–377
Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10(1):45–65
Herbein G, Khan KA (2008) Is HIV infection a TNF receptor signaling-driven disease? Trends Immunol 29(2):61–67
Park KM, Bowers WJ (2010) Tumor necrosis factor-alpha mediated signaling in neuronal homeostasis and dysfunction. Cell Signal 22(7):977–983
Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28(6):1233–1244
Watters O, OConnor JJ (2011) A role for tumor necrosis factor-α in ischemia and ischemic preconditioning. J Neuroinflammation 8:87. doi:10.1186/1742-2094-8-87
Tarkowski E, Rosengren L, Blomstrand C, Jensen C, Ekholm S, Tarkowski A (1999) Intrathecal expression of proteins regulating apoptosis in acute stroke. Stroke 30(2):321–327
Heldmann U, Thored P, Claasen JH, Arvidsson A, Kokaia Z, Lindvall O (2005) TNF-alpha antibody infusion impairs survival of stroke-generated neuroblasts in adult rat brain. Exp Neurol 196(1):204–208
Zaremba J, Losy J (2001) Early TNF-α levels correlate with ischaemic stroke severity. Acta Neurol Scand 104:288–295
Sener A, Cevik O, Yanikkaya-Demirel G, Apikoglu-Rabus S, Ozsavci D (2012) Influence of Platelet γ-Glutamyltransferase on Oxidative Stress and Apoptosis in the Presence of Holo-Transferrin. Folia Biol (Praha) 58(5):193–202
Erşahin M, Çevik Ö, Akakın D, Şener A, Özbay L, Yegen BC, Şener G (2012) Montelukast inhibits caspase-3 activity and ameliorates oxidative damage in the spinal cord and urinary bladder of rats with spinal cord injury. Prostaglandins Other Lipid Mediat 99(3–4):131–139
Cevik O, Adiguzel Z, Baykal AT, Sener A (2012) Caspase-3 gene expression in adenosine diphosphate stimulated platelets. J Clin Exp Invest 3(3):372–377
Nieswandt B, Pleines I, Bender M (2011) Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke J. Thromb Haemost 9(1):92–104
Nilupul Perera M, Ma HK, Arakawa S, Howells DW, Markus R, Rowe CC, Donnan GA (2006) Inflammation following stroke. J Clin Neurosci 13(1):1–8
Ferrarese C, Mascarucci P, Zoia C, Cavarretta R, Frigo M, Begni B, Sarinella F, Frattola L, De Simoni MG (1999) Increased cytokine release from peripheral blood cells after acute stroke. J Cereb Blood Flow Metab 19(9):1004–1009
Al-Bahrani A, Taha S, Shaath H, Bakhiet M (2007) TNF-alpha and IL-8 in acute stroke and the modulation of these cytokines by antiplatelet agents. Curr Neurovasc Res 4(1):31–37
Renesto P, Chignard M (1991) Tumor necrosis factor-alpha enhances platelet activation via cathepsin G released from neutrophils. J Immunol 146(7):2305–2309
Pignatelli P, De Biase L, Lenti L, Tocci G, Brunelli A, Cangemi R, Riondino S, Grego S, Volpe M, Violi F (2005) Tumor necrosis factor-alpha as trigger of platelet activation in patients with heart failure. Blood 106(6):1992–1994
Nagahama M, Nomura S, Ozaki Y, Yoshimura C, Kagawa H, Fukuhara S (2001) Platelet activation markers and soluble adhesion molecules in patients with systemic lupus erythematosus. Autoimmunity 33(2):85–94
Massberg S, Enders G, Leiderer R, Eisenmenger S, Vestweber D, Krombach F, Messmer K (1998) Platelet-endothelial cell interactions during ischemia/reperfusion: the role of P-selectin. Blood 92:507–515
Michelson AD (1996) Flow cytometry: a clinical test of platelet function. Blood 87:4925–4936
Belniak-Legieć E, Stelmasiak Z (2000) Blood platelet activation markers in patients with acute cerebral infarction during the earliest stage of the disease–evaluation using flow cytometry methods. Neurol Neurochir Pol 34(5):853–864
Jaremo P, Eriksson M, Lindahl TL, Nilsson S, Milovanovic M (2012) Platelets and acute cerebral infarction. Platelets. doi: 10.3109/09537104.2012.712168
Tait JF, Smith C, Wood BL (1999) Measurement of phosphatidylserine exposure in leukocytes and platelets by whole-blood flow cytometry with annexin V. Blood Cells Mol Dis 25(5–6):271–278
Ramstrom S, O’Neill S, Dunne E, Kenny D (2010) Annexin V binding to platelets is agonist, time and temperature dependent. Platelets 21(4):289–296
Blankenberg FG (2008) In vivo detection of apoptosis. J Nucl Med 49(2):81–95
Serebruany V, Malinin A, Ziai W, Atar D, Pokov A, Jilma B, Hanley D (2006) Dipyridamole decreases protease-activated receptor and annexin-v binding on platelets of post stroke patients with aspirin nonresponsiveness. Cerebrovasc Dis 21(1–2):98–105
Chu WM (2013) Tumor necrosis factor. Cancer Lett 328(2):222–225
Bradham CA, Qian T, Streetz K, Trautwein C, Brenner DA, Lemasters JJ (1998) The mitochondrial permeability transition is required for tumor necrosis factor alpha-mediated apoptosis and cytochrome c release. Mol Cell Biol 18(11):6353–6364
Tafani M, Schneider TG, Pastorino JG, Farber JL (2000) Cytochrome c-dependent activation of caspase-3 by tumor necrosis factor requires induction of the mitochondrial permeability transition. Am J Pathol 156(6):2111–2121
Leytin V, Allen DJ, Mutlu A, Gyulkhandanyan AV, Mykhaylov S, Freedman J (2009) Mitochondrial control of platelet apoptosis: effect of cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. Lab Invest 89(4):374–384
Acknowledgments
This study was funded by the Marmara University Research Unit (Grant No. SAG-C-DRP-010710-0216).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Cevik, O., Adiguzel, Z., Baykal, A.T. et al. The apoptotic actions of platelets in acute ischemic stroke. Mol Biol Rep 40, 6721–6727 (2013). https://doi.org/10.1007/s11033-013-2787-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-013-2787-9