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2012 | 61 | 3 | 445-454
Article title

Komórkowa odpowiedź na działanie trombiny

Content
Title variants
EN
Cellular response to thrombin action.
Languages of publication
PL EN
Abstracts
PL
Trombina jest osoczową proteazą serynową generowaną podczas kaskady krzepnięcia krwi. Aktywna ludzka a-trombina posiada masę 37 kDa i jest zbudowana z 2 polipeptydowych łańcuchów (A i B) połączonych są ze sobą kowalencyjnym wiązaniem disiarczkowym. Trombina jest głównie kojarzona z procesami krzepnięcia i fibrynolizy, jednak enzym ten jest również zdolny do wywoływania biologicznej odpowiedzi różnych komórek znajdujących się w pobliżu miejsca jej tworzenia. Odpowiedź ta następuje poprzez receptory aktywowane przez proteazy (PAR - ang. Protease-Activated Receptor), które należą do rodziny 7 transbłonowych receptorów związanych z białkami G (GPCR - ang. G Protein-Coupled Receptor). Dużą ekspresję receptorów PAR wykazują płytki krwi, komórki śródbłonka naczyń krwionośnych, monocyty, limfocyty T, neutrofile, fibroblasty, komórki mięśniowe, komórki układu nerwowego, a także komórki nowotworowe. Trombina wywołuje aktywację płytek krwi prowadząc do ich agregacji, zmiany kształtu i sekrecji zawartości znajdujących się w ziarnistościach płytkowych. Komórki śródbłonka aktywowane przez trombinę wykazują na swojej powierzchni ekspresję P-selektyny, E-selektyny i białek adhezyjnych (ICAM-1 i VCAM-1). Aktywacja receptora PAR-1 na monocytach skutkuje wzrostem wydzielania prozapalnych cytokin przez te komórki. Przekazywanie sygnału poprzez receptory PAR stymuluje wzrost, różnicowanie i proliferacje komórek, co ma duże znaczenie podczas regeneracji tkanek. Trombina również sprzyja procesowi angiogenezy podczas rozwoju nowotworu, co ułatwia przeżutowaniu. Ten szeroki aspekt działania trombiny wskazuje, że enzym ten jest wielofunkcyjną proteazą serynową.
EN
Thrombin is plasma serine protease generated in the blood coagulation cascade. Active form of human thrombin: α-thrombin is a 36 kDa molecule consisting of 2 polypeptide chains (A and B) covalently linked by a single disulfide bond. Thrombin is mostly associated with blood coagulation and fibrinolysis. However, thrombin is also able to induce biological responses of different cells presented in the vicinity of enzyme generation. These responses are mediated by protease activated receptors (PAR), which are members of the 7-transmembrane G protein coupled receptors family. PARs are abundantly presented on blood platelets, endothelial cells, monocytes, T-lymphocytes, fibroblast, smooth muscle cells, neurons and tumor cells. Thrombin stimulates platelets activation leading to their aggregation, shape change and secretion of the contents of platelet granules. PAR activation on endothelial cells and blood vessels smooth muscle cells causes vasodilation. Endothelial cells activated by thrombin also exhibit on their surface expression of P-selectin, E-selectin and adhesion molecules (ICAM-1 and VCAM-1). Activation of PAR-1 receptor in monocytes results in increased secretion of proinflammatory cytokines. PAR signaling stimulates cell growth, differentiation and proliferation. These effects are important in healing of injured tissues. Thrombin promotes angiogenesis in developing tumors and facilitates their metastasis. The different effects of thrombin action indicate that this enzyme is one of the most multifunctional serine protease.
Keywords
Journal
Year
Volume
61
Issue
3
Pages
445-454
Physical description
Dates
published
2012
Contributors
author
  • Katedra Biochemii Ogólnej, Uniwersytet Łódzki, Pomorska 141/143, 90-236 Łódź, Polska
  • Katedra Biochemii Ogólnej, Uniwersytet Łódzki, Pomorska 141/143, 90-236 Łódź, Polska
author
  • Katedra Biochemii Ogólnej, Uniwersytet Łódzki, Pomorska 141/143, 90-236 Łódź, Polska
References
  • Adam F., Bouton M. C., Huisse M. G., Jandrot-Perrus M., 2003. Thrombin interaction with platelet membrane glycoprotein Ib alpha. Trends Mol. Med. 9, 461-464.
  • Adams T. E., Huntington J. A., 2006. Thrombin-cofactor interactions: structural insights into regulatory mechanisms. Arterioscler. Thromb. Vasc. Biol. 26, 1738-1745.
  • Becker R. C., Spencer F. A., 1998. Thrombin: structure, biochemistry, measurement, and status in clinical medicine. J. Thromb. Thrombolysis. 5, 215-229.
  • Bijak M., Bobrowski M., 2010 Znaczenie inhibitorów trombiny w farmakoterapii przeciwzakrzepowej. Postępy Nauk Medycznych. 10, 819-825.
  • Bode W., 2006. Structure and interaction modes of thrombin. Blood Cells Mol. Dis. 36, 122-130.
  • Brass L. F., 2003. Thrombin and platelet activation. Chest 124, 18-25.
  • Brass S., 2001. Cardiovascular biology. Platelets and proteases. Nature 413, 26-27.
  • Brophy C. M., Woodrum D., Dickinson M., Beall A., 1998. Thrombin activates MAPKAP2 kinase in vascular smooth muscle. J. Vasc. Surg. 27, 963-969.
  • Carter W. J., Cama E., Huntington J. A., 2005. Crystal structure of thrombin bound to heparin. J. Biol. Chem. 280, 2745-2749.
  • Chambers R. C., Leoni P., Blanc-Brude O. P., Wembridge D. E., Laurent G. J., 2000. Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-1. J. Biol. Chem. 275, 35584-35591.
  • Coughlin S. R., 2001. Protease-activated receptors in vascular biology. Thromb. Haemost. 86, 298-307.
  • Coughlin S. R., Camerer E., 2003. PARticipation in inflammation. J. Clin. Invest 111, 25-27.
  • Crawley J. T., Zanardelli S., Chion C. K., Lane D. A., 2007. The central role of thrombin in hemostasis. J. Thromb. Haemost. 5, 95-101.
  • De Cristofaro R., De Candia E., 2003. Thrombin domains: structure, function and interaction with platelet receptors. J. Thromb. Thrombolysis. 15, 151-163.
  • Dery O., Corvera C. U., Steinhoff M., Bunnett N. W., 1998. Proteinase-activated receptors: novel mechanisms of signaling by serine proteases. Am. J. Physiol 274, 1429-1452.
  • Di Cera E., 2003. Thrombin interactions. Chest 124, 11-17.
  • Di Cera E., 2008. Thrombin. Mol. Aspects Med. 29, 203-254.
  • Di Cera E., Guinto E. R., Vindigni A., Dang Q. D., Ayala Y. M., Wuyi M., Tulinsky A., 1995. The Na+ binding site of thrombin. J. Biol. Chem. 270, 22089-22092.
  • Dugina T. N., Kiseleva E. V., Chistov I. V., Umarova B. A., Strukova S. M., 2002. Receptors of the PAR family as a link between blood coagulation and inflammation. Biochem. (Mosc.) 67, 65-74.
  • Esmon C. T., 2004. Crosstalk between inflammation and thrombosis. Maturitas 47, 305-314.
  • Goldsack N., Chambers R., Dabbagh K., Laurent G., 1998. Molecule in focus Thrombin. Int. J. Biochem. Cell. Biol. 30, 641-646.
  • Hansen K. K., Oikonomopoulou K., Li Y., Hollenberg M. D., 2008. Proteinases, proteinase-activated receptors (PARs) and the pathophysiology of cancer and diseases of the cardiovascular, musculoskeletal, nervous and gastrointestinal systems. Naunyn Schmiedebergs Arch. Pharmacol. 377, 377-392.
  • Hirano K., Kanaide H., 2003. Role of protease-activated receptors in the vascular system. J. Atheroscler. Thromb. 10, 211-225.
  • Hollenberg M. D., Houle S., 2005. Proteinases as hormone-like signal messengers. Swiss. Med. Wkly. 135, 425-432.
  • Houliston R. A., Keogh R. J., Sugden D., Dudhia J., Carter T. D., Wheeler-Jones C. P., 2002. Protease-activated receptors upregulate cyclooxygenase-2 expression in human endothelial cells. Thromb. Haemost. 88, 321-328.
  • Huntington J. A., 2008. How Na+ activates thrombin - a review of the functional and structural data. Biol. Chem. 389, 1025-1035.
  • Kawabata A., Kuroda R., 2000. Protease-activated receptor (PAR), a novel family of G protein-coupled seven trans-membrane domain receptors: activation mechanisms and physiological roles. Jpn. J. Pharmacol. 82, 171-174.
  • Knoepp L., Bagwell C. D., Garlich P., Brophy C. M., 1999. Thrombin contraction of vascular smooth muscle: implications for vasospasm. Int. J. Surg. Investig. 1, 285-290.
  • Lane D. A., Philippou H., Huntington J. A., 2005. Directing thrombin. Blood 106, 2605-2612.
  • Lapetina E. G., 1990. The signal transduction induced by thrombin in human platelets. FEBS Lett. 268, 400-404.
  • Licari L. G., Kovacic J. P., 2009. Thrombin physiology and pathophysiology. J. Vet. Emerg. Crit Care (San. Antonio.) 19, 11-22.
  • Luo W., Wang Y., Reiser G., 2007. Protease-activated receptors in the brain: receptor expression, activation, and functions in neurodegeneration and neuroprotection. Brain Res. Rev. 56, 331-345.
  • Macfarlane S. R., Seatter M. J., Kanke T., Hunter G. D., Plevin R., 2001. Proteinase-activated receptors. Pharmacol. Rev. 53, 245-282.
  • Mackie E. J., Pagel C. N., Smith R., De Niese M. R., Song S. J., Pike R. N., 2002. Protease-activated receptors: a means of converting extracellular proteolysis into intracellular signals. IUBMB. Life 53, 277-281.
  • Maragoudakis M. E., Tsopanoglou N. E., Andriopoulou P., Maragoudakis M. M., 2000. Effects of thrombin/thrombosis in angiogenesis and tumour progression. Matrix Biol. 19, 345-351.
  • Nathan C., Xie Q. W., 1994. Regulation of biosynthesis of nitric oxide. J. Biol. Chem. 269, 13725-13728.
  • Offermanns S., 2006. Activation of platelet function through G protein-coupled receptors. Circ. Res. 99, 1293-1304.
  • Olas B., 2001. Involvement of heterotrimeric G proteins in signal transduction in blood platelets. Acta Haemat. Pol. 32, 393-405.
  • Olas B., Wachowicz B., 1998. The role of thrombin in hemostasis. Postepy Hig. Med. Dosw. 52, 471-487.
  • Ossovskaya V. S., Bunnett N. W., 2004. Protease-activated receptors: contribution to physiology and disease. Physiol Rev. 84, 579-621.
  • Palatyńska-Ulatowska A., Michalska M., Michalski Ł., Pawlicka H., 2007. Trombina i fibryna w procesach angiogenezy tkanek zębów i przyzębia - przegląd piśmiennictwa. Dent. Med. Probl. 3, 307-313.
  • Patterson C., Stouffer G. A., Madamanchi N., Runge M. S., 2001. New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology. Circ. Res. 88, 987-997.
  • Ramachandran R., Hollenberg M. D., 2008. Proteinases and signalling: pathophysiological and therapeutic implications via PARs and more. Br. J. Pharmacol. 153 263-282.
  • Sanner M. F., 1999. Python: a programming language for software integration and development. J. Mol. Graph. Model. 17, 57-61.
  • Sawicka B., 2000. Rozsiane wykrzepianie wewnątrznaczyniowe: aspekty kliniczne, laboratoryjne i terapeutyczne. Post. Nauk. Med. 3, 40-50.
  • Schmidlin F., Bunnett N. W., 2001. Protease-activated receptors: how proteases signal to cells. Curr. Opin. Pharmacol. 1, 575-582.
  • Shrivastava S., McVey J. H., Dorling A., 2007. The interface between coagulation and immunity. Am. J. Transplant. 7, 499-506.
  • Steinberg S. F., 2005. The cardiovascular actions of protease-activated receptors. Mol. Pharmacol. 67, 2-11.
  • Steinhoff M., Buddenkotte J., Shpacovitch V., Rattenholl A., Moormann C., Vergnolle N., Luger T. A., Hollenberg M. D., 2005. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr. Rev. 26, 1-43.
  • Strukova S. M., 2001. Thrombin as a regulator of inflammation and reparative processes in tissues. Biochem. (Mosc.) 66, 8-18.
  • Suo Z., Citron B. A., Festoff B. W., 2004. Thrombin: a potential proinflammatory mediator in neurotrauma and neurodegenerative disorders. Curr. Drug Targets. Inflamm. Allergy 3, 105-114.
  • Trejo J., 2003. Protease-activated receptors: new concepts in regulation of G protein-coupled receptor signaling and trafficking. J. Pharmacol. Exp. Ther. 307, 437-442.
  • Weber D. S., Griendling K. K., 2004. Thrombin: beyond coagulation. J. Mol. Cell Cardiol. 36, 13-15.
  • Wright J. H., Minot G. R., 1917. The Viscous Metamorphosis of the Blood Platelets. J. Exp. Med. 26, 395-409.
  • Xi G., Reiser G., Keep R. F., 2003. The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective? J. Neurochem. 84, 3-9.
  • Xie W. Z., Leibl M., Clark M. R., Dohrmann P., Kunze T., Gieseler F., 2005. Activation of the coagulation system in cancerogenesis and metastasation. Biomed. Pharmacother. 59, 70-75.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-ksv61p445kz
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