ANTICOAGULANT ACTIVITY OF A HEPARIN FROM ASCIDIAN
Transcrição
ANTICOAGULANT ACTIVITY OF A HEPARIN FROM ASCIDIAN
ANTICOAGULANT ACTIVITY OF A HEPARIN FROM ASCIDIAN PHALLUSIA NIGRA (CHORDATA: TUNICATA) Christiane F. Sobral, Eliene O. Kozlowski and Mauro S. G. Pavão from Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica, UFRJ Heparin is a well-known glycosaminoglycan for its ability to prevent blood coagulation. Although heparin from mammalian origin is clinically used as an anticoagulant drug, the appearance of bovine prion diseases and the haemorragic effect of high doses of heparin have limited its use. Therefore to look for new sources of heparin-like compounds is an important goal of glycobiologists. In this work, a heparin-like glycan was extracted from ascidian Phallusia nigra and purified using anion-exchange chromatography on a DEAE-cellulose and MONOQ/FPLC columns. The ascidian heparin has a low molecular weight glycan (~12 KDa), as determined by PAGE in barbital buffer. The anticoagulant activity was meansured by the aPTT assay, in which it showed a ~60-fold lower anticoagulant activity (3 units/mg) then bovine heparin (180 units/mg). Ascidian heparin is able to inhibit factor Xa via antithrombin (IC 50 = 3.14 µg/mL), but thrombin inhibition was very lower (IC 50 = 0.74 µg/mL), as comparing with mammalian heparin (IC 50 = 0.143 µg/mL and IC 50 = 0.90 ng/mL, respectively). Taken together, these results point to a selective activity of the ascidian heparin as a factor Xa inhibitor. A detailed study about the structure of this heparin is being performed to establish a correlation among the low molecular weight, structural features and anticoagulant activity. Key words: ascidian, anticoagulant, glycosaminoglycan, heparin Financial support: CAPES, CNPq, FAPERJ, NIH-FIC (R03TW05775)
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