Please use this identifier to cite or link to this item: doi:10.22028/D291-27444
Title: The Marine-Derived Kinase Inhibitor Fascaplysin Exerts Anti-Thrombotic Activity
Author(s): Ampofo, Emmanuel
Später, Thomas
Müller, Isabelle
Eichler, Hermann
Menger, Michael D.
Laschke, Matthias W.
Language: English
Title: Marine Drugs
Volume: 13
Issue: 11
Startpage: 6774
Endpage: 6791
Publisher/Platform: MDPI
Year of Publication: 2015
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Background: The marine-derived kinase inhibitor fascaplysin down-regulates the PI3K pathway in cancer cells. Since this pathway also plays an essential role in platelet signaling, we herein investigated the effect of fascaplysin on thrombosis. Methods: Fascaplysin effects on platelet activation, platelet aggregation and platelet-leukocyte aggregates (PLA) formation were analyzed by flow cytometry. Mouse dorsal skinfold chambers were used to determine <em>in vivo</em> the effect of fascaplysin on photochemically induced thrombus formation and tail-vein bleeding time. Results: Pre-treatment of platelets with fascaplysin reduced the activation of glycoprotein (GP)IIb/IIIa after protease-activated receptor-1-activating peptide (PAR-1-AP), adenosine diphosphate (ADP) and phorbol-12-myristate-13-acetate (PMA) stimulation, but did not markedly affect the expression of P-selectin. This was associated with a decreased platelet aggregation. Fascaplysin also decreased PLA formation after PMA but not PAR-1-AP and ADP stimulation. This may be explained by an increased expression of CD11b on leukocytes in PAR-1-AP- and ADP-treated whole blood. In the dorsal skinfold chamber model of photochemically induced thrombus formation, fascaplysin-treated mice revealed a significantly extended complete vessel occlusion time when compared to controls. Furthermore, fascaplysin increased the tail-vein bleeding time. Conclusion: Fascaplysin exerts anti-thrombotic activity, which represents a novel mode of action in the pleiotropic activity spectrum of this compound.
DOI of the first publication: 10.3390/md13116774
Link to this record: urn:nbn:de:bsz:291--ds-274447
hdl:20.500.11880/28538
http://dx.doi.org/10.22028/D291-27444
ISSN: 1660-3397
Date of registration: 6-Jan-2020
Faculty: M - Medizinische Fakultät
Department: M - Chirurgie
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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