The mechanism of anti-platelet activity of davallialactone: Involvement of intracellular calcium ions, extracellular signal-regulated kinase 2 and p38 mitogen-activated protein kinase

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Title
The mechanism of anti-platelet activity of davallialactone: Involvement of intracellular calcium ions, extracellular signal-regulated kinase 2 and p38 mitogen-activated protein kinase
Author(s)
S D Kim; In Kyoung Lee; W M Lee; J Y Cho; H J Park; J W Oh; S C Park; S K Kim; Y S Kwak; Bong Sik Yun; M H Rhee
Bibliographic Citation
European Journal of Pharmacology, vol. 584, no. 2, pp. 361-367
Publication Year
2008
Abstract
This study was designed to investigate the effect of davallialactone, which was isolated from the mushroom Inonotus xeranticus, on platelet aggregation induced by collagen, thrombin and ADP. We found that davallialactone dose-dependently inhibited platelet aggregation that was stimulated either by collagen (2.5 μg/ml), a potent ligand of integrin α2β1 and glycoprotein VI, or by thrombin (0.1U/ml), a potent agonist of the protease-activated receptors (PARs) PAR1 and PAR3. In addition, davallialactone inhibited platelet aggregation induced by ADP, an agonist of P2Y receptor. To understand the mechanism of anti-platelet activity, we determined whether davallialactone affected the downstream signaling in collagen-activated platelets. Using the fura-2/AM fluorometric assay, we found that davallialactone dose-dependently inhibited intracellular calcium concentration levels ([Ca2+]i). Moreover, davallialactone inhibited the phosphorylation of extracellular signal-regulated protein kinase (ERK)-2 and p38 mitogen-activated protein kinase (MAPK), in a dose-dependent manner. The tyrosine phosphorylation of 60 and 85kDa proteins, which were activated by collagen, were differentially inhibited by davallialactone. Taken together, these data suggest that davallialactone may have potential anti-platelet aggregation activity via suppression of intracellular downstream signaling pathways.
Keyword
[Ca2+]iADPcollagendavallialactoneERK2inonotus xeranticusp38 MAPKplatelet aggregationthrombin
ISSN
0014-2999
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ejphar.2008.02.008
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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