Lee, H.S. et al. A noble function of BAY 11-7082: inhibition of platelet aggregation mediated by an elevated cAMP-induced VASP, and decreased ERK2/JNK1 phosphorylations. Eur. J. Pharmacol. 627, 85-91

College of Biomedical Science and Engineering, and Regional Research Center, Inje University, Gimhae 200-701, Republic of Korea.
European journal of pharmacology (Impact Factor: 2.53). 11/2009; 627(1-3):85-91. DOI: 10.1016/j.ejphar.2009.11.005
Source: PubMed


Platelets, though anucleated, possess several transcription factors, including NF-kappaB, that exert non-genomic functions regulating platelet activation. Since platelets have not only been recognized as central players of homeostasis, but also participated in pathological conditions such as thrombosis, atherosclerosis, and inflammation, we examined rat platelet NF-kappaB expression and evaluated the effects of anti-inflammatory drug BAY 11-7082, an inhibitor of NF-kappaB activation, in platelet physiology. Western blotting revealed that rat platelets express NF-kappaB. BAY 11-7082, dose dependently, inhibited collagen- or thrombin-induced-platelet aggregation. ATP release, TXB(2) formation, P-selectin expression, and intercellular Ca(2+) concentration activated by collagen were reduced in BAY 11-7082-treated platelets. BAY 11-7082 elevated intracellular levels of cAMP, but not cGMP, and its co-incubation with cAMP-activating agent (forskolin) or its hydrolyzing enzyme inhibitor (3-isobutyl-1-methylxanthine, IBMX), synergistically inhibited collagen-induced-platelet aggregation. In addition, vasodilator-stimulated-phosphoprotein (VASP) phosphorylation was enhanced in BAY 11-7082-treated platelets, which was partially inhibited by a protein kinase A (PKA) inhibitor, H-89. Moreover, while p38 mitogen-activated protein kinase (MAPK) was not affected, BAY 11-7082 attenuated c-Jun N-terminal kinase 1 (JNK1) and extracellular-signal-regulated protein kinase 2 (ERK2) phosphorylations. In conclusion, BAY 11-7082 inhibits platelet activation, granule secretion, and aggregation, and that this effect is mediated by inhibition of JNK1 and ERK2 phosphorylations, and partially by stimulation of cAMP-dependent PKA VASP phosphorylation. The ability of BAY 11-7082 to inhibit platelet function might be relevant in cases involving aberrant platelet activation where the drug is considered as anti-atherothrombosis, and anti-inflammatory therapy.

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    Evidence-based Complementary and Alternative Medicine 02/2014; 2014:639548. DOI:10.1155/2014/639548 · 1.88 Impact Factor
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    • "The amount of intracellular calcium ([Ca 2+ ]i) was determined with fura-2/AM as described previously [20]. Briefly, the platelet-rich plasma was incubated with 5 μM of fura-2/AM for 60 min at 37 °C. "
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    Vascular Pharmacology 07/2013; DOI:10.1016/j.vph.2013.07.002 · 3.64 Impact Factor
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    • "Interestingly, quercetin-mediated attenuation of P-selectin expression and MAP kinase activation in this study suggests that the antiplatelet activity of the compound could be linked to its regulation of hemostatic- and inflammatory responses. Since platelets are involved in inflammation, P-selectin expression on the membrane of activated platelets is the main link between platelets and inflammatory cells [7, 45] and quercetin-mediated suppression of P-selectin expression and MAPKs activation in this paper may be attributed to its anti-inflammatory property. "
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