A noble function of BAY 11-7082: Inhibition of platelet aggregation mediated by an elevated cAMP-induced VASP, and decreased ERK2/JNK1 phosphorylations

European Journal of Pharmacology
Hyun-Sub LeeMan-Hee Rhee

Abstract

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 ...Continue Reading

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Citations

Jul 23, 2013·Vascular Pharmacology·Sordar Mohammed KamruzzamanMan Hee Rhee
Aug 18, 2012·Evidence-based Complementary and Alternative Medicine : ECAM·Ji Young ParkMan Hee Rhee
Mar 8, 2016·European Journal of Pharmacology·Qian HongYue Gao
Sep 3, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Ji Young ParkMan Hee Rhee
Mar 13, 2015·Frontiers in Immunology·Katie L LannanRichard P Phipps
Feb 22, 2017·Frontiers in Immunology·Pauline DamienHind Hamzeh-Cognasse
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Feb 15, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Dong-Seon KimHo Kyoung Kim
May 18, 2020·Chinese Journal of Integrative Medicine·Abdullah S ShatoorMahmoud Alkhateeb
Aug 30, 2019·International Journal of Molecular Sciences·Kevin KojokYahye Merhi
Feb 20, 2019·Frontiers in Immunology·Marion MussbacherJohannes A Schmid
May 1, 2021·International Journal of Molecular Sciences·Abed El-Hakim El-Kadiry, Yahye Merhi
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