%0 Journal Article
%T A novel role of sesamol in inhibiting NF-百B-mediated signaling in platelet activation
%A Chao-Chien Chang
%A Wan-Jung Lu
%A Eng-Thiam Ong
%A Cheng-Wen Chiang
%A Song-Chow Lin
%A Shih-Yi Huang
%A Joen-Rong Sheu
%J Journal of Biomedical Science
%D 2011
%I BioMed Central
%R 10.1186/1423-0127-18-93
%X Platelet aggregation, Fura 2-AM fluorescence, and immunoblotting analysis were used in this study.NF-百B signaling events, including IKK汕 phosphorylation, I百B汐 degradation, and p65 phosphorylation, were markedly activated by collagen (1 米g/ml) in washed human platelets, and these signaling events were attenuated by sesamol (2.5~25 米M). Furthermore, SQ22536 and ODQ, inhibitors of adenylate cyclase and guanylate cyclase, respectively, strongly reversed the sesamol (25 米M)-mediated inhibitory effects of IKK汕 phosphorylation, I百B汐 degradation, and p65 phosphorylation stimulated by collagen. The protein kinase A (PKA) inhibitor, H89, also reversed sesamol-mediated inhibition of I百B汐 degradation. Moreover, BAY11-7082, an NF-百B inhibitor, abolished I百B汐 degradation, phospholipase C (PLC)污2 phosphorylation, protein kinase C (PKC) activation, [Ca2+]i mobilization, and platelet aggregation stimulated by collagen. Preincubation of platelets with the inhibitors, SQ22536 and H89, both strongly reversed sesamol-mediated inhibition of platelet aggregation and [Ca2+]i mobilization.Sesamol activates cAMP-PKA signaling, followed by inhibition of the NF-百B-PLC-PKC cascade, thereby leading to inhibition of [Ca2+]i mobilization and platelet aggregation. Because platelet activation is not only linked to hemostasis, but also has a relevant role in inflammation and metastasis, our data demonstrating that inhibition of NF-百B interferes with platelet function may have a great impact when these types of drugs are considered for the treatment of cancer and various inflammatory diseases.Sesamol (3,4-methylenedioxyphenol) is a constituent of roasted sesame seeds, Sesamum indicum L., an important oilseed crop [1]. Sesamol is a potent phenolic antioxidant contained only in processed sesame oil. Several beneficial effects of sesamol were reported including antioxidation, chemoprevention, antimutagenic, and antihepatotoxic properties [2-5]. Traditionally, sesame seed oil was used to remove wrinkles a
%K I百B汐
%K IKK
%K intracellular Ca2+
%K protein kinase A
%K platelet activation
%K sesamol
%U http://www.jbiomedsci.com/content/18/1/93