Lipid raft-associated catechin suppresses the FcεRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2

Lipid raft-associated catechin suppresses the FcεRI expression by inhibiting phosphorylation of the extracellular signal-regulated kinase1/2
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DOI:
10.1016/s0014-5793(03)01432-7
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发表时间:
2004-01-02
期刊:
影响因子:
3.5
通讯作者:
Yamada, K
Yamada, K
中科院分区:
生物学3区
文献类型:
--
作者:
Fujimura, Y;Tachibana, H;Yamada, K

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主要的绿茶儿茶素(-)-表没食子儿茶素没食子酸酯(EGCG)对高亲和力的IgE受体FcepsilonRI的表达具有抑制作用,FcepsilonRI是IgE介导的过敏反应中的关键分子。在这里,我们发现EGCG结合到细胞表面,并与人嗜碱性KU812细胞上的质膜微区、脂筏高度结合。这些脂筏的破坏导致与RAFT相关的EGCG的数量减少和EGCG的FcepsilonRI抑制作用。我们还发现,EGCG具有抑制细胞外信号调节蛋白1/2(ERK1/2)的磷酸化的能力,并且ERK1/2的特异性抑制剂也降低了FcepsilonRI的表达。此外,EGCG对ERK1/2的抑制作用可通过阻断RAFT而被阻断。因此,这些结果表明,EGCG与脂筏之间的相互作用对于EGCG下调FcepsilonRI表达的能力是重要的,ERK1/2可能参与了这一抑制信号。(C)2003年欧洲生化学会联合会。爱思唯尔出版,版权所有。
The major green tea catechin, (-)-epigallocatechin-3-O-gallate (EGCG), has a suppressive effect on the expression of the high-affinity IgE receptor FcepsilonRI, which is key molecule in the IgE-mediated allergic reactions. Here we show that EGCG binds to the cell surface and highly associates with plasma membrane microdomains, lipid rafts, on the human basophilic KU812 cells. The disruption of these lipid rafts caused a reduction of the amount of raft-associated EGCG and the FcepsilonRI-suppressive effect of EGCG. We also found that EGCG has an ability to inhibit the phosphorylation of the extracellular signal-regulated kinase1/2 (ERK1/2) and that the ERK1/2 specific inhibitor also reduced FcepsilonRI expression. Moreover, the inhibitory effect elicited by EGCG on ERK1/2 was prevented by disruption of rafts. Thus, these results suggest that the interaction between EGCG and the lipid rafts is important for EGCG's ability to downregulate FcepsilonRI expression, and ERK1/2 may be involved in this suppression signal. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.