The involvement of the 67 kDa laminin receptor-mediated modulation of cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O-gallate
The involvement of the 67 kDa laminin receptor-mediated modulation of cytoskeleton in the degranulation inhibition induced by epigallocatechin-3-O-gallate
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DOI：
10.1016/j.bbrc.2006.07.086
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发表时间：
2006-09-22
影响因子：
3.1
通讯作者：
Tachibana, Hirofumi
中科院分区：
文献类型：
--
作者：
Fujimura, Yoshinori;Umeda, Daisuke;Tachibana, Hirofumi
最近，我们报道了 (-)-表没食子儿茶素-3-O-没食子酸酯 (EGCG) 作为脱粒抑制剂。然而，脱粒的抑制机制仍然知之甚少。在这里，我们发现，EGCG 对钙离子载体诱导的人嗜碱性 KU812 细胞脱颗粒的抑制作用涉及胞吐作用相关的肌球蛋白 II 调节轻链磷酸化和肌动蛋白重塑的改变。表面等离子共振测定还表明，EGCG 与细胞表面结合，脂筏的破坏导致 EGCG 的能力降低。我们之前已经将筏相关的 67 kDa 层粘连蛋白受体 (67LR) 鉴定为细胞表面的 EGCG 受体。用抗67LR抗体处理细胞或RNA干扰介导的67LR表达下调消除了EGCG的作用。这些发现表明，EGCG 诱导的脱颗粒抑制包括 EGCG 与细胞表面 67LR 的初步结合以及随后的细胞骨架调节。 (c) 2006 Elsevier Inc. 保留所有权利。
Recently, we have reported that (-)-epigallocatechin-3-O-gallate (EGCG) acts as an inhibitor of degranulation. However, the inhibitory mechanism for degranulation is still poorly understood. Here we show that suppression of exocytosis-related myosin II regulatory light chain phosphorylation and alteration of actin remodeling are involved in the inhibitory effect of EGCG on the calcium ionophore-induced degranulation from human basophilic KU812 cells. Surface plasmon resonance assay also revealed that EGCG binds to the cell surface, and the disruption of lipid rafts resulted in reduction of EGCG's ability. We have previously identified the raft-associated 67 kDa laminin receptor (67LR) as an EGCG receptor on the cell surface. Treatment of the cells with anti-67LR antibody or RNA interference-mediated downregulation of 67LR expression abolished the effects of EGCG. These findings suggest that EGCG-induced inhibition of the degranulation includes the primary binding of EGCG to the cell surface 67LR and subsequent modulation of cytoskeleton. (c) 2006 Elsevier Inc. All rights reserved.