Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein phosphatase 2A
Sealing effects of (-)-epigallocatechin gallate on protein kinase C and protein phosphatase 2A
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DOI：
10.1016/s0301-4622(96)02254-5
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发表时间：
1997-04-22
影响因子：
3.8
通讯作者：
Imanishi, Y
中科院分区：
文献类型：
--
作者：
Kitano, K;Nam, KY;Imanishi, Y
表没食子儿茶素没食子酸酯(EGCG)能抑制12-O-十四酰佛波醇-13-乙酸酯(TPA)对蛋白激酶C(PKC)的激活，抑制肿瘤促进剂与其受体的相互作用，被称为“封闭效应”。为了阐明EGCG的封闭作用，我们制备了脂质体，考察了分散在脂质体中的不同浓度的EGCG对PKC活化的抑制作用。添加到脂质体分散体中的EGCG要么以聚集体形式存在于缓冲溶液中，要么存在于磷脂双层膜中，并且EGCG扰乱了膜的结构。EGCG对PKC活性的抑制作用与脂质体的性质有关，说明EGCG与磷脂双层膜的相互作用影响PKC的激活。此外，EGCG还可阻止腺苷5‘-三磷酸和TPA与PKC的结合，从而抑制PKC的激活。而蛋白磷酸酶2A(PP？A)的活性在脂质体存在下受到抑制，但不受EGCG的影响。此外，EGCG在缓冲溶液中恢复了PP2A的磷酸酶活性，该酶的活性被冈田酸抑制。以上结果表明，EGCG通过抑制多种配体与蛋白质的相互作用，对PKC和PP2A具有封闭作用。(C)1997年爱思唯尔科学公司。
(-)-Epigallocatechin gallate (EGCG) was reported to inhibit protein kinase C (PKC) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA), and inhibit interaction of tumor promoter with its receptors, named 'a sealing effect'. In order to clarify the sealing effect of EGCG, we prepared Liposomes and examined inhibition of PKC activation by various concentrations of EGCG dispersed in the liposome. EGCG added to a liposome dispersion existed either in a buffer solution as aggregates or in phospholipid bilayer membranes, and EGCG disturbed membrane structure. The potency of inhibitory effect of EGCG on PKC activation was dependent on the nature of Liposomes, indicating that interaction of EGCG with phospholipid bilayer membrane affects PKC activation. Moreover, EGCG prevented the binding of adenosine 5'-triphosphate and TPA to PKC, resulting in inhibition of PKC activation. On the other hand, the activity of protein phosphatase 2A (PP?A) was suppressed in the presence of liposomes, but was not influenced by EGCG. Moreover, EGCG recovered phosphatase activity of PP2A in a buffer solution, the activity of which was inhibited by okadaic acid. All the results indicated that EGCG possesses sealing effects in terms of PKC and PP2A, by inhibiting interaction of various ligands with proteins. (C) 1997 Elsevier Science B.V.