Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication
Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication
复制标题
DOI：
10.1016/j.abb.2004.11.002
复制
发表时间：
2005-02-15
影响因子：
3.9
通讯作者：
Klotz, LO
中科院分区：
文献类型：
--
作者：
Abdelmohsen, K;Stuhlmann, D;Klotz, LO
Dicumarol [3，3 '-亚甲基-双（4-羟基香豆素）]是NAD（P）H：醌氧化还原酶-1的有效抑制剂。大鼠肝上皮细胞或人皮肤成纤维细胞暴露于双香豆素导致连接蛋白-43依赖的间隙连接细胞间通讯（GJC）的快速和完全抑制。去除双香豆素后60分钟内GJC恢复。GJC的半数最大抑制所需的双香豆素浓度为3 μ M。使得双香豆素在阻断GJC方面比已知的GJC抑制剂1-辛醇和氟灭酸有效约10倍。Warcantine，一种相关的香豆素衍生物，也减弱了GJC，但需要5-10 mM的非常高的浓度。没有发现双香豆素诱导的GJC下调（这是由于干扰了增强连接蛋白-43磷酸化的途径）。如表皮生长因子受体和细胞外信号调节激酶途径。当然。双香豆素对GJC抑制作用被连接蛋白-43的磷酸化形式（“P2”）的可逆损失所抵消。(C)2004爱思唯尔公司All rights reserved.
Dicumarol [3,3'-methylene-bis(4-hydroxycoumarin)] is a potent inhibitor of NAD(P)H:quinone oxidoreductase-1. Exposure of rat liver epithelial cells or Of human skin fibroblasts to dicumarol resulted in a rapid and complete inhibition of connexin-43-dependent gap junctional intercellular communication (GJC). GJC was restored within 60 min following removal of dicumarol. The concentration of dicumarol required for half maximal inhibition of GJC was 3 muM. making dicumarol about 10-fold more effective in blocking GJC than 1-octanol and flufenamic acid, known inhibitors of GJC. Warfarin, a related coumarin derivative, also attenuated GJC, yet very high concentrations of 5-10 mM were required. Dicumarol-induced downregulation of GJC was found no( to be due to an interference with pathways enhancing the phosphorylation of connexin-43. such as epidermal growth factor receptor and extracellular signal-regulated kinase pathways. Rather. inhibition of GJC by dicumarol was paralleled by a reversible loss of a phosphorylated form ("P2") of connexin-43. (C) 2004 Elsevier Inc. All rights reserved.