Inhibition of gap junction communication in alveolar epithelial cells by 18α-glycyrrhetinic acid
Inhibition of gap junction communication in alveolar epithelial cells by 18α-glycyrrhetinic acid
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DOI：
10.1152/ajplung.1999.276.6.l1018
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发表时间：
1999-06-01
影响因子：
4.9
通讯作者：
Rannels, DE
中科院分区：
文献类型：
--
作者：
Guo, YH;Martinez-Williams, C;Rannels, DE
培养的肺泡上皮细胞具有缝隙连接细胞间通讯(GJIC)功能，并表达受调控水平的连接蛋白(CX)43mRNA和蛋白。新合成的放射性标记的Cx43蛋白与磷酸化的Cx43亚型保持平衡；这些物种聚集在一起形成连接蛋白和功能缝隙连接斑块。皂苷18α-甘草次酸(GA)在低浓度(5亩M)下快速、可逆地使GJIC变黑。长期暴露于较高浓度的18α-GA会抑制GJIC，并导致Cx43蛋白和mRNA表达的时间和剂量依赖性减少。后者的毒性作用与缝隙连接斑块的分解平行，并且不像对GJIC的急性作用那样容易逆转。这些观察证实了18α-GA对哺乳动物肺上皮细胞间通讯的敏感调节，并提示Cx43的表达和磷酸化在肺泡上皮细胞间GJIC的急性和慢性调节中起作用。
Cultured alveolar epithelial cells exhibit gap junction intercellular communication (GJIC) and express regulated levels of connexin (Cx) 43 mRNA and protein. Newly synthesized radiolabeled Cx43 protein equilibrates with phosphorylated Cx43 isoforms; these species assemble to form both connexons and functional gap junction plaques. The saponin 18 alpha-glycyrrhetinic acid (GA) rapidly and reversibly blacks GJIC at low concentrations (5 mu M). Extended exposure to 18 alpha-GA at higher concentrations causes inhibition of GJIC and time- and dose-dependent reductions in both Cx43 protein and mRNA expression. The latter toxic effects are paralleled by disassembly of gap junction plaques and are reversed less readily than acute effects on GJIC. These observations demonstrate 18 alpha-GA-sensitive regulation of intercellular communication in epithelial cells from the mammalian lung and suggest a role for Cx43 expression and phosphorylation in acute and chronic regulation of GJIC between alveolar epithelial cells.