Long-term Forskolin Stimulation Induces AMPK Activation and Thereby Enhances Tight junction Formation in Human Placental Trophoblast BeWo Cells
Long-term Forskolin Stimulation Induces AMPK Activation and Thereby Enhances Tight junction Formation in Human Placental Trophoblast BeWo Cells
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DOI：
10.1016/j.placenta.2008.09.008
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发表时间：
2008-12-01
期刊：
影响因子：
3.8
通讯作者：
Asano, T.
中科院分区：
文献类型：
--
作者：
Egawa, M.;Kamata, H.;Asano, T.
已知来源于人绒毛膜癌的BeWo细胞通过在人胎盘的绒毛膜绒毛表面上分化成多核细胞样合胞体滋养层而对毛喉素或cAMP类似物作出反应。在这项研究中，我们证明，长期治疗与毛喉素增强紧密连接（TJ）在人类胎盘BeWo细胞的形成。有趣的是，AMPK激活和乙酰辅酶A羧化酶（ACC）的磷酸化，AMPK下游的分子，诱导长期孵育（> 12小时）与毛喉素，尽管没有诱导急性刺激与毛喉素。此外，与AMPK抑制剂化合物C共孵育以及AMPK显性失活突变体的过表达抑制毛喉素诱导的TJ形成。因此，尽管通过毛喉素刺激激活AMPK的分子机制尚不清楚，但毛喉素诱导的TJ形成可能是由AMPK途径介导的。考虑到TJ存在于正常人胎盘中，这种机制可能对形成胎儿和母体循环之间的胎盘屏障系统很重要。(c)2008爱思唯尔有限公司保留所有权利。
BeWo cells, derived from human choriocarcinoma, have been known to respond to forskolin or cAMP analogues by differentiating into multinucleated cells- like syncytiotrophoblasts on the surfaces of chorionic villi of the human placenta. In this study, we demonstrated that long-term treatment with forskolin enhances the tight junction (TJ) formation in human placental BeWo cells. Interestingly, AMPK activation and phosphorylation of acetyl-CoA carboxylase (ACC), a molecule downstream from AMPK, were induced by long-term incubation (> 12 h) with forskolin, despite not being induced by acute stimulation with forskolin. In addition, co-incubation with an AMPK inhibitor, compound C, as well as overexpression of an AMPK dominant negative Mutant inhibited forskolin-induced TJ formation. Thus, although the molecular mechanism underlying AMPK activation via the forskolin Stimulation is unclear, the TJ formation induced by forskolin is likely to be mediated by the AMPK pathway. Taking into consideration that TJs are present in the normal human placenta, this mechanism may be important for forming the placental barrier system between the fetal and maternal circulations. (c) 2008 Elsevier Ltd. All rights reserved.