The PI3K/Akt pathway is present and functional in the preimplantation mouse embryo
The PI3K/Akt pathway is present and functional in the preimplantation mouse embryo
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DOI：
10.1016/j.ydbio.2005.05.033
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发表时间：
2005-08-15
影响因子：
2.7
通讯作者：
Moley, KH
中科院分区：
文献类型：
--
作者：
Riley, JK;Carayannopoulos, MO;Moley, KH
PI3KJAkt 信号转导途径是众所周知的生长促进和细胞存活信号的介质。虽然该通路的表达和功能已在生殖过程的早期和晚期阶段得到记录，但目前没有证据表明 PI3K/Akt 通路在小鼠植入前胚胎中的存在或功能。我们使用共聚焦免疫荧光显微镜和蛋白质印迹分析发现，PI3K 和 Akt 的 p85 和 p110 亚基在小鼠植入前胚胎发育的囊胚阶段从 1 细胞表达。从 1 细胞到桑葚胚阶段，这些蛋白质主要定位于细胞表面。在囊胚阶段，PI3K 和 Akt 在滋养外胚层细胞中均表现出顶端染色模式。有趣的是，在小鼠植入前发育过程中检测到磷酸化 Akt，其在质膜上的存在反映了其激活状态。 Akt 活性的抑制对囊胚的正常生理有显着影响。具体来说，抑制该途径会导致胰岛素刺激的葡萄糖摄取减少。此外，抑制 Akt 活性会导致囊胚孵化显着延迟，这是促进植入的发育步骤。最后，我们确定了滋养层干（TS）细胞中存在该通路，这是研究该信号级联的潜在有用的体外模型。总而言之，这些数据首次证明了哺乳动物植入前胚胎中 PI3K/Akt 通路的存在和功能。 (c) 2005 Elsevier Inc. 保留所有权利。
The PI3KJAkt signal transduction pathway is a well-known mediator of growth promoting and cell survival signals. While the expression and function of this pathway have been documented during early and late stages of the reproductive process, currently, there is no evidence demonstrating either the presence or function of the PI3K/Akt pathway in murine preimplantation embryos. We found, using confocal immunofluorescent microscopy and Western blot analysis, that the p85 and p110 subunits of PI3K and Akt are expressed from the 1-cell through the blastoeyst stage of murine preimplantation embryo development. These proteins were localized predominantly at the cell surface from the 1-cell through the morula stage. At a blastocyst stage, both PI3K and Akt exhibited an apical staining pattern in the trophectoderm cells. Interestingly, phosphorylated Akt was detected throughout murine preimplantation development, and its presence at the plasma membrane is a reflection of its activation status. Inhibition of Akt activity had significant effects on the normal physiology of the blastocyst. Specifically, inhibition of this pathway resulted in a reduction in insulin-stimulated glucose uptake. In addition, inhibiting Akt activity resulted in a significant delay in blastocyst hatching, a developmental step facilitating implantation. Finally, we established the presence of this pathway in trophoblast stem (TS) cells, a potentially useful in vitro model to study this signaling cascade. Taken together, these data are the first to demonstrate the presence and function of the PI3K/Akt pathway in mammalian preimplantation embryos. (c) 2005 Elsevier Inc. All rights reserved.