Oxytocin modulates mTORC1 pathway in the gut.
Oxytocin modulates mTORC1 pathway in the gut.
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DOI：
10.1016/j.bbrc.2013.01.121
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发表时间：
2013-03-15
影响因子：
3.1
通讯作者：
Welch, Martha G.
中科院分区：
文献类型：
--
作者：
Klein, Benjamin Y.;Tamir, Hadassah;Hirschberg, David L.;Glickstein, Sara B.;Welch, Martha G.
我们最近发现，催产素(OT)及其受体(OTR)在大鼠肠道神经系统和绒毛-隐窝肠道细胞中的表达模式与断奶相关，再加上已知的母乳中催产素的高水平和稳定性，支持催产素可能在肠道功能和发育中发挥作用。我们先前在OT处理的肠道细胞中描述了PI3K/Akt通路的两相剂量-反应。激活在62.5 nM OT(30min)时达到峰值，并与OTR内化相一致。在这里，我们使用自动Western blotting进一步探索OT诱导的Akt和pAktT308以及下游底物p70 S6激酶-1(S6K1)和eIF-4E结合蛋白1(4E-BP1)的变化。与单独的新鲜生长介质(FGM)相比，我们的结果表明，FGM中的OT降低了哺乳动物雷帕霉素复合体1(MTORC1)的底物S6K1的丰度和磷酸化，以及4E-BP1的磷酸化。高浓度和低浓度的OT均可促进mTORC1调节因子RaptorS792的磷酸化，并预测其对mTORC1的抑制作用。因此，OT下调由mTORC1催化的FGM活性所引起的合成代谢效应。OT是Caco 2BB细胞中PI3K/Akt/mTORC1通路的调节者，可能调节肠道细胞的翻译。
Our recent findings of a weaning-related pattern of oxytocin (OT) and OT receptor (OTR) expression in the rat enteric nervous system and in villus-crypt enterocytes, together with the known high level and stability of OT in breast milk support that OT may play a role in gut function and development. We previously described a biphasic dose- response of the PI3K/Akt pathway in gut cells treated with OT. Activation peaked at 62.5 nM OT (30 min) and coincided with OTR internalization. Here we use automated Western blotting to further explore OT-elicited changes in Akt and pAktT308, as well as in downstream substrates p70 S6 kinase-1 (S6K1) and eIF-4E binding protein 1 (4E-BP1). Relative to fresh growth medium (FGM) alone, our results showed OT in FGM reduced the abundance and phosphorylation of S6K1 and the phosphorylation of 4E-BP1, both substrates of mammalian target of rapamycin complex 1 (mTORC1). Phosphorylation of mTORC1 regulator, RaptorS792, was increased by high and low OT concentrations, with predicted inhibitory effects on mTORC1. OT thus downregulates anabolic effects induced by FGM activity catalyzed by mTORC1. OT is a regulator of the PI3K/Akt/mTORC1 pathway in Caco2BB cells and may modulate translation in gut cells.
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
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