Possible activation by the green tea amino acid theanine of mammalian target of rapamycin signaling in undifferentiated neural progenitor cells in vitro.
Possible activation by the green tea amino acid theanine of mammalian target of rapamycin signaling in undifferentiated neural progenitor cells in vitro.
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DOI：
10.1016/j.bbrep.2015.09.021
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发表时间：
2016-03
影响因子：
2.7
通讯作者：
Yoneda Y
中科院分区：
文献类型：
--
作者：
Takarada T;Nakamichi N;Nakazato R;Kakuda T;Kokubo H;Ikeno S;Nakamura S;Kuramoto N;Hinoi E;Yoneda Y
我们已经显示出显着的促进增殖和神经元分化的多能性P19细胞暴露于绿色茶氨基酸茶氨酸，这是一个很好的基板SLC 38 A1负责谷氨酰胺运输。在这项研究中，我们评估了活性的哺乳动物雷帕霉素（mTOR）激酶通路，参与蛋白质翻译，细胞生长和自噬的方式相关的细胞内谷氨酰胺水平，在小鼠神经祖细胞暴露于茶氨酸。暴露于茶氨酸促进胚胎小鼠新皮质神经球中mTOR和下游蛋白的磷酸化。虽然稳定的SLC 38 A1过表达同样促进了未分化的P19细胞中mTOR相关蛋白的磷酸化，但茶氨酸未能额外加速这些稳定转染子中磷酸化的增加。茶氨酸促进小鼠胚胎新皮层和成年海马神经球的形成，沿着促进胚胎神经球中5-溴-2 '-脱氧尿苷掺入和3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2H-溴化四氮唑还原。在胚胎神经球以前暴露于茶氨酸，一个显着增加的细胞数量的神经元标记蛋白的免疫反应后自发分化。这些结果表明，茶氨酸激活mTOR信号通路以促进小鼠未分化神经祖细胞的增殖并加速神经发生。茶氨酸促进神经祖细胞中的mTOR磷酸化。茶氨酸促进胚胎和成人神经球的形成。SLC 38 A1过表达促进多能P19细胞中mTOR磷酸化茶氨酸不能进一步促进SLC 38 A1转染子中的mTOR磷酸化。茶氨酸促进胚胎祖细胞随后的神经元分化。
We have shown marked promotion of both proliferation and neuronal differentiation in pluripotent P19 cells exposed to the green tea amino acid theanine, which is a good substrate for SLC38A1 responsible for glutamine transport. In this study, we evaluated the activity of the mammalian target of rapamycin (mTOR) kinase pathway, which participates in protein translation, cell growth and autophagy in a manner relevant to intracellular glutamine levels, in murine neural progenitor cells exposed to theanine. Exposure to theanine promoted the phosphorylation of mTOR and downstream proteins in neurospheres from embryonic mouse neocortex. Although stable overexpression of SLC38A1 similarly facilitated phosphorylation of mTOR-relevant proteins in undifferentiated P19 cells, theanine failed to additionally accelerate the increased phosphorylation in these stable transfectants. Theanine accelerated the formation of neurospheres from murine embryonic neocortex and adult hippocampus, along with facilitation of both 5-bromo-2’-deoxyuridine incorporation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction in embryonic neurospheres. In embryonic neurospheres previously exposed to theanine, a significant increase was seen in the number of cells immunoreactive for a neuronal marker protein after spontaneous differentiation. These results suggest that theanine activates the mTOR signaling pathway for proliferation together with accelerated neurogenesis in murine undifferentiated neural progenitor cells. Theanine promotes mTOR phosphorylation in neural progenitors. Theanine promotes the formation of embryonic and adult neurospheres. SLC38A1 overexpression promotes mTOR phosphorylation in pluripotent P19 cells. Theanine fails to further promote mTOR phosphorylation in SLC38A1 transfectants. Theanine promotes subsequent neuronal differentiation in embryonic progenitors.