Department of Pharmacology, Osaka University Graduate School of Dentistry, Suita, 565-0871, Japan; The Institute of Prophylactic Pharmacology, Kita-Shinagawa, Shinagawa, 140-0001, Tokyo, Japan.
The Institute of Prophylactic Pharmacology, Kita-Shinagawa, Shinagawa, 140-0001, Tokyo, Japan; Laboratory of Molecular Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Hirakata, 573-0101, Japan.
Neurochem Int. 2019 Oct;129:104505. doi: 10.1016/j.neuint.2019.104505. Epub 2019 Jul 13.
The green tea amino acid theanine is abundant in green tea rather than black and oolong teas, which are all made of the identical tea plant "Chanoki" (Camellia sinensis). Theanine has a molecular structure close to glutamine (GLN) compared to glutamic acid (Glu), in terms of the absence of a free carboxylic acid moiety from the gamma carbon position. Theanine efficiently inhibits [H]GLN uptake without affecting [H]Glu uptake in rat brain synaptosomes. In contrast to GLN, however, theanine markedly stimulates the abilities to replicate and to commit to a neuronal lineage following prolonged exposure in cultured neural progenitor cells (NPCs) prepared from embryonic and adult rodent brains. Upregulation of transcript expression is found for one of the GLN transporter isoforms, Slc38a1, besides the promotion of both proliferation and neuronal commitment along with acceleration of the phosphorylation of mechanistic target of rapamycin (mTOR) and relevant downstream proteins, in murine NPCs cultured with theanine. Stable overexpression of Slc38a1 similarly facilitates both cellular replication and neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells with stable overexpression of Slc38a1, marked phosphorylation is seen for mTOR and downstream proteins in a manner insensitive to further additional phosphorylation by theanine. Taken together, theanine would exhibit a novel pharmacological property to up-regulate Slc38a1 expression for activation of the intracellular mTOR signaling pathway required for neurogenesis after sustained exposure in undifferentiated NPCs in the brain. In this review, a novel neurogenic property of the green tea amino acid theanine is summarized for embryonic and adult neurogenesis with a focus on the endogenous amino acid GLN on the basis of our accumulating evidence to date.
绿茶中的氨基酸茶氨酸含量丰富，而黑茶和乌龙茶则不然，它们均由同一茶树“茶树”（Camellia sinensis）制成。与谷氨酸（Glu）相比，茶氨酸在γ位上没有游离的羧基部分，其分子结构与谷氨酰胺（GLN）接近。茶氨酸可有效抑制大鼠脑突触体摄取[H]GLN，而不影响[H]Glu 的摄取。然而，与 GLN 不同的是，茶氨酸在培养的神经祖细胞（NPC）中，经长期暴露后，能显著刺激 NPC 增殖和向神经元谱系分化的能力，这些 NPC 是从小鼠胚胎和成年大脑中制备的。在含茶氨酸的培养物中，除了促进增殖和神经元分化以及加速雷帕霉素（mTOR）及其相关下游蛋白的磷酸化外，还发现一种 GLN 转运体同工型 Slc38a1 的转录表达上调。在含茶氨酸的培养物中，Slc38a1 的稳定过表达同样促进了多能胚胎癌细胞 P19 的细胞复制和神经元分化。在稳定过表达 Slc38a1 的 P19 细胞中，mTOR 和下游蛋白的磷酸化明显，且对茶氨酸进一步的额外磷酸化不敏感。综上所述，茶氨酸在未分化的 NPC 中持续暴露后，通过上调 Slc38a1 表达来激活细胞内 mTOR 信号通路，从而表现出一种新的药理学特性，这对于神经发生具有重要意义。在本文综述中，我们根据目前积累的证据，重点关注内源性氨基酸 GLN，总结了绿茶氨基酸茶氨酸在胚胎和成年神经发生中的新的神经发生特性。
