Naomoto Yoshio, Yamatsuji Tomoki, Shigemitsu Kaori, Ban Hidetoshi, Nakajo Tohru, Shirakawa Yasuhiro, Motok Takayuki, Kobayashi Masahiko, Gunduz Mehmet, Tanaka Noriaki
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1, Okayama 700-8558, Japan.
Int J Mol Med. 2005 Aug;16(2):201-4.
There is much interest in precise functions of amino acids on mammalian growth and development. Some of amino acids play important roles in the control of gene expression by controlling the initiation phase of mRNA translation. The signal induced by leucine or arginine may stimulate cell growth. On the other hand, the other signal induced by glutamine may stimulate cellular proliferation and increase cell number, but inhibit the growth of cell size. However, there was no clear evidence that an individual amino acid specifically works as a signaling molecule. In our recent study, not only leucine, but also arginine is shown to activate the mTOR signaling pathway in rat intestinal epithelial cells. Furthermore, regarding L-Glutamine, an important amino acid that is required for culturing of numerous cell types, including rat intestinal epithelial cells, we have shown that it had an inhibitory effect on leucine- or arginine-induced activation of the mTOR signaling pathway. We have demonstrated that L-Glutamine inhibited the activation of p70 S6 kinase and phosphorylation of 4E-BP1 induced by arginine or leucine in rat intestinal epithelial cells. Based on these results, we are planning to confirm the effect of each amino acid including glutamine in an in vivo model using new born mice.
氨基酸对哺乳动物生长发育的精确功能备受关注。一些氨基酸通过控制mRNA翻译的起始阶段在基因表达调控中发挥重要作用。亮氨酸或精氨酸诱导的信号可能刺激细胞生长。另一方面，谷氨酰胺诱导的另一种信号可能刺激细胞增殖并增加细胞数量，但会抑制细胞大小的增长。然而，尚无明确证据表明单个氨基酸可作为特异性信号分子发挥作用。在我们最近的研究中，不仅亮氨酸，而且精氨酸也被证明可激活大鼠肠上皮细胞中的mTOR信号通路。此外，关于L-谷氨酰胺，这是包括大鼠肠上皮细胞在内的多种细胞类型培养所需的一种重要氨基酸，我们已经表明它对亮氨酸或精氨酸诱导的mTOR信号通路激活具有抑制作用。我们已经证明，L-谷氨酰胺在大鼠肠上皮细胞中可抑制精氨酸或亮氨酸诱导的p70 S6激酶激活和4E-BP1磷酸化。基于这些结果，我们计划使用新生小鼠在体内模型中确认包括谷氨酰胺在内的每种氨基酸的作用。
