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The role of PI3K/Akt/mTOR signaling in dose-dependent biphasic effects of glycine on vascular development
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| Title: | The role of PI3K/Akt/mTOR signaling in dose-dependent biphasic effects of glycine on vascular development |
| Authors: | Tsuji-Tamura, Kiyomi Browse this author →KAKEN DB | | Sato, Mari Browse this author →KAKEN DB | | Fujita, Misato Browse this author | | Tamura, Masato Browse this author →KAKEN DB |
| Keywords: | Glycine | | Angiogenesis | | PI3K | | Akt | | mTOR | | Zebrafish |
| Issue Date: | 27-Aug-2020 |
| Publisher: | Elsevier |
| Journal Title: | Biochemical and biophysical research communications |
| Volume: | 529 |
| Issue: | 3 |
| Start Page: | 596 |
| End Page: | 602 |
| Publisher DOI: | 10.1016/j.bbrc.2020.06.085 |
| PMID: | 32736679 |
| Abstract: | Glycine, a non-essential amino acid, exerts concentration-dependent biphasic effects on angiogenesis. Low-doses of glycine promote angiogenesis, whereas high-doses cause anti-angiogenesis. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling participates in angiogenesis of both physiological development, and pathological events including tumor and inflammation. We assessed the role of PI3K/Akt/mTOR signaling in vascular development, and the interaction with glycine, using transgenic zebrafish Tg(fli1a:Myr-mCherty)(ncv1) embryos expressing fluorescent proteins in vascular endothelial cells. Treatment with inhibitors of mTORC1 (rapamycin and everolimus), mTORC1/mTORC2 (KU0063794), PI3K (LY29400), and Akt (Akt inhibitor) decreased the development of intersegmental vessels (ISVs). These inhibitors cancelled the angiogenic effects of a low-dose of glycine, while acted synergistically with a high-dose of glycine in anti-angiogenesis. mTOR signaling regulates the gene expression of vascular endothelial growth factor (VEGF), a major angiogenic factor, and nitric oxide (NO) synthase (NOS), an enzyme for the synthesis of an angiogenic mediator NO. Expressions of VEGF and NOS were consistent with the vascular features induced by glycine and an mTOR inhibitor. Our results suggest that PI3K/Akt/mTOR signaling may interact with dose-dependent biphasic effects of exogenous glycine on in vivo angiogenesis. mTOR signaling is a key target for cancer therapy, thus, the combining mTOR inhibitors with glycine may be a potential approach for controlling angiogenesis. (C) 2020 Elsevier Inc. All rights reserved. |
| Rights: | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/82533 |
| Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 田村（辻） 潔美
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