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ID 50462
本文ファイル
著者
Satomi, Shiho
Morio, Atsushi
Miyoshi, Hirotsugu
Tsutsumi, Rie
Sakaue, Hiroshi
Saeki, Noboru 大学院医系科学研究科(医) 広大研究者総覧
Tsutsumi, Yasuo M. 大学院医系科学研究科(医) 広大研究者総覧
キーワード
Amino acid
Ischemia
Reperfusion
mTOR
Mitochondria
抄録(英)
Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs.
Main methods: An in vivo model of I/R injury was tested in control, mTOR+/+, and mTOR+/−. Mice were randomly assigned to receive BCAAs, rapamycin, or BCAAs + rapamycin. Furthermore, isolated cardiomyocytes were subjected to simulated ischemia and cell death was quantified. Biochemical and mitochondrial swelling assays were also performed.
Key findings: Mice treated with BCAAs had a significant reduction in infarct size as a percentage of the area at risk compared to controls (34.1 ± 3.9% vs. 44.7 ± 2.6%, P = 0.001), whereas mice treated with the mTOR inhibitor rapamycin were not protected by BCAA administration (42.2 ± 6.5%, vs. control, P = 0.015). This protection was not detected in our hetero knockout mice of mTOR. Western blot analysis revealed no change in AKT signaling whereas activation of mTOR was identified. Furthermore, BCAAs prevented swelling which was reversed by the addition of rapamycin. In myocytes undergoing simulated I/R, BCAA treatment significantly preserved cell viability (71.7 ± 2.7% vs. 34.5 ± 1.6%, respectively, p < 0.0001), whereas rapamycin prevented this BCAA-induced cardioprotective effect (43.5 ± 3.4% vs. BCAA, p < 0.0001).
Significance: BCAA treatment exhibits a protective effect in myocardial I/R injury and that mTOR plays an important role in this preconditioning effect.
内容記述
This work was supported by JSPS KAKENHI, Japan [grant number 19K09353].
掲載誌名
Life Sciences
245巻
開始ページ
117368
出版年月日
2020-03-15
出版者
Elsevier
ISSN
0024-3205
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
© 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/
This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。
関連情報URL
部局名
医系科学研究科
病院
備考
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