Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury

Life Sciences 245 巻 117368- 頁 2020-03-15 発行
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タイトル ( eng )
Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury
作成者
Satomi Shiho
Morio Atsushi
Miyoshi Hirotsugu
Tsutsumi Rie
Sakaue Hiroshi
収録物名
Life Sciences
245
開始ページ 117368
抄録
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.
著者キーワード
Amino acid
Ischemia
Reperfusion
mTOR
Mitochondria
内容記述
This work was supported by JSPS KAKENHI, Japan [grant number 19K09353].
言語
英語
資源タイプ 学術雑誌論文
出版者
Elsevier
発行日 2020-03-15
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。
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0024-3205
[DOI] 10.1016/j.lfs.2020.117368
[PMID] 32001270
[DOI] https://doi.org/10.1016/j.lfs.2020.117368
備考 Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months.