Item type |
文献 / Documents(1) |
公開日 |
2022-09-20 |
アクセス権 |
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アクセス権 |
open access |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版社版DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1186/s13098-021-00755-z |
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言語 |
ja |
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関連名称 |
10.1186/s13098-021-00755-z |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
タイトル |
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タイトル |
Leucine imparts cardioprotective effects by enhancing mTOR activity and mitochondrial fusion in a myocardial ischemia/reperfusion injury murine model |
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言語 |
en |
著者 |
モリオ, アツシ
堤, 理恵
里見, 志帆
コンドウ, タカシ
ミヨシ, ヒロツグ
カトウ, タカヒロ
黒田, 雅士
キタムラ, タダヒロ
ハラ, ケンタ
サエキ, ノボル
阪上, 浩
堤, 保夫
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Background: Coronary artery disease is a leading cause of morbidity and mortality among patients with diabetes. Previously, we demonstrated that branched-chain amino acids (BCAAs) showed cardioprotective effects against cardiac ischemia/reperfusion (I/R) injury. A recent study suggested that leucine (Leu), a BCAA, is a key amino acid involved in mammalian target of rapamycin (mTOR) activity and mitochondrial function. However, whether Leu has cardioprotective effects on diabetic hearts is unclear. In this study, we examined the preconditioning effect of Leu treatment on high-fat diet (HFD)-induced obese mouse which simulate prediabetic heart. Methods: In vivo mice models of I/R injury were divided into the following groups: control, mTOR+/−, and high-fat diet (HFD)-induced obese groups. Mice were randomly administered with Leu, the mTOR inhibitor rapamycin (Rap), or Leu with Rap. Isolated rat cardiomyocytes were subjected to simulated I/R injury. Biochemical and mitochondrial functional assays were performed to evaluate the changes in mTOR activity and mitochondrial dynamics caused by Leu treatment. Results: Leu-treated mice showed a significant reduction in infarct size when compared with the control group (34.8% ± 3.8% vs. 43.1% ± 2.4%, n = 7, p < 0.05), whereas Rap-treated mice did not show the protective effects of Leu. This preconditioning effect of Leu was attenuated in mTOR+/− mice. Additionally, Leu increased the percentage of fused mitochondria and the mitochondrial volume, and decreased the number of mitochondria per cell in isolated cardiomyocytes. In HFD-induced obese mice, Leu treatment significantly reduced infarct size (41.0% ± 1.1% vs. 51.0% ± 1.4%, n = 7, p < 0.05), which was not induced by ischemic preconditioning, and this effect was inhibited by Rap. Furthermore, we observed enhanced mTOR protein expression and mitochondrial fusion with decreased reactive oxygen species production with Leu treatment in HFD-induced obese mice, but not in mTOR+/− mice. Conclusions: Leu treatment improved the damage caused by myocardial I/R injury by promoting mTOR activity and mitochondrial fusion on prediabetic hearts in mice. |
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言語 |
en |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Leucine |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
High-fat diet |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Myocardial ischemia/reperfusion injury |
キーワード |
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言語 |
en |
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主題Scheme |
Other |
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主題 |
Cardioprotective |
書誌情報 |
en : Diabetology & Metabolic Syndrome
巻 13,
p. 139,
発行日 2021-11-20
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収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
17585996 |
出版者 |
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出版者 |
BioMed Central |
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言語 |
en |
出版者 |
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出版者 |
Springer Nature |
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言語 |
en |
権利情報 |
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言語 |
en |
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権利情報 |
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
EID |
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識別子 |
389315 |
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識別子タイプ |
URI |
言語 |
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言語 |
eng |