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RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy
http://hdl.handle.net/10422/00013554
http://hdl.handle.net/10422/000135543e5a9c10-4916-488b-9a20-35d6a75cc8fc
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
j.jbc.2023.102993 (7.0 MB)
|
This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/). |
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2023-05-09 | |||||
| タイトル | ||||||
| タイトル | RhoA rescues cardiac senescence by regulating Parkin-mediated mitophagy | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | cardiomyocyte | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | cardiomyopathy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | mitophagy | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Parkin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Ras homolog gene family | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | member A (RhoA) | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | senescence | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | signal transduction | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
SOH, Joanne Ern Chi
× SOH, Joanne Ern Chi× SHIMIZU, Akio× MOLLA, Md Rasel× ZANKOV, Dimitar Petrov× NGUYEN, Le Kim Chi× RAHMAN KHAN, Mahbubur× TESEGA, Wondwossen Wale× CHEN, Si× TOJO, Misa× ITOH, Yoshito× SATO, Akira× HITOSUGI, Masahito× MIYAGAWA, Shigeru× OGITA, Hisakazu |
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| 著者別名 |
清水, 昭男
× 清水, 昭男× 東條, 美紗× 佐藤, 朗× 一杉, 正仁× 扇田, 久和 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Heart failure is one of the leading causes of death worldwide. RhoA, a small GTPase, governs actin dynamics in various tissue and cell types, including cardiomyocytes; however, its involvement in cardiac function has not been fully elucidated. Here, we generated cardiomyocyte-specific RhoA conditional knockout (cKO) mice, which demonstrated a significantly shorter lifespan with left ventricular dilation and severely impaired ejection fraction. We found that the cardiac tissues of the cKO mice exhibited structural disorganization with fibrosis and also exhibited enhanced senescence compared with control mice. In addition, we show that cardiomyocyte mitochondria were structurally abnormal in the aged cKO hearts. Clearance of damaged mitochondria by mitophagy was remarkably inhibited in both cKO cardiomyocytes and RhoA-knockdown HL-1 cultured cardiomyocytes. In RhoA-depleted cardiomyocytes, we reveal that the expression of Parkin, an E3 ubiquitin ligase that plays a crucial role in mitophagy, was reduced, and expression of N-Myc, a negative regulator of Parkin, was increased. We further reveal that the RhoA-Rho kinase axis induced N-Myc phosphorylation, which led to N-Myc degradation and Parkin upregulation. Re-expression of Parkin in RhoA-depleted cardiomyocytes restored mitophagy, reduced mitochondrial damage, attenuated cardiomyocyte senescence, and rescued cardiac function both in vitro and in vivo. Finally, we found that patients with idiopathic dilated cardiomyopathy without causal mutations for dilated cardiomyopathy showed reduced cardiac expression of RhoA and Parkin. These results suggest that RhoA promotes Parkin-mediated mitophagy as an indispensable mechanism contributing to cardioprotection in the aging heart. | |||||
| 書誌情報 |
en : Journal of Biological Chemistry 巻 299, 号 3, 発行日 2023-03 |
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| 出版者 | ||||||
| 出版者 | American Society for Biochemistry and Molecular Biology Inc. | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0021-9258 | |||||
| PMID | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 36758801 | |||||
| PMCID | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10020657/ | |||||
| 関連名称 | PMC10020657 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.jbc.2023.102993 | |||||
| 関連名称 | 10.1016/j.jbc.2023.102993 | |||||
| 権利 | ||||||
| 権利情報 | © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Journal Article | |||||
