AARS2 ameliorates myocardial ischemia via fine-tuning PKM2-mediated metabolism
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| Publicado en: | bioRxiv (Jan 29, 2025) |
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| Autor principal: | |
| Otros Autores: | , , , , , , , |
| Publicado: |
Cold Spring Harbor Laboratory Press
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| Acceso en línea: | Citation/Abstract Full Text - PDF Full text outside of ProQuest |
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|---|---|---|---|
| 001 | 3161301079 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2692-8205 | ||
| 024 | 7 | |a 10.1101/2024.06.04.597368 |2 doi | |
| 035 | |a 3161301079 | ||
| 045 | 0 | |b d20250129 | |
| 100 | 1 | |a Zhang, Zongwang | |
| 245 | 1 | |a AARS2 ameliorates myocardial ischemia via fine-tuning PKM2-mediated metabolism | |
| 260 | |b Cold Spring Harbor Laboratory Press |c Jan 29, 2025 | ||
| 513 | |a Working Paper | ||
| 520 | 3 | |a AARS2, an alanyl-tRNA synthase, is essential for protein translation, but its function in mouse hearts is not fully addressed. Here, we found that cardiomyocyte-specific deletion of mouse AARS2 exhibited evident cardiomyopathy with impaired cardiac function, notable cardiac fibrosis and cardiomyocyte apoptosis. Cardiomyocyte-specific AARS2 overexpression in mice improved cardiac function and reduced cardiac fibrosis after myocardial infarction (MI), without affecting cardiomyocyte proliferation and coronary angiogenesis. Mechanistically, AARS2 overexpression suppressed cardiomyocyte apoptosis and mitochondrial reactive oxide species production, and changed cellular metabolism from oxidative phosphorylation toward glycolysis in cardiomyocytes, thus leading to cardiomyocyte survival from ischemia and hypoxia stress. Ribo-Seq revealed that AARS2 overexpression increased pyruvate kinase M2 (PKM2) protein translation and the ratio of PKM2 dimers to tetramers that promote glycolysis. Additionally, PKM2 activator TEPP-46 reversed cardiomyocyte apoptosis and cardiac fibrosis caused by AARS2 deficiency. Thus, this study demonstrates that AARS2 plays an essential role in protecting cardiomyocytes from ischemic pressure via fine-tuning PKM2-mediated energy metabolism, and presents a novel cardiac protective AARS2-PKM2 signaling during the pathogenesis of MI.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Introduction revised; Results revised; Discussion revised; Materials and methodscrevised; | |
| 653 | |a Pyruvic acid | ||
| 653 | |a tRNA | ||
| 653 | |a Heart | ||
| 653 | |a Energy metabolism | ||
| 653 | |a Phosphorylation | ||
| 653 | |a Hypoxia | ||
| 653 | |a Oxidative phosphorylation | ||
| 653 | |a Metabolism | ||
| 653 | |a Myocardial infarction | ||
| 653 | |a Apoptosis | ||
| 653 | |a Kinases | ||
| 653 | |a Cardiomyopathy | ||
| 653 | |a Pyruvate kinase | ||
| 653 | |a Cell survival | ||
| 653 | |a Translation | ||
| 653 | |a Myocardial ischemia | ||
| 653 | |a Cardiomyocytes | ||
| 653 | |a Angiogenesis | ||
| 653 | |a Glycolysis | ||
| 653 | |a Oxidative metabolism | ||
| 653 | |a Ischemia | ||
| 653 | |a Fibrosis | ||
| 653 | |a Cardiac function | ||
| 653 | |a Protein turnover | ||
| 700 | 1 | |a Zheng, Lixia | |
| 700 | 1 | |a Chen, Yang | |
| 700 | 1 | |a Chen, Yuanyuan | |
| 700 | 1 | |a Hou, Junjie | |
| 700 | 1 | |a Xiao, Chenglu | |
| 700 | 1 | |a Zhu, Xiaojun | |
| 700 | 1 | |a Zhao, Shimin | |
| 700 | 1 | |a Jing-Wei, Xiong | |
| 773 | 0 | |t bioRxiv |g (Jan 29, 2025) | |
| 786 | 0 | |d ProQuest |t Biological Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3161301079/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3161301079/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full text outside of ProQuest |u https://www.biorxiv.org/content/10.1101/2024.06.04.597368v2 |