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Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway
Mitochondrial calcium uptake 1 (MICU1) is a pivotal molecule in maintaining mitochondrial homeostasis under stress conditions. However, it is unclear whether MICU1 attenuates mitochondrial stress in angiotensin II (Ang-II)-induced cardiac hypertrophy or if it has a role in the function of melatonin....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834983/ https://www.ncbi.nlm.nih.gov/pubmed/33259334 http://dx.doi.org/10.18632/aging.202159 |
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author | Yang, Yi Du, Jin Xu, Rui Shen, Yang Yang, Dachun Li, De Hu, Houxiang Pei, Haifeng Yang, Yongjian |
author_facet | Yang, Yi Du, Jin Xu, Rui Shen, Yang Yang, Dachun Li, De Hu, Houxiang Pei, Haifeng Yang, Yongjian |
author_sort | Yang, Yi |
collection | PubMed |
description | Mitochondrial calcium uptake 1 (MICU1) is a pivotal molecule in maintaining mitochondrial homeostasis under stress conditions. However, it is unclear whether MICU1 attenuates mitochondrial stress in angiotensin II (Ang-II)-induced cardiac hypertrophy or if it has a role in the function of melatonin. Here, small-interfering RNAs against MICU1 or adenovirus-based plasmids encoding MICU1 were delivered into left ventricles of mice or incubated with neonatal murine ventricular myocytes (NMVMs) for 48 h. MICU1 expression was depressed in hypertrophic myocardia and MICU1 knockdown aggravated Ang-II-induced cardiac hypertrophy in vivo and in vitro. In contrast, MICU1 upregulation decreased cardiomyocyte susceptibility to hypertrophic stress. Ang-II administration, particularly in NMVMs with MICU1 knockdown, led to significantly increased reactive oxygen species (ROS) overload, altered mitochondrial morphology, and suppressed mitochondrial function, all of which were reversed by MICU1 supplementation. Moreover, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α)/MICU1 expression in hypertrophic myocardia increased with melatonin. Melatonin ameliorated excessive ROS generation, promoted mitochondrial function, and attenuated cardiac hypertrophy in control but not MICU1 knockdown NMVMs or mice. Collectively, our results demonstrate that MICU1 attenuates Ang-II-induced cardiac hypertrophy by inhibiting mitochondria-derived oxidative stress. MICU1 activation may be the mechanism underlying melatonin-induced protection against myocardial hypertrophy. |
format | Online Article Text |
id | pubmed-7834983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-78349832021-02-03 Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway Yang, Yi Du, Jin Xu, Rui Shen, Yang Yang, Dachun Li, De Hu, Houxiang Pei, Haifeng Yang, Yongjian Aging (Albany NY) Research Paper Mitochondrial calcium uptake 1 (MICU1) is a pivotal molecule in maintaining mitochondrial homeostasis under stress conditions. However, it is unclear whether MICU1 attenuates mitochondrial stress in angiotensin II (Ang-II)-induced cardiac hypertrophy or if it has a role in the function of melatonin. Here, small-interfering RNAs against MICU1 or adenovirus-based plasmids encoding MICU1 were delivered into left ventricles of mice or incubated with neonatal murine ventricular myocytes (NMVMs) for 48 h. MICU1 expression was depressed in hypertrophic myocardia and MICU1 knockdown aggravated Ang-II-induced cardiac hypertrophy in vivo and in vitro. In contrast, MICU1 upregulation decreased cardiomyocyte susceptibility to hypertrophic stress. Ang-II administration, particularly in NMVMs with MICU1 knockdown, led to significantly increased reactive oxygen species (ROS) overload, altered mitochondrial morphology, and suppressed mitochondrial function, all of which were reversed by MICU1 supplementation. Moreover, peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α)/MICU1 expression in hypertrophic myocardia increased with melatonin. Melatonin ameliorated excessive ROS generation, promoted mitochondrial function, and attenuated cardiac hypertrophy in control but not MICU1 knockdown NMVMs or mice. Collectively, our results demonstrate that MICU1 attenuates Ang-II-induced cardiac hypertrophy by inhibiting mitochondria-derived oxidative stress. MICU1 activation may be the mechanism underlying melatonin-induced protection against myocardial hypertrophy. Impact Journals 2020-11-26 /pmc/articles/PMC7834983/ /pubmed/33259334 http://dx.doi.org/10.18632/aging.202159 Text en Copyright: © 2020 Yang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Yang, Yi Du, Jin Xu, Rui Shen, Yang Yang, Dachun Li, De Hu, Houxiang Pei, Haifeng Yang, Yongjian Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title | Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title_full | Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title_fullStr | Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title_full_unstemmed | Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title_short | Melatonin alleviates angiotensin-II-induced cardiac hypertrophy via activating MICU1 pathway |
title_sort | melatonin alleviates angiotensin-ii-induced cardiac hypertrophy via activating micu1 pathway |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834983/ https://www.ncbi.nlm.nih.gov/pubmed/33259334 http://dx.doi.org/10.18632/aging.202159 |
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