Cargando…
Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy
The disruption of mitochondrial dynamics is responsible for the development of diabetic cardiomyopathy (DCM). However, the mechanisms that regulate the balance of mitochondrial fission and fusion are not well-understood. Wild-type, Mst1 transgenic and Mst1 knockout mice were induced with experimenta...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859113/ https://www.ncbi.nlm.nih.gov/pubmed/33553168 http://dx.doi.org/10.3389/fcell.2020.628842 |
_version_ | 1783646664690499584 |
---|---|
author | Feng, Xinyu Wang, Shanjie Yang, Xingjun Lin, Jie Man, Wanrong Dong, Yuan Zhang, Yan Zhao, Zhijing Wang, Haichang Sun, Dongdong |
author_facet | Feng, Xinyu Wang, Shanjie Yang, Xingjun Lin, Jie Man, Wanrong Dong, Yuan Zhang, Yan Zhao, Zhijing Wang, Haichang Sun, Dongdong |
author_sort | Feng, Xinyu |
collection | PubMed |
description | The disruption of mitochondrial dynamics is responsible for the development of diabetic cardiomyopathy (DCM). However, the mechanisms that regulate the balance of mitochondrial fission and fusion are not well-understood. Wild-type, Mst1 transgenic and Mst1 knockout mice were induced with experimental diabetes by streptozotocin injection. In addition, primary neonatal cardiomyocytes were isolated and cultured to simulate diabetes to explore the mechanisms. Echocardiograms and hemodynamic measurements revealed that Mst1 knockout alleviated left ventricular remodeling and cardiac dysfunction in diabetic mice. Mst1 knockdown significantly decreased the number of TUNEL-positive cardiomyocytes subjected to high-glucose (HG) medium culture. Immunofluorescence study indicated that Mst1 overexpression enhanced, while Mst1 knockdown mitigated mitochondrial fission in DCM. Mst1 participated in the regulation of mitochondrial fission by upregulating the expression of Drp1, activating Drp1(S616) phosphorylation and Drp1(S637) dephosphorylation, as well as promoting Drp1 recruitment to the mitochondria. Furthermore, Drp1 knockdown abolished the effects of Mst1 on mitochondrial fission, mitochondrial membrane potential and mitochondrial dysfunction in cardiomyocytes subjected to HG treatment. These results indicated that Mst1 knockout inhibits mitochondrial fission and alleviates left ventricular remodeling thus prevents the development of DCM. |
format | Online Article Text |
id | pubmed-7859113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78591132021-02-05 Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy Feng, Xinyu Wang, Shanjie Yang, Xingjun Lin, Jie Man, Wanrong Dong, Yuan Zhang, Yan Zhao, Zhijing Wang, Haichang Sun, Dongdong Front Cell Dev Biol Cell and Developmental Biology The disruption of mitochondrial dynamics is responsible for the development of diabetic cardiomyopathy (DCM). However, the mechanisms that regulate the balance of mitochondrial fission and fusion are not well-understood. Wild-type, Mst1 transgenic and Mst1 knockout mice were induced with experimental diabetes by streptozotocin injection. In addition, primary neonatal cardiomyocytes were isolated and cultured to simulate diabetes to explore the mechanisms. Echocardiograms and hemodynamic measurements revealed that Mst1 knockout alleviated left ventricular remodeling and cardiac dysfunction in diabetic mice. Mst1 knockdown significantly decreased the number of TUNEL-positive cardiomyocytes subjected to high-glucose (HG) medium culture. Immunofluorescence study indicated that Mst1 overexpression enhanced, while Mst1 knockdown mitigated mitochondrial fission in DCM. Mst1 participated in the regulation of mitochondrial fission by upregulating the expression of Drp1, activating Drp1(S616) phosphorylation and Drp1(S637) dephosphorylation, as well as promoting Drp1 recruitment to the mitochondria. Furthermore, Drp1 knockdown abolished the effects of Mst1 on mitochondrial fission, mitochondrial membrane potential and mitochondrial dysfunction in cardiomyocytes subjected to HG treatment. These results indicated that Mst1 knockout inhibits mitochondrial fission and alleviates left ventricular remodeling thus prevents the development of DCM. Frontiers Media S.A. 2021-01-21 /pmc/articles/PMC7859113/ /pubmed/33553168 http://dx.doi.org/10.3389/fcell.2020.628842 Text en Copyright © 2021 Feng, Wang, Yang, Lin, Man, Dong, Zhang, Zhao, Wang and Sun. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Feng, Xinyu Wang, Shanjie Yang, Xingjun Lin, Jie Man, Wanrong Dong, Yuan Zhang, Yan Zhao, Zhijing Wang, Haichang Sun, Dongdong Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title | Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title_full | Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title_fullStr | Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title_full_unstemmed | Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title_short | Mst1 Knockout Alleviates Mitochondrial Fission and Mitigates Left Ventricular Remodeling in the Development of Diabetic Cardiomyopathy |
title_sort | mst1 knockout alleviates mitochondrial fission and mitigates left ventricular remodeling in the development of diabetic cardiomyopathy |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859113/ https://www.ncbi.nlm.nih.gov/pubmed/33553168 http://dx.doi.org/10.3389/fcell.2020.628842 |
work_keys_str_mv | AT fengxinyu mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT wangshanjie mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT yangxingjun mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT linjie mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT manwanrong mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT dongyuan mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT zhangyan mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT zhaozhijing mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT wanghaichang mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy AT sundongdong mst1knockoutalleviatesmitochondrialfissionandmitigatesleftventricularremodelinginthedevelopmentofdiabeticcardiomyopathy |