Rap1GAP Mediates Angiotensin II-Induced Cardiomyocyte Hypertrophy by Inhibiting Autophagy and Increasing Oxidative Stress.
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2021
2021
Historique:
received:
01
08
2020
revised:
05
03
2021
accepted:
18
03
2021
entrez:
3
5
2021
pubmed:
4
5
2021
medline:
20
5
2021
Statut:
epublish
Résumé
Abnormal autophagy and oxidative stress contribute to angiotensin II- (Ang II-) induced cardiac hypertrophy and heart failure. We previously showed that Ang II increased Rap1GAP gene expression in cardiomyocytes associated with hypertrophy and autophagy disorders. Using real-time PCR and Western blot, we found that Rap1GAP expression was increased in the heart of Sprague Dawley (SD) rats infused by Ang II compared with saline infusion and in Ang II vs. vehicle-treated rat neonatal cardiomyocytes. Overexpression of Rap1GAP in cultured cardiomyocytes exacerbated Ang II-induced cardiomyocyte hypertrophy, reactive oxygen species (ROS) generation, and cell apoptosis and inhibited autophagy. The increased oxidative stress caused by Rap1GAP overexpression was inhibited by the treatment of autophagy agonists. Knockdown of Rap1GAP by siRNA markedly attenuated Ang II-induced cardiomyocyte hypertrophy and oxidative stress and enhanced autophagy. The AMPK/AKT/mTOR signaling pathway was inhibited by overexpression of Rap1GAP and activated by the knockdown of Rap1GAP. These results show that Rap1GAP-mediated pathway might be a new mechanism of Ang II-induced cardiomyocyte hypertrophy, which could be a potential target for the future treatment of cardiac hypertrophy and heart failure.
Identifiants
pubmed: 33936386
doi: 10.1155/2021/7848027
pmc: PMC8062190
doi:
Substances chimiques
GTPase-Activating Proteins
0
Rap1GAP protein, mouse
0
Angiotensin II
11128-99-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7848027Informations de copyright
Copyright © 2021 Yan Gao et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflict of interest.
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