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Biochem Biophys Res Commun. 2019 Apr 30;512(2):412-420. doi: 10.1016/j.bbrc.2019.03.031. Epub 2019 Mar 18.

Pentamethylquercetin protects against cardiac remodeling via activation of Sestrin2.

Author information

1
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Pharmacy, Medical College, Henan University of Science and Technology, Luoyang, China.
2
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
3
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, China.
4
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, China. Electronic address: liuh@hust.edu.cn.

Abstract

Oxidative stress is widely involved in pathophysiological processes of cardiac remodeling. Molecules associated with antioxidant functions may be ideal targets for reversing cardiac remodeling. Sestrin2 is the important component of endogenous antioxidant defense, while there is little information on the pathophysiological roles of it in cardiac remodeling. The aim of this study was to investigate whether Sestrin2 is closely involved in cardiac remodeling, and whether the protective effect of pentamethylquercetin (PMQ) on cardiac remodeling is related to upregulation of the Sestrin2 endogenous antioxidant system. We generated a transverse aorta constriction (TAC)-induced pressure-overload cardiac-remodeling model in mice, and also established an isoproterenol (ISO)-induced neonatal rat cardiomyocyte (NRCM) hypertrophy model. The data showed Sestrin2 expression was downregulated significantly, and Nrf2 and HO-1 expression was also reduced in myocardial tissue or NRCM of model group, whereas keap1 expression was upregulated. PMQ significantly ameliorated cardiac remodeling and rectified the abnormal expression of Sestrin2/Nrf2/keap1. Sestrin2 small interfering RNA (SiRNA) reduced the protective effect of PMQ on NRCMs, as well as abolished its regulating effect on the Nrf2/keap1 pathway. In conclusion, Sestrin2 may be an important target in the anti-myocardial remodeling of PMQ.

KEYWORDS:

Cardiac remodeling; Nrf2; Pentamethylquercetin; Sestrin 2; keap1

PMID:
30898320
DOI:
10.1016/j.bbrc.2019.03.031

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