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Pentamethylquercetin protects against cardiac remodeling via activation of Sestrin2.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Du JX,Wu JZ,Li Z,Zhang C,Shi MT,Zhao J,Jin MW,Liu H

doi

10.1016/j.bbrc.2019.03.031

subject

Has Abstract

pub_date

2019-04-30 00:00:00

pages

412-420

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30408-5

journal_volume

512

pub_type

杂志文章

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