Research Paper Volume 12, Issue 5 pp 4178—4192
SIRT3 inhibits cardiac hypertrophy by regulating PARP-1 activity
- 1 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, PR. China
- 2 Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, PR. China
- 3 Aab Cardiovascular Research Institute, University of Rochester, West Henrietta, NY 14586, USA
- 4 Anhui Provincial Cardiovascular Institute, Hefei, Anhui, PR. China
- 5 Department of Pharmacology, School of Medicine, Shaoxing University, Shaoxing, PR. China
- 6 Equal contribution
received: June 4, 2019 ; accepted: January 24, 2020 ; published: March 4, 2020 ;https://doi.org/10.18632/aging.102862
How to Cite
Copyright © 2020 Feng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sirtuin 3 (SIRT3) is a type III histone deacetylase that inhibits cardiac hypertrophy. It is mainly localized in the mitochondria and is thus implicated in mitochondrial metabolism. Recent studies have shown that SIRT3 can also accumulate in the nuclear under stressed conditions, and participated in histone deacetylation of target proteins. Poly [ADP-ribose] polymerase 1 (PARP-1) functions as an important PARP isoform that was involved in cardiac hypertrophy. Our experiments showed that SIRT3 accumulated in the nuclear of cardiomyocytes treated with isoproterenol or SIRT3 overexpression. Moreover, overexpression of SIRT3 by adenovirus inhibited the expression of cardiac hypertrophic genes-ANF and BNP, as well as abrogating PARP-1 activation induced by isoproterenol or phenylephrine. In addition, co-immunoprecipitation experiments revealed that SIRT3 could interact with PARP-1, and overexpression of SIRT3 could decrease the acetylation level of PARP-1. Our results indicate that SIRT3 exerts protective effects against cardiac hypertrophy by reducing the level of acetylation and activity of PARP-1, thus providing novel mechanistic insights into SIRT3-mediated cardiprotective actions.