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Original Article

Korean J Physiol Pharmacol 2020; 24(1): 69-79

Published online January 1, 2020 https://doi.org/10.4196/kjpp.2020.24.1.69

Copyright © The Korean Journal of Physiology & Pharmacology.

Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway

Seul Gi Kim1,3, Jin Young Sung1,3, Jae-Ryong Kim2,3, and Hyoung Chul Choi1,3,*

1Department of Pharmacology, 2Department of Biochemistry and Molecular Biology, 3Smart-aging Convergence Research Center, Yeungnam University College of Medicine, Daegu 42415, Korea

Correspondence to:*Hyoung Chul Choi
E-mail: hcchoi@med.yu.ac.kr

Received: August 16, 2019; Revised: October 22, 2019; Accepted: October 22, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H2O2) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the antiapoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

Keywords: Aging, AMP-activated protein kinase, Apoptosis, Quercetin, Vascular smooth muscle cell