Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway
10.4196/kjpp.2020.24.1.69
- Author:
Seul Gi KIM
1
;
Jin Young SUNG
;
Jae Ryong KIM
;
Hyoung Chul CHOI
Author Information
1. Department of Pharmacology, Yeungnam University College of Medicine, Daegu 42415, Korea. hcchoi@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Aging;
AMP-activated protein kinase;
Apoptosis;
Quercetin;
Vascular smooth muscle cell
- MeSH:
Aging;
AMP-Activated Protein Kinases;
Apoptosis;
Cardiovascular Diseases;
Cell Aging;
Hydrogen Peroxide;
Muscle, Smooth, Vascular;
Polyphenols;
Quercetin;
Risk Factors;
RNA, Small Interfering
- From:The Korean Journal of Physiology and Pharmacology
2020;24(1):69-79
- CountryRepublic of Korea
- Language:English
-
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 anti-apoptotic 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.
