Korean J Physiol Pharmacol.  2020 Jan;24(1):69-79. 10.4196/kjpp.2020.24.1.69.

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

Affiliations
  • 1Department of Pharmacology, Yeungnam University College of Medicine, Daegu 42415, Korea. hcchoi@med.yu.ac.kr
  • 2Department of Biochemistry and Molecular Biology, Yeungnam University College of Medicine, Daegu 42415, Korea.
  • 3Smart-aging Convergence Research Center, Yeungnam University College of Medicine, Daegu 42415, Korea.

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.

Keyword

Aging; AMP-activated protein kinase; Apoptosis; Quercetin; Vascular smooth muscle cell

MeSH Terms

Aging
AMP-Activated Protein Kinases*
Apoptosis*
Cardiovascular Diseases
Cell Aging*
Hydrogen Peroxide
Muscle, Smooth, Vascular*
Polyphenols
Quercetin
Risk Factors
RNA, Small Interfering
AMP-Activated Protein Kinases
Hydrogen Peroxide
Polyphenols
Quercetin
RNA, Small Interfering
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