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

Type
Academic journal
Author
Journal
The Korean Society Of Pharmacology The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제24권 제1호 KCI Accredited Journals
Published
2020.1
Pages
69 - 79 (11page)

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

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References (37)

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Lakatta EG / 2003 / Arterial and cardiac aging : major shareholders in cardiovascular disease enterprises : part I : aging arteries : a"set up"for vascular disease / Circulation 107:139~146 google schola von Zglinicki T / 2003 / Telomere-driven replicative senescence is a stress response / Nat Biotechnol 21:229~230 google schola Toussaint O / 2000 / Cellular and molecular mechanisms of stress-induced premature senescence(SIPS)of human diploid fibroblasts and melanocytes / Exp Gerontol 35:927~945 google schola Dimri GP / 1995 / A biomarker that identifies senescent human cells in culture and in aging skin in vivo / Proc Natl Acad Sci U S A 92:9363~9367 google schola Salminen A / 2011 / Apoptosis and aging : increased resistance to apoptosis enhances the aging process / Cell Mol Life Sci 68:1021~1031 google schola

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