SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485

Aging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging‐related vascular diseases. Sirtuin‐1 (SIRT1) and AMP‐activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects h...

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Main Authors: Jin Young Sung, Seul Gi Kim, Du Hyong Cho, Jae‐Ryong Kim, Hyoung Chul Choi
Format: Article
Language:English
Published: Wiley 2020-07-01
Series:FEBS Open Bio
Subjects:
Online Access:https://doi.org/10.1002/2211-5463.12895
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author Jin Young Sung
Seul Gi Kim
Du Hyong Cho
Jae‐Ryong Kim
Hyoung Chul Choi
author_facet Jin Young Sung
Seul Gi Kim
Du Hyong Cho
Jae‐Ryong Kim
Hyoung Chul Choi
author_sort Jin Young Sung
collection DOAJ
description Aging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging‐related vascular diseases. Sirtuin‐1 (SIRT1) and AMP‐activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects have not been well characterized. To determine the nature of the interaction between SIRT1 and AMPK in VSMC senescence, we investigated the effects of SRT1720 on its downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485. During Adriamycin‐induced VSMC senescence, SRT1720 increased the activity of SIRT1 and AMPKα phosphorylation at Ser485 via the cAMP–protein kinase A (PKA) pathway. Telomere length and telomerase reverse transcriptase expression were increased by SIRT1 activation with SRT1720. Taken together, these data show that activation of the SIRT1/cAMP–PKA/p‐AMPKα (Ser485) pathway may be an effective antisenescence mechanism for VSMCs.
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spelling doaj.art-e884b1e35a0045f3808f314f1ffac48d2023-05-23T06:51:07ZengWileyFEBS Open Bio2211-54632020-07-011071316132510.1002/2211-5463.12895SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485Jin Young Sung0Seul Gi Kim1Du Hyong Cho2Jae‐Ryong Kim3Hyoung Chul Choi4Department of Pharmacology College of Medicine Yeungnam University Daegu KoreaDepartment of Pharmacology College of Medicine Yeungnam University Daegu KoreaDepartment of Pharmacology College of Medicine Yeungnam University Daegu KoreaSmart‐aging Convergence Research Center College of Medicine Yeungnam University Daegu KoreaDepartment of Pharmacology College of Medicine Yeungnam University Daegu KoreaAging is a major risk factor for hypertension and atherosclerosis, and vascular smooth muscle cell (VSMC) senescence can promote aging‐related vascular diseases. Sirtuin‐1 (SIRT1) and AMP‐activated protein kinase (AMPK) were previously reported to modulate vascular senescence; however, its effects have not been well characterized. To determine the nature of the interaction between SIRT1 and AMPK in VSMC senescence, we investigated the effects of SRT1720 on its downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485. During Adriamycin‐induced VSMC senescence, SRT1720 increased the activity of SIRT1 and AMPKα phosphorylation at Ser485 via the cAMP–protein kinase A (PKA) pathway. Telomere length and telomerase reverse transcriptase expression were increased by SIRT1 activation with SRT1720. Taken together, these data show that activation of the SIRT1/cAMP–PKA/p‐AMPKα (Ser485) pathway may be an effective antisenescence mechanism for VSMCs.https://doi.org/10.1002/2211-5463.12895p‐AMPK (Ser485)SIRT1SRT1720telomere lengthVSMC senescence
spellingShingle Jin Young Sung
Seul Gi Kim
Du Hyong Cho
Jae‐Ryong Kim
Hyoung Chul Choi
SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
FEBS Open Bio
p‐AMPK (Ser485)
SIRT1
SRT1720
telomere length
VSMC senescence
title SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
title_full SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
title_fullStr SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
title_full_unstemmed SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
title_short SRT1720‐induced activation of SIRT1 alleviates vascular smooth muscle cell senescence through PKA‐dependent phosphorylation of AMPKα at Ser485
title_sort srt1720 induced activation of sirt1 alleviates vascular smooth muscle cell senescence through pka dependent phosphorylation of ampkα at ser485
topic p‐AMPK (Ser485)
SIRT1
SRT1720
telomere length
VSMC senescence
url https://doi.org/10.1002/2211-5463.12895
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