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

Autor: Hyoung Chul Choi, Jae-Ryong Kim, Du Hyong Cho, Seul Gi Kim, Jin Young Sung
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Senescence
Vascular smooth muscle
p‐AMPK (Ser485)
AMP-Activated Protein Kinases
SRT1720
Heterocyclic Compounds
4 or More Rings
environment and public health
Muscle
Smooth
Vascular
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
SIRT1
Sirtuin 1
Serine
telomere length
Animals
Telomerase reverse transcriptase
Phosphorylation
Protein kinase A
lcsh:QH301-705.5
Cells
Cultured
Cellular Senescence
Research Articles
Chemistry
Kinase
AMPK
food and beverages
VSMC senescence
Cyclic AMP-Dependent Protein Kinases
Rats
Telomere
Cell biology
enzymes and coenzymes (carbohydrates)
030104 developmental biology
lcsh:Biology (General)
030220 oncology & carcinogenesis
hormones
hormone substitutes
and hormone antagonists
Research Article
Zdroj: FEBS Open Bio, Vol 10, Iss 7, Pp 1316-1325 (2020)
FEBS Open Bio
ISSN: 2211-5463
Popis: 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.
Sirtuin‐1 (SIRT1) and AMP‐activated protein kinase (AMPK) were reported to modulate vascular senescence. We investigated the effects of SRT1720 on downstream targets of SIRT1 and the phosphorylation of AMPKα at Ser485. During Adriamycin‐induced vascular smooth muscle cell senescence, SRT1720 increased the activity of SIRT1 and AMPKα phosphorylation at Ser485 via the cAMP–protein kinase A (PKA) pathway and telomerase reverse transcriptase expression. Activation of the SIRT1/cAMP–PKA/p‐AMPKα (Ser485) pathway may be an effective antisenescence mechanism for vascular smooth muscle cell.
Databáze: OpenAIRE
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