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C1q/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy

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Abstract
Autophagy is an important process in the pathogenesis of atherosclerosis. C1q/tumor necrosis factor-related protein 9 (CTRP9) is the closest adiponectin paralog. CTRP9 has anti-aging and anti-atherogenic effects, but its roles in autophagy and endothelial senescence are currently unknown. This study aimed to evaluate whether CTRP9 prevents palmitic acid (PA)-induced endothelial senescence by promoting autophagy. After no treatment or pre-treatment of human umbilical vein endothelial cells with CTRP9 prior to PA treatment, the level of senescence was measured by senescence associated acidic beta-galactosidase staining and the level of hyperphosphorylated pRB protein. Autophagy was evaluated by LC3 conversion and the level of p62/SQSTM1, a protein degraded during autophagy. Autophagosome-lysosome fusion was detected by fluorescence microscopy. Pre-treatment with CTRP9 attenuated PA-induced endothelial senescence. CTRP9 increased the conversion of LC3-I to LC3-II and decreased p62 levels in a time- and dose-dependent manner. Although both CTRP9 and PA treatment increased LC3 conversion, treatment with PA increased the expression level of p62 and decreased the fusion of autophagosomes and lysosomes, which represented decreased autophagic flux. However, pre-treatment with CTRP9 recovered the autophagic flux inhibited by PA. AMP-activated kinase (AMPK) activation was involved in LC3 conversion and decreased p62 levels induced by CTRP9. CTRP9 inhibits PA-induced endothelial senescence by recovering autophagy and autophagic flux through AMPK activation.
Author(s)
김휘승박중열유지희이우제이유라이지우정창희조윤경
Issued Date
2021
Type
Article
Keyword
C1q/TNF-Related protein-9Endothelial senescenceAutophagyAgingAtherosclerosis
DOI
10.1016/j.mce.2020.111114
URI
https://oak.ulsan.ac.kr/handle/2021.oak/6974
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2470025640&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,C1q%2FTNF-related%20protein-9%20attenuates%20palmitic%20acid-induced%20endothelial%20cell%20senescence%20via%20increasing%20autophagy&offset=0&pcAvailability=true
Publisher
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Location
아일랜드
Language
영어
ISSN
0303-7207
Citation Volume
521
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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