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C1q/TNF-related protein-9이 자가포식 증가를 통해 혈관내피세포 노화에 미치는 영향

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Abstract
Background: 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 purported anti-aging and anti-atherogenic effects, but its roles in autophagy and endothelial senescence are unknown. The aim of this study was to evaluate whether CTRP9 prevents palmitic acid (PA)-induced endothelial senescence by promoting autophagy.
Methods: 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 β-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.
Results: Pre-treatment with CTRP9 attenuated PA-induced endothelial senescence. CTRP9 increased the conversion of LC3-I to LC3-II, and decreased the level of p62 in time- and dose-dependent manners. Although both CTRP9 and PA treatment increased the LC3 conversion, treatment of PA increased 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 induced by CTRP9.
Conclusion: CTRP9 inhibits PA-induced endothelial senescence by recovering autophagy and autophagic flux through AMPK activation.
Author(s)
이지우
Issued Date
2020
Awarded Date
2021-02
Type
Dissertation
Keyword
C1q/TNF-related protein-9endothelial senescenceautophagyagingatherosclerosis
URI
https://oak.ulsan.ac.kr/handle/2021.oak/5798
http://ulsan.dcollection.net/common/orgView/200000363622
Alternative Author(s)
Jiwoo Lee
Affiliation
울산대학교
Department
일반대학원 의학과
Advisor
박중열
Degree
Doctor
Publisher
울산대학교 일반대학원 의학과
Language
eng
Rights
울산대학교 논문은 저작권에 의해 보호받습니다.
Appears in Collections:
Medicine > 2. Theses (Ph.D)
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