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Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium

Authors
 Seung-Hyun Lee  ;  Jaesung Seo  ;  Soo-Yeon Park  ;  Mi-Hyeon Jeong  ;  Hyo-Kyoung Choi  ;  Chan Joo Lee  ;  Mi Jeong Kim  ;  Garam Guk  ;  SooYeon Lee  ;  Hyewon Park  ;  Jae-Wook Jeong  ;  Chang Hoon Ha  ;  Sungha Park  ;  Ho-Geun Yoon 
Citation
 Proceedings of the National Academy of Sciences of the United States of America, Vol.115(18) : 4672-4677, 2018 
Journal Title
 Proceedings of the National Academy of Sciences of the United States of America 
ISSN
 0027-8424 
Issue Date
2018
Keywords
AKT ; HDAC3 ; PDCD5 ; atherosclerosis ; endothelium
Abstract
Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5(L6R), an HDAC3-binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162313
Full Text
http://www.pnas.org/content/115/18/4672
DOI
10.1073/pnas.1712918115
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
김미정(Kim, Mi Jeong) ORCID logo https://orcid.org/0000-0002-0758-7145
박성하(Park, Sung Ha) ORCID logo https://orcid.org/0000-0001-5362-478X
박수연(Park, Soo Yeon) ORCID logo https://orcid.org/0000-0003-3743-9554
윤호근(Yoon, Ho Geun) ORCID logo https://orcid.org/0000-0003-2718-3372
이승현(Lee, Seung Hyun) ORCID logo https://orcid.org/0000-0001-7549-9430
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