1. Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium
- Author
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Jaesung Seo, Chang Hoon Ha, Hyo Kyoung Choi, Jae Wook Jeong, Chan Joo Lee, Garam Guk, Ho-Geun Yoon, Mi Jeong Kim, Sungha Park, Seung-Hyun Lee, Soo-Yeon Park, Mi Hyeon Jeong, Hyewon Park, and Soo Yeon Lee
- Subjects
0301 basic medicine ,Programmed cell death ,Endothelium ,Apoptosis ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Enos ,medicine ,Endothelial dysfunction ,Protein kinase B ,Multidisciplinary ,biology ,Biological Sciences ,medicine.disease ,biology.organism_classification ,Cytoprotection ,Neoplasm Proteins ,Nitric oxide synthase ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Apoptosis Regulatory Proteins - 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 PDCD5L6R, 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.
- Published
- 2018