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Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium
- Publication Year :
- 2018
- Publisher :
- National Academy of Sciences, 2018.
-
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.
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....ca078994cf9322a013fc8562780092ac