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Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells
OBJECTIVES: We recently found low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished). We investigated whether atheroprotective unidirectional pulsatile shear stress affects the expression of PDCD4 in endothelial cells. METHODS...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953479/ https://www.ncbi.nlm.nih.gov/pubmed/24626527 http://dx.doi.org/10.1371/journal.pone.0091564 |
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author | Ge, Cheng Song, Jiantao Chen, Liang Wang, Lin Chen, Yifei Liu, Xinxin Zhang, Yu Zhang, Lining Zhang, Mei |
author_facet | Ge, Cheng Song, Jiantao Chen, Liang Wang, Lin Chen, Yifei Liu, Xinxin Zhang, Yu Zhang, Lining Zhang, Mei |
author_sort | Ge, Cheng |
collection | PubMed |
description | OBJECTIVES: We recently found low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished). We investigated whether atheroprotective unidirectional pulsatile shear stress affects the expression of PDCD4 in endothelial cells. METHODS AND RESULTS: En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. Immunoprecipitation revealed that pulsatile shear stress induced the coupling of ubiquitin with PDCD4 expression. The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome–mediated degradation of PDCD4. Gain of function and loss of function experiments showed that PDCD4 induced turnover (proliferation and apoptosis) of HUVECs. Low PDCD4 level was associated with reduced proliferation but not apoptosis or phosphorylation of endothelial nitric oxide synthase caused by pulsatile shear stress to help maintain the homeostasis of endothelial cells. CONCLUSIONS: Pulsatile shear stress induces ubiquitin-proteasome–mediated degradation of PDCD4 via a PI3K/Akt pathway in HUVECs. PDCD4 induces turnover (proliferation and apoptosis) of HUVECs. Low PDCD4 level is associated with reduced proliferation for maintenance of HUVEC homeostasis under pulsatile shear stress. |
format | Online Article Text |
id | pubmed-3953479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39534792014-03-18 Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells Ge, Cheng Song, Jiantao Chen, Liang Wang, Lin Chen, Yifei Liu, Xinxin Zhang, Yu Zhang, Lining Zhang, Mei PLoS One Research Article OBJECTIVES: We recently found low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished). We investigated whether atheroprotective unidirectional pulsatile shear stress affects the expression of PDCD4 in endothelial cells. METHODS AND RESULTS: En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. Application of unidirectional pulsatile shear stress to human umbilical vein endothelial cells (HUVECs) decreased PDCD4 protein but not mRNA level. Immunoprecipitation revealed that pulsatile shear stress induced the coupling of ubiquitin with PDCD4 expression. The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway was involved in this ubiquitin-proteasome–mediated degradation of PDCD4. Gain of function and loss of function experiments showed that PDCD4 induced turnover (proliferation and apoptosis) of HUVECs. Low PDCD4 level was associated with reduced proliferation but not apoptosis or phosphorylation of endothelial nitric oxide synthase caused by pulsatile shear stress to help maintain the homeostasis of endothelial cells. CONCLUSIONS: Pulsatile shear stress induces ubiquitin-proteasome–mediated degradation of PDCD4 via a PI3K/Akt pathway in HUVECs. PDCD4 induces turnover (proliferation and apoptosis) of HUVECs. Low PDCD4 level is associated with reduced proliferation for maintenance of HUVEC homeostasis under pulsatile shear stress. Public Library of Science 2014-03-13 /pmc/articles/PMC3953479/ /pubmed/24626527 http://dx.doi.org/10.1371/journal.pone.0091564 Text en © 2014 Ge et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ge, Cheng Song, Jiantao Chen, Liang Wang, Lin Chen, Yifei Liu, Xinxin Zhang, Yu Zhang, Lining Zhang, Mei Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title | Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title_full | Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title_fullStr | Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title_full_unstemmed | Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title_short | Atheroprotective Pulsatile Flow Induces Ubiquitin-Proteasome–Mediated Degradation of Programmed Cell Death 4 in Endothelial Cells |
title_sort | atheroprotective pulsatile flow induces ubiquitin-proteasome–mediated degradation of programmed cell death 4 in endothelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953479/ https://www.ncbi.nlm.nih.gov/pubmed/24626527 http://dx.doi.org/10.1371/journal.pone.0091564 |
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