Cargando…

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low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished).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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ge, Cheng, Song, Jiantao, Chen, Liang, Wang, Lin, Chen, Yifei, Liu, Xinxin, Zhang, Yu, Zhang, Lining, Zhang, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
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
_version_ 1782307362774712320
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low level of tumor suppressor programmed cell death 4 (PDCD4) associated with reduced atherosclerotic plaque area (unpublished).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
work_keys_str_mv AT gecheng atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT songjiantao atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT chenliang atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT wanglin atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT chenyifei atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT liuxinxin atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT zhangyu atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT zhanglining atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells
AT zhangmei atheroprotectivepulsatileflowinducesubiquitinproteasomemediateddegradationofprogrammedcelldeath4inendothelialcells