Cargando…

Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats

This study aimed to estimate the role of phosphatidylethanolamine binding protein 1 (PEBP1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) model in adult male Sprague Dawley rats (250–280 g) were established and cult...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhong, Bu, Jiyuan, Yao, Xiyang, Liu, Chenglin, Shen, Haitao, Li, Xiang, Li, Haiying, Chen, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671526/
https://www.ncbi.nlm.nih.gov/pubmed/29163033
http://dx.doi.org/10.3389/fnmol.2017.00358
_version_ 1783276250860617728
author Wang, Zhong
Bu, Jiyuan
Yao, Xiyang
Liu, Chenglin
Shen, Haitao
Li, Xiang
Li, Haiying
Chen, Gang
author_facet Wang, Zhong
Bu, Jiyuan
Yao, Xiyang
Liu, Chenglin
Shen, Haitao
Li, Xiang
Li, Haiying
Chen, Gang
author_sort Wang, Zhong
collection PubMed
description This study aimed to estimate the role of phosphatidylethanolamine binding protein 1 (PEBP1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) model in adult male Sprague Dawley rats (250–280 g) were established and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Expression vectors encoding wild-type PEBP1 and PEBP1 with Ser153Ala mutation (S153A), PEBP1 specific siRNAs, and human recombinant PEBP1 (rhPEBP1) were administered intracerebroventricularly. Endogenous PEBP1 level and its phosphorylation at Ser153 were increased within penumbra tissue and cultured neurons after I/R, accompanied by decreased interaction between PEBP1 and Raf-1. There was a trend toward increased Raf-1/MEK/ERK/NF-κB signaling pathway and phosphatidylcholine-phospholipase C (PC-PLC) activity after I/R, which was enhanced by wild-type PEBP1overexpression and rhPEBP1 treatment and inhibited by PEBP1 (S153A) overexpression. And PEBP1 (S153A) overexpression increased its interaction with Raf-1, reduced infarct size, neuronal death and inflammation, and improved neurological function after I/R, while wild-type PEBP1overexpression exerted opposite effects, suggesting that phosphorylation at Ser153 may exert as a functional switch of PEBP1 by switching PEBP1 from Raf-1 inhibition to PC-PLC activation following I/R. Compared with PEBP1 knockdown, PEBP1 (S153A) overexpression exerted a better rescue effect on I/R injury, which further proved that PEBP1 may be a good protein gone bad with phosphorylation at S153 as a functional switch following I/R. Collectively, our findings suggest that PEBP1 contributed to neuronal death and inflammation after I/R. Selective inhibition of PEBP1 phosphorylation may be a novel approach to ameliorate I/R injury.
format Online
Article
Text
id pubmed-5671526
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-56715262017-11-21 Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats Wang, Zhong Bu, Jiyuan Yao, Xiyang Liu, Chenglin Shen, Haitao Li, Xiang Li, Haiying Chen, Gang Front Mol Neurosci Neuroscience This study aimed to estimate the role of phosphatidylethanolamine binding protein 1 (PEBP1) in cerebral ischemia-reperfusion (I/R) injury and the underlying mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) model in adult male Sprague Dawley rats (250–280 g) were established and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic I/R injury in vitro. Expression vectors encoding wild-type PEBP1 and PEBP1 with Ser153Ala mutation (S153A), PEBP1 specific siRNAs, and human recombinant PEBP1 (rhPEBP1) were administered intracerebroventricularly. Endogenous PEBP1 level and its phosphorylation at Ser153 were increased within penumbra tissue and cultured neurons after I/R, accompanied by decreased interaction between PEBP1 and Raf-1. There was a trend toward increased Raf-1/MEK/ERK/NF-κB signaling pathway and phosphatidylcholine-phospholipase C (PC-PLC) activity after I/R, which was enhanced by wild-type PEBP1overexpression and rhPEBP1 treatment and inhibited by PEBP1 (S153A) overexpression. And PEBP1 (S153A) overexpression increased its interaction with Raf-1, reduced infarct size, neuronal death and inflammation, and improved neurological function after I/R, while wild-type PEBP1overexpression exerted opposite effects, suggesting that phosphorylation at Ser153 may exert as a functional switch of PEBP1 by switching PEBP1 from Raf-1 inhibition to PC-PLC activation following I/R. Compared with PEBP1 knockdown, PEBP1 (S153A) overexpression exerted a better rescue effect on I/R injury, which further proved that PEBP1 may be a good protein gone bad with phosphorylation at S153 as a functional switch following I/R. Collectively, our findings suggest that PEBP1 contributed to neuronal death and inflammation after I/R. Selective inhibition of PEBP1 phosphorylation may be a novel approach to ameliorate I/R injury. Frontiers Media S.A. 2017-10-31 /pmc/articles/PMC5671526/ /pubmed/29163033 http://dx.doi.org/10.3389/fnmol.2017.00358 Text en Copyright © 2017 Wang, Bu, Yao, Liu, Shen, Li, Li and Chen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Wang, Zhong
Bu, Jiyuan
Yao, Xiyang
Liu, Chenglin
Shen, Haitao
Li, Xiang
Li, Haiying
Chen, Gang
Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title_full Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title_fullStr Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title_full_unstemmed Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title_short Phosphorylation at S153 as a Functional Switch of Phosphatidylethanolamine Binding Protein 1 in Cerebral Ischemia-Reperfusion Injury in Rats
title_sort phosphorylation at s153 as a functional switch of phosphatidylethanolamine binding protein 1 in cerebral ischemia-reperfusion injury in rats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671526/
https://www.ncbi.nlm.nih.gov/pubmed/29163033
http://dx.doi.org/10.3389/fnmol.2017.00358
work_keys_str_mv AT wangzhong phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT bujiyuan phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT yaoxiyang phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT liuchenglin phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT shenhaitao phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT lixiang phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT lihaiying phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats
AT chengang phosphorylationats153asafunctionalswitchofphosphatidylethanolaminebindingprotein1incerebralischemiareperfusioninjuryinrats