Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation

The blood-brain barrier (BBB) is essential for the exchange of nutrient and ions to maintain the homeostasis of central nervous system (CNS). BBB dysfunction is commonly associated with the disruption of endothelial tight junctions and excess permeability, which results in various CNS diseases. Ther...

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Main Authors: Zhenguo Yang, Chunnian Huang, Yongfu Wu, Bing Chen, Wenqing Zhang, Jingjing Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-01-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2019.00002/full
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spelling doaj-573b01ece61943ac8a56636f61cc5a3c2020-11-24T22:03:16ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2019-01-011010.3389/fphys.2019.00002435523Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term StarvationZhenguo Yang0Zhenguo Yang1Chunnian Huang2Yongfu Wu3Bing Chen4Wenqing Zhang5Jingjing Zhang6Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaAffiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaThe blood-brain barrier (BBB) is essential for the exchange of nutrient and ions to maintain the homeostasis of central nervous system (CNS). BBB dysfunction is commonly associated with the disruption of endothelial tight junctions and excess permeability, which results in various CNS diseases. Therefore, maintaining the structural integrity and proper function of the BBB is essential for the homeostasis and physiological function of the CNS. Here, we showed that serum starvation disrupted the function of endothelial barrier as evidenced by decreased trans-endothelial electrical resistance, increased permeability, and redistribution of tight junction proteins such as Claudin-5 (Cldn5). Further analyses revealed that autophagy was activated and protected the integrity of endothelial barrier by scavenging ROS and inhibiting the redistribution of Cldn5 under starvation, as evidenced by accumulation of autophagic vacuoles and increased expression of LC3II/I, ATG5 and LAMP1. In addition, autophagosome was observed to package and eliminate the aggregated Cldn5 in cytosol as detected by immunoelectron microscopy (IEM) and stimulated emission depletion (STED) microscope. Moreover, Akt-mTOR-p70S6K pathway was found to be involved in the protective autophagy induced by starvation. Our data demonstrated that autophagy played an essential role in maintaining the integrity of endothelial barrier by regulating the localization of Cldn5 under starvation.https://www.frontiersin.org/article/10.3389/fphys.2019.00002/fullblood-brain barrierclaudin-5permeabilitystarvationautophagy
collection DOAJ
language English
format Article
sources DOAJ
author Zhenguo Yang
Zhenguo Yang
Chunnian Huang
Yongfu Wu
Bing Chen
Wenqing Zhang
Jingjing Zhang
spellingShingle Zhenguo Yang
Zhenguo Yang
Chunnian Huang
Yongfu Wu
Bing Chen
Wenqing Zhang
Jingjing Zhang
Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
Frontiers in Physiology
blood-brain barrier
claudin-5
permeability
starvation
autophagy
author_facet Zhenguo Yang
Zhenguo Yang
Chunnian Huang
Yongfu Wu
Bing Chen
Wenqing Zhang
Jingjing Zhang
author_sort Zhenguo Yang
title Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
title_short Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
title_full Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
title_fullStr Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
title_full_unstemmed Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
title_sort autophagy protects the blood-brain barrier through regulating the dynamic of claudin-5 in short-term starvation
publisher Frontiers Media S.A.
series Frontiers in Physiology
issn 1664-042X
publishDate 2019-01-01
description The blood-brain barrier (BBB) is essential for the exchange of nutrient and ions to maintain the homeostasis of central nervous system (CNS). BBB dysfunction is commonly associated with the disruption of endothelial tight junctions and excess permeability, which results in various CNS diseases. Therefore, maintaining the structural integrity and proper function of the BBB is essential for the homeostasis and physiological function of the CNS. Here, we showed that serum starvation disrupted the function of endothelial barrier as evidenced by decreased trans-endothelial electrical resistance, increased permeability, and redistribution of tight junction proteins such as Claudin-5 (Cldn5). Further analyses revealed that autophagy was activated and protected the integrity of endothelial barrier by scavenging ROS and inhibiting the redistribution of Cldn5 under starvation, as evidenced by accumulation of autophagic vacuoles and increased expression of LC3II/I, ATG5 and LAMP1. In addition, autophagosome was observed to package and eliminate the aggregated Cldn5 in cytosol as detected by immunoelectron microscopy (IEM) and stimulated emission depletion (STED) microscope. Moreover, Akt-mTOR-p70S6K pathway was found to be involved in the protective autophagy induced by starvation. Our data demonstrated that autophagy played an essential role in maintaining the integrity of endothelial barrier by regulating the localization of Cldn5 under starvation.
topic blood-brain barrier
claudin-5
permeability
starvation
autophagy
url https://www.frontiersin.org/article/10.3389/fphys.2019.00002/full
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