Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytopr...

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Main Authors: Jing Wang, Huaide Liu, Xuan Zhang, Xinpeng Li, Lihua Geng, Hong Zhang, Quanbin Zhang
Format: Article
Language:English
Published: MDPI AG 2017-04-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/15/4/110
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spelling doaj-5ebe0c4b148541aa900b304d6cd5d7e82020-11-24T22:58:08ZengMDPI AGMarine Drugs1660-33972017-04-0115411010.3390/md15040110md15040110Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling PathwayJing Wang0Huaide Liu1Xuan Zhang2Xinpeng Li3Lihua Geng4Hong Zhang5Quanbin Zhang6Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaSchool of Life Sciences, Nantong University, Seyuan Road 9, Nantong 226019, ChinaTaian City Central Hospital, Taian 271000, ChinaKey Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaKey Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaKey Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaKey Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, ChinaParkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.http://www.mdpi.com/1660-3397/15/4/110sulfated hetero-polysaccharidesPI3K/AktphosphorylateSH-SY5Yoxidative stress
collection DOAJ
language English
format Article
sources DOAJ
author Jing Wang
Huaide Liu
Xuan Zhang
Xinpeng Li
Lihua Geng
Hong Zhang
Quanbin Zhang
spellingShingle Jing Wang
Huaide Liu
Xuan Zhang
Xinpeng Li
Lihua Geng
Hong Zhang
Quanbin Zhang
Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
Marine Drugs
sulfated hetero-polysaccharides
PI3K/Akt
phosphorylate
SH-SY5Y
oxidative stress
author_facet Jing Wang
Huaide Liu
Xuan Zhang
Xinpeng Li
Lihua Geng
Hong Zhang
Quanbin Zhang
author_sort Jing Wang
title Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
title_short Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
title_full Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
title_fullStr Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
title_full_unstemmed Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H2O2-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway
title_sort sulfated hetero-polysaccharides protect sh-sy5y cells from h2o2-induced apoptosis by affecting the pi3k/akt signaling pathway
publisher MDPI AG
series Marine Drugs
issn 1660-3397
publishDate 2017-04-01
description Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.
topic sulfated hetero-polysaccharides
PI3K/Akt
phosphorylate
SH-SY5Y
oxidative stress
url http://www.mdpi.com/1660-3397/15/4/110
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