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Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway.
Mar Drugs. 2017 Apr 06; 15(4)MD

Abstract

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.

Authors+Show Affiliations

Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. Jingwang@qdio.ac.cn. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. Jingwang@qdio.ac.cn.School of Life Sciences, Nantong University, Seyuan Road 9, Nantong 226019, China. hold126@126.com.Taian City Central Hospital, Taian 271000, China. xuezhang@163.com.Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. xinpengli@163.com. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. xinpengli@163.com.Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. lihuageng@163.com. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. lihuageng@163.com.Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. iocwang@ucdavis.edu. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. iocwang@ucdavis.edu.Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China. qbzhang@qdio.ac.cn. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China. qbzhang@qdio.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28383489

Citation

Wang, Jing, et al. "Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells From H₂O₂-Induced Apoptosis By Affecting the PI3K/Akt Signaling Pathway." Marine Drugs, vol. 15, no. 4, 2017.
Wang J, Liu H, Zhang X, et al. Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway. Mar Drugs. 2017;15(4).
Wang, J., Liu, H., Zhang, X., Li, X., Geng, L., Zhang, H., & Zhang, Q. (2017). Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway. Marine Drugs, 15(4). https://doi.org/10.3390/md15040110
Wang J, et al. Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells From H₂O₂-Induced Apoptosis By Affecting the PI3K/Akt Signaling Pathway. Mar Drugs. 2017 Apr 6;15(4) PubMed PMID: 28383489.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfated Hetero-Polysaccharides Protect SH-SY5Y Cells from H₂O₂-Induced Apoptosis by Affecting the PI3K/Akt Signaling Pathway. AU - Wang,Jing, AU - Liu,Huaide, AU - Zhang,Xue, AU - Li,Xinpeng, AU - Geng,Lihua, AU - Zhang,Hong, AU - Zhang,Quanbin, Y1 - 2017/04/06/ PY - 2017/02/14/received PY - 2017/03/23/revised PY - 2017/04/04/accepted PY - 2017/4/7/entrez PY - 2017/4/7/pubmed PY - 2017/7/14/medline KW - PI3K/Akt KW - SH-SY5Y KW - oxidative stress KW - phosphorylate KW - sulfated hetero-polysaccharides JF - Marine drugs JO - Mar Drugs VL - 15 IS - 4 N2 - 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. SN - 1660-3397 UR - https://www.unboundmedicine.com/medline/citation/28383489/Sulfated_Hetero_Polysaccharides_Protect_SH_SY5Y_Cells_from_H₂O₂_Induced_Apoptosis_by_Affecting_the_PI3K/Akt_Signaling_Pathway_ L2 - https://www.mdpi.com/resolver?pii=md15040110 DB - PRIME DP - Unbound Medicine ER -