Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3 Signaling Pathway

doi:10.3390/ijms18020315

科研成果详情

题名	Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3 Signaling Pathway
作者	Li, Zhengmao 1; Wu, Fenzan 2; Zhang, Xie 3; Chai, Yi 4; Chen, Daqing5; Yang, Yuetao5; Xu, Kebin 1; Yin, Jiayu 1; Li, Rui 1; Shi, Hongxue1; Wang, Zhouguang 1; Li, Xiaokun1,6; Xiao, Jian1; Zhang, Hongyu1
发表日期	2017-02
发表期刊	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	ER stress valproate apoptosis neurological disorders neurite outgrowth
其他关键词	UNFOLDED PROTEIN RESPONSE ; ACID-MEDIATED NEUROPROTECTION ; SPINAL-CORD-INJURY ; ER STRESS ; PARKINSONS-DISEASE ; GLIOBLASTOMA CELLS ; BIPOLAR DISORDER ; SODIUM VALPROATE ; ALPHA-SYNUCLEIN ; DOWN-REGULATION
摘要	Endoplasmic reticulum (ER) stress-induced apoptosis plays an important role in a range of neurological disorders, such as neurodegenerative diseases, spinal cord injury, and diabetic neuropathy. Valproate (VPA), a typical antiepileptic drug, is commonly used in the treatment of bipolar disorder and epilepsy. Recently, VPA has been reported to exert neurotrophic effects and promote neurite outgrowth, but its molecular mechanism is still unclear. In the present study, we investigated whether VPA inhibited ER stress and promoted neuroprotection and neuronal restoration in SH-SY5Y cells and in primary rat cortical neurons, respectively, upon exposure to thapsigargin (TG). In SH-SY5Y cells, cell viability was detected by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and the expression of ER stress-related apoptotic proteins such as glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), and cleaved caspase-12/-3 were analyzed with Western blot analyses and immunofluorescence assays. To explore the pathway involved in VPA-induced cell proliferation, we also examined p-AKT, GSK3, p-JNK and MMP-9. Moreover, to detect the effect of VPA in primary cortical neurons, immunofluorescence staining of -III tubulin and Anti-NeuN was analyzed in primary cultured neurons exposed to TG. Our results demonstrated that VPA administration improved cell viability in cells exposed to TG. In addition, VPA increased the levels of GRP78 and p-AKT and decreased the levels of ATF6, XBP-1, GSK3, p-JNK and MMP-9. Furthermore, the levels of the ER stress-induced apoptosis response proteins CHOP, cleaved caspase-12 and cleaved caspase-3 were inhibited by VPA treatment. Meanwhile, VPA administration also increased the ratio of Bcl-2/Bax. Moreover, VPA can maintain neurite outgrowth of primary cortical neurons. Collectively, the neurotrophic effect of VPA is related to the inhibition of ER stress-induced apoptosis in SH-SY5Y cells and the maintenance of neuronal growth. Collectively, our results suggested a new approach for the therapeutic function of VPA in neurological disorders and neuroprotection.
资助项目	Zhejiang Provincial Natural Science Funding [LY14H150010, LQ16H090007, LY14H170002]; National Natural Science Funding of ChinaNational Natural Science Foundation of China (NSFC) [81472165, 81372112, 81302775]; Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents; Zhejiang Provincial Program of Medical and Health Science [2014KYA131]; Ningbo Natural Science Funding [2015A610182, 2015A610208]
出版者	MDPI
出版地	BASEL
ISSN	1422-0067
EISSN	1422-0067
卷号	18 期号:2 页码:315
DOI	10.3390/ijms18020315
页数	16
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS记录号	WOS:000395457700084
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	28208696
PMC记录号	PMC5343851
SCOPUSEID	2-s2.0-85012113186
通讯作者地址	[Zhang, Hongyu]Key Laboratory of Biotechnology and Pharmaceutical Engineering,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Catalysis;Molecular Biology;Spectroscopy;Computer Science Applications;Physical and Theoretical Chemistry;Organic Chemistry;Inorganic Chemistry
引用统计	被引频次：29[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/9358
专题	药学院（分析测试中心）附属第二医院第二临床医学院、附属第二医院、育英儿童医院研究生工作部（研究生院）其他_附属慈溪医院（慈溪市人民医院）
通讯作者	Zhang, Hongyu
作者单位	1.Key Laboratory of Biotechnology and Pharmaceutical Engineering,School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou,325035,China; 2.Science and Education division,Cixi People’s Hospital,Wenzhou Medical University,Ningbo,315300,China; 3.Ningbo Medical Treatment Center,Li Huili Hospital,Ningbo,315000,China; 4.Department of neurosurgery,The second Affiliated Hospital,Nanchang University,Nanchang,330006,China; 5.Emergency Department,The Second Affiliated Hospital,Wenzhou Medical University,Wenzhou,325035,China; 6.Institute of Life Sciences,Wenzhou University,Wenzhou,325035,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Li, Zhengmao,Wu, Fenzan,Zhang, Xie,et al. Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3 Signaling Pathway[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2017,18(2):315.
APA	Li, Zhengmao., Wu, Fenzan., Zhang, Xie., Chai, Yi., Chen, Daqing., ... & Zhang, Hongyu. (2017). Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3 Signaling Pathway. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 18(2), 315.
MLA	Li, Zhengmao,et al."Valproate Attenuates Endoplasmic Reticulum Stress-Induced Apoptosis in SH-SY5Y Cells via the AKT/GSK3 Signaling Pathway".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 18.2(2017):315.