Allopregnanolone Modulates GABAAR-Dependent CaMKII delta 3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage

doi:10.3389/fncel.2019.00569

科研成果详情

题名	Allopregnanolone Modulates GABAAR-Dependent CaMKII delta 3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage
作者	Wang, Tongtong 1,2; Ye, Xin 1,2; Bian, Wei 1,2; Chen, Zhichi 1,2; Du, Juanjuan2,3; Li, Mengyi1,2; Zhou, Peng1,2; Cui, Huairui1,2; Ding, Yu-Qiang2; Qi, Shuangshuang4; Liao, Min2,3; Sun, Chenyou1,2
发表日期	2020-01-13
发表期刊	FRONTIERS IN CELLULAR NEUROSCIENCE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	allopregnanolone gamma-aminobutyric acid A receptor tyrosine hydroxylase-positive cell Ca2+ calmodulin-dependent protein kinase II delta 3 brain-derived neurotrophic factor SH-SY5Y neuronal cell line
其他关键词	NEUROTROPHIC FACTOR EXPRESSION ; GAMMA-AMINOBUTYRIC-ACID ; DOPAMINERGIC-NEURONS ; SUBSTANTIA-NIGRA ; KINASE-II ; PARKINSONS-DISEASE ; GABA(A) RECEPTORS ; NEUROSTEROID ALLOPREGNANOLONE ; NEUROACTIVE STEROIDS ; INTRACELLULAR CA2+
摘要	Allopregnanolone (AP alpha), as a functional neurosteroid, exhibits the neuroprotective effect on neurodegenerative diseases such as Parkinson's disease (PD) through gamma-aminobutyric acid A receptor (GABAAR), but it has not been completely understood about its molecular mechanisms. In order to investigate the neuroprotective effect of AP alpha, as well as to clarify its possible molecular mechanisms, SH-SY5Y neuronal cell lines were incubated with 6-hydroxydopamine (6-OHDA), which has been widely used as an in vitro model for PD, along with AP alpha alone or in combination with GABAAR antagonist (bicuculline, Bic), intracellular Ca2+ chelator (EGTA) and voltage-gated L-type Ca2+ channel blocker (Nifedipine). The viability, proliferation, and differentiation of SH-SY5Y cells, the expression levels of calmodulin (CaM), Ca2+/calmodulin-dependent protein kinase II delta 3 (CaMKII delta 3), cyclin-dependent kinase-1 (CDK1) and brain-derived neurotrophic factor (BDNF), as well as the interaction between CaMKII delta 3 and CDK1 or BDNF, were detected by morphological and molecular biological methodology. Our results found that the cell viability and the number of tyrosine hydroxylase (TH), bromodeoxyuridine (BrdU) and TH/BrdU-positive cells in 6-OHDA-treated SH-SY5Y cells were significantly decreased with the concomitant reduction in the expression levels of aforementioned proteins, which were ameliorated following AP alpha administration. In addition, Bic could further increase the number of TH or BrdU-positive cells as well as the expression levels of aforementioned proteins except for TH/BrdU-double positive cells, while EGTA and Nifedipine could attenuate the expression levels of CaM, CaMKII delta 3 and BDNF. Moreover, there existed a direct interaction between CaMKII delta 3 and CDK1 or BDNF. As a result, AP alpha-induced an increase in the number of TH-positive SH-SY5Y cells might be mediated through GABAAR via Ca2+/CaM/CaMKII delta 3/BDNF (CDK1) signaling pathway, which would ultimately facilitate to elucidate PD pathogenesis and hold a promise as an alternative therapeutic target for PD.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81671401]; Zhejiang Medical and Health Science and Technology Program of China [2016KYA133]; Wenzhou Public Welfare Science and Technology Project of China [Y20190059]; (Wenzhou Municipal Science and Technology Bureau); Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LY12C11003]
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1662-5102
EISSN	1662-5102
卷号	13 页码:569
DOI	10.3389/fncel.2019.00569
页数	21
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000509526000001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31998078
PMC记录号	PMC6970471
SCOPUSEID	2-s2.0-85078795411
通讯作者地址	[Sun, Chenyou]Wenzhou Med Univ, Sch Basic Med Sci, Dept Anat, Wenzhou, Peoples R China. ; [Liao, Min;Sun, Chenyou]Wenzhou Med Univ, Sch Basic Med Sci, Inst Neurosci, Wenzhou, Peoples R China. ; [Liao, Min]Wenzhou Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Wenzhou, Peoples R China.
引用统计	被引频次：7[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/13957
专题	基础医学院（机能实验教学中心）_形态学系_人体解剖学基础医学院（机能实验教学中心）附属第二医院基础医学院（机能实验教学中心）_形态学系_组织胚胎学
通讯作者	Liao, Min; Sun, Chenyou
作者单位	1.Wenzhou Med Univ, Sch Basic Med Sci, Dept Anat, Wenzhou, Peoples R China; 2.Wenzhou Med Univ, Sch Basic Med Sci, Inst Neurosci, Wenzhou, Peoples R China; 3.Wenzhou Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Wenzhou, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 2, Dept Pharm, Wenzhou, Peoples R China
第一作者单位	基础医学院（机能实验教学中心）_形态学系_人体解剖学; 基础医学院（机能实验教学中心）
通讯作者单位	基础医学院（机能实验教学中心）_形态学系_人体解剖学; 基础医学院（机能实验教学中心）; 基础医学院（机能实验教学中心）_形态学系_组织胚胎学
第一作者的第一单位	基础医学院（机能实验教学中心）_形态学系_人体解剖学
推荐引用方式 GB/T 7714	Wang, Tongtong,Ye, Xin,Bian, Wei,et al. Allopregnanolone Modulates GABAAR-Dependent CaMKII delta 3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage[J]. FRONTIERS IN CELLULAR NEUROSCIENCE,2020,13:569.
APA	Wang, Tongtong., Ye, Xin., Bian, Wei., Chen, Zhichi., Du, Juanjuan., ... & Sun, Chenyou. (2020). Allopregnanolone Modulates GABAAR-Dependent CaMKII delta 3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage. FRONTIERS IN CELLULAR NEUROSCIENCE, 13, 569.
MLA	Wang, Tongtong,et al."Allopregnanolone Modulates GABAAR-Dependent CaMKII delta 3 and BDNF to Protect SH-SY5Y Cells Against 6-OHDA-Induced Damage".FRONTIERS IN CELLULAR NEUROSCIENCE 13(2020):569.