Smarcd1 antagonizes the apoptosis of injured MES23.5 DA cells by enhancing the effect of Six2 on GDNF expression
Smarcd1 antagonizes the apoptosis of injured MES23.5 DA cells by enhancing the effect of Six2 on GDNF expression
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Smarcd1通过增强Six2对GDNF表达的影响来拮抗受损MES23.5 DA细胞的凋亡
DOI：
10.1016/j.neulet.2021.136088
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发表时间：
2021-07
影响因子：
2.5
通讯作者：
Can-tang Zhang
中科院分区：
文献类型：
--
作者：
Jin Gao;Deng-li Qin;Chuan-xi Tang;Xiao-yu Kang;Cheng-jie Song;Can-tang Zhang
胶质细胞源性神经营养因子（GDNF）在多巴胺（DA）能神经元的存活和修复中起着重要作用。转录因子Six2可以通过促进GDNF的表达来修复损伤的DA细胞，但其分子机制尚不清楚。本研究采用液相色谱-电喷雾串联质谱（LC-ESI-ITMS/MS）技术，从6-OHDA处理的MES23.5 DA细胞中筛选出43个与Six2相互作用的蛋白质。Smarcd1是SWI/SNF染色质重塑复合物家族的成员。结果证实Smarcd1与Six2形成转录复合物，Smarcd1主要与GDNF启动子2840 bp-2933 bp区域结合。Smarcd1基因敲低可抑制Six2对GDNF表达的影响，导致受损DA神经元细胞存活率降低，凋亡增加，Smarcd1基因过表达的结果与Smarcd1基因敲低相反。总之，我们的研究结果表明，smarcd1可以招募到GDNF的启动子区的转录因子Six2，以促进GDNF表达的Six2的效果，并保护损伤的MES 23. 5 DA细胞，这可能是有用的，在确定潜在的药物靶点，促进内源性GDNF的表达。
Glial cell line-derived neurotrophic factor (GDNF) played critical roles in the survival and repair of dopaminergic (DA) neurons. Transcription factor Six2 could repair injured DA cells by promoting the expression of GDNF, however, the underlying molecular mechanisms remain largely unknown. In this study, we screened forty-three proteins that interacted with Six2 in MES23.5 DA cells treated with 6-OHDA by liquid chromatography - electrospray - ionization tandem mass spectrometry (LC-ESI-ITMS/MS). Among these proteins, Smarcd1 is a member of SWI/SNF chromatin-remodeling complex family. Our results confirmed that Smarcd1 formed a transcription complex with Six2, and Smarcd1 mainly binded to the 2840 bp-2933 bp region of the GDNF promoter. Furthermore, knockdown of Smarcd1 inhibited the effect of Six2 on GDNF expression, and resulted in decreased cell viability and increased the apoptosis of injured DA neurons, and the result of overexpression of Smarcd1 is opposite to knockdown. Taken together, our results indicate that smarcd1 can be recruited to the promoter region of GDNF by transcription factor Six2 to promote the effect of Six2 on GDNF expression and protect injured MES23.5 DA cells, which could be useful in identifying potential drug targets for promoting endogenous GDNF expression.
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影响因子：
12.4
作者：
Espinoza, Stefano;Scarpato, Margherita;Gustincich, Stefano
通讯作者：
Gustincich, Stefano
影响因子：
11.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
Bailey, MES
影响因子：
82.9
作者：
Gill, SS;Patel, NK;Heywood, P
通讯作者：
Heywood, P