Pin1 Promotes Regulated Necrosis Induced by Glutamate in Rat Retinal Neurons via CAST/Calpain2 Pathway.
Pin1 Promotes Regulated Necrosis Induced by Glutamate in Rat Retinal Neurons via CAST/Calpain2 Pathway.
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Pin1 通过 CAST/Calpain2 途径促进谷氨酸诱导的大鼠视网膜神经元坏死
DOI：
10.3389/fncel.2017.00425
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发表时间：
2017
影响因子：
5.3
通讯作者：
Xiong K
中科院分区：
文献类型：
--
作者：
Wang S;Liao L;Wang M;Zhou H;Huang Y;Wang Z;Chen D;Ji D;Xia X;Wang Y;Liu F;Huang J;Xiong K
本研究的目的是探讨在过量谷氨酸条件下，肽基-脯氨酰顺式/转移酶NIMA相互作用1(Pin1)是否能与钙调蛋白(CAST)相互作用，调节CAST/Calkin2，进而调节视网膜神经元的坏死。碘化丙啶染色和乳酸脱氢酶实验表明，谷氨酸可触发原代培养的视网膜神经细胞CAST/CAP2介导的坏死调节。Co-IP结果和计算机模拟表明Pin1可以与CAST结合。Western印迹、实时定量聚合酶链式反应、免疫荧光和磷酸化分析结果表明Cast受Pin1调节，胡桃苷酮(即Pin1特异性抑制剂)的应用证实了这一点。然后利用视网膜神经节细胞株5，结合siRNA方法和流式细胞术，验证Pin1在谷氨酸诱导的CAST/Calkin2调制的神经元坏死中的调控途径。最后，在活体研究中，进一步证实了Pin1在谷氨酸刺激后的大鼠视网膜神经节细胞和内核层中，在CAST/Calkin2调制的坏死中所起的作用。此外，闪光视网膜电流图研究为胡桃酮治疗谷氨酸所致的视功能损害的恢复提供了证据。我们的工作旨在研究Pin1-Cast/Calkin2通路在谷氨酸介导的兴奋性毒性中的作用。
The purpose of the current study was to investigate whether peptidyl-prolylcis/transisomerase NIMA-interacting 1 (Pin1) can interact with calpastatin (CAST) and regulate CAST/calpain2, under excessive glutamate conditions, and subsequently regulate necrosis in rat retinal neurons. Glutamate triggered CAST/calpain2-mediated necrosis regulation in primary cultured retinal neurons, as demonstrated by propidium iodide-staining and lactate dehydrogenase assay. Co-IP results and a computer simulation suggested that Pin1 could bind to CAST. Western blot, real-time quantitative polymerase chain reaction, immunofluorescence, and phosphorylation analysis results demonstrated that CAST was regulated by Pin1, as proven by the application of juglone (i.e., a Pin1 specific inhibitor). The retinal ganglion cell 5 cell line, combined with siRNA approach and flow cytometry, was then used to verify the regulatory pathway of Pin1 in CAST/calpain2-modulated neuronal necrosis that was induced by glutamate. Finally,in vivostudies further confirmed the role of Pin1 in CAST/calpain2-modulated necrosis following glutamate excitation, in the rat retinal ganglion cell and inner nuclear layers. In addition, a flash electroretinogram study provided evidence for the recovery of impaired visual function, which was induced by glutamate, with juglone treatment. Our work aims to investigate the involvement of the Pin1-CAST/calpain2 pathway in glutamate-mediated excitotoxicity.
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影响因子：
3.7
作者：
Averna M;De Tullio R;Pedrazzi M;Bavestrello M;Pellegrini M;Salamino F;Pontremoli S;Melloni E
通讯作者：
Melloni E
影响因子：
14.9
作者：
Chao, SH;Greenleaf, AL;Price, DH
通讯作者：
Price, DH
DOI：
10.1016/j.bbrc.2005.08.130
发表时间：
2005-10-21
影响因子：
3.1
作者：
Akiyama, H;Shin, RW;Uchida, T
通讯作者：
Uchida, T
影响因子：
3
作者：
Driver, Jane A.;Zhou, Xiao Zhen;Lu, Kun Ping
通讯作者：
Lu, Kun Ping
影响因子：
5.3
作者：
Carnemolla A;Michelazzi S;Agostoni E
通讯作者：
Agostoni E