Tang Lan, Zhang Yanke, Chen Guojun, Xiong Yan, Wang Xuefeng, Zhu Binglin
The Public Health Center, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, China.
Neurochem Res. 2017 Apr;42(4):1211-1218. doi: 10.1007/s11064-016-2158-8. Epub 2017 Feb 27.
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a unique PPIase belonging to the parvulin family, and it isomerizes peptide bond between phospho-(Ser/Thr) and Pro. Pin1 has been linked to the pathogenesis of various human diseases; however, its exact biological functions remain unclear. The aim of the present study is to explore the expression pattern of Pin1 in patients with refractory epilepsy and in a chronic pilocarpine-induced epileptic mouse model. Using Western blot, immunofluorescence and immunoprecipitation analysis, we found that Pin1 protein was mainly distributed in neurons, demonstrated by colocalization with the dendritic marker, MAP2. However, the expression of Pin1 decreased remarkably in epileptic patients and experimental mice. Furthermore, the reciprocal coimmunoprecipitation analysis showed that Pin1 interacted with NR2A and NR2B-containing NMDA receptors not AMPA receptors in epileptic mouse models. Our results are the first to indicate that the expression of Pin1 in epileptic brain tissue could play important roles in epilepsy.
肽基脯氨酰顺反异构酶NIMA相互作用蛋白1（Pin1）是一种属于小菌素家族的独特肽脯氨酰顺反异构酶，它使磷酸化（丝氨酸/苏氨酸）与脯氨酸之间的肽键发生异构化。Pin1与多种人类疾病的发病机制有关；然而，其确切的生物学功能仍不清楚。本研究的目的是探讨Pin1在难治性癫痫患者和慢性毛果芸香碱诱导的癫痫小鼠模型中的表达模式。通过蛋白质免疫印迹、免疫荧光和免疫沉淀分析，我们发现Pin1蛋白主要分布在神经元中，这通过与树突标记物微管相关蛋白2（MAP2）共定位得以证明。然而，Pin1在癫痫患者和实验小鼠中的表达显著降低。此外，相互免疫共沉淀分析表明，在癫痫小鼠模型中，Pin1与含NR2A和NR2B的N-甲基-D-天冬氨酸（NMDA）受体相互作用，而不是与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体相互作用。我们的结果首次表明，Pin1在癫痫脑组织中的表达可能在癫痫中起重要作用。
