Jiang Quan, Wu Gang, Yang Lin, Lu Ya-Ping, Liu Xiu-Xiu, Han Feng, Deng Ya-Ping, Fu Xu-Chun, Liu Qi-Bing, Lu Ying-Mei
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
School of Medicine, Zhejiang University City College, Hangzhou, China.
Cell Physiol Biochem. 2018;47(5):2018-2030. doi: 10.1159/000491470. Epub 2018 Jul 3.
BACKGROUND/AIMS: Peptidyl-prolyl cis-trans isomerase FKBP25 is a member of the FK506-binding proteins family which has peptidyl-prolyl cis/trans isomerase domain. The biological function and pathophysiologic role of FKBP25 remain elusive.
The spatio-temporal changes in expression of endothelial FKBP25 upon oxygen-glucose deprivation (OGD) treatment were examined by Western blot and immunofluorescence. The immunoprecipitation and fluorescence resonance energy transfer (FRET) were used to address the interacting proteins with FKBP25.
In the present study, nuclear translocation of FKBP25 was observed following OGD in cultured endothelial cells. Intriguingly, FKBP25 nuclear translocation was further validated in peroxynitrite (ONOO-)-treated endothelial cells. Coimmunoprecipitation and FRET data indicated that FKBP25 translocated into the nucleus, in which it interacted with 60S ribosomal protein L7a, while overexpression FKBP25 protect endothelial cells against OGD injury.
Our findings reveal that the nuclear import of FKBP25 and binding with 60S ribosomal protein L7a are protective stress responses to ischemia/nitrosaive stress injury.
背景/目的：肽基脯氨酰顺反异构酶FKBP25是FK506结合蛋白家族的成员，具有肽基脯氨酰顺/反异构酶结构域。FKBP25的生物学功能和病理生理作用仍不清楚。
通过蛋白质免疫印迹法和免疫荧光法检测氧糖剥夺（OGD）处理后内皮细胞中FKBP25表达的时空变化。采用免疫沉淀和荧光共振能量转移（FRET）技术研究与FKBP25相互作用的蛋白。
在本研究中，培养的内皮细胞经OGD处理后观察到FKBP25的核转位。有趣的是，在过氧亚硝酸盐（ONOO-）处理的内皮细胞中进一步验证了FKBP25的核转位。免疫共沉淀和FRET数据表明，FKBP25转位至细胞核并与60S核糖体蛋白L7a相互作用，而过表达FKBP25可保护内皮细胞免受OGD损伤。
我们的研究结果表明，FKBP25的核输入及其与60S核糖体蛋白L7a的结合是对缺血/亚硝化应激损伤的保护性应激反应。
