PT -期刊文章盟Shau-Yu刘盟-马Yun-Li盟Hsiao-Yuan李TI -淀粉样β蛋白诱导PIAS1 ser - 503磷酸化和Elk-1 SUMOylation调节内源性神经保护与淀粉样β蛋白毒性(P2.188) DP - 2018年4月10 TA -神经病学PG - P2.188 VI - 90 IP - 15补充4099 - //www.ez-admanager.com/content/90/15_Supplement/P2.188.short 4100 - http://n.neu首页rology.org/content/90/15_Supplement/P2.188.full所以Neurology2018 4月10;90 AB -目的:调查的内生防御机制被激活在急性淀粉样β蛋白的侮辱。背景:蛋白质抑制剂激活STAT1 (PIAS1)最初被确定为一个抑制剂STAT1的先天免疫反应中起着重要的作用。PIAS1磷酸化在ser - 90被发现在回应各种炎症刺激和调节NF-kB和STAT1-mediated基因表达。此外,PIAS1拥有小ubiquitin-like修饰符(相扑)作为一个相扑E3连接酶活性和功能。但PIAS1是否也在其他残留物和磷酸化PIAS1磷酸化在其他残留如何影响其E3连接酶活性和生理功能是不知道。设计/方法:LC /质量,在体外和体内实验研究小说磷酸化PIAS1网站。老鼠和SUMOylation试验使用,本研究采用免疫印迹和定量rt - pcr。结果:我们发现PIAS1可以通过MAPK / ERK的磷酸化在ser - 503体外和鼠海马。PIAS1磷酸化在ser - 503增加了相扑E3连接酶在大鼠海马的活动。此外,转录因子可以SUMO-modified Elk-1 PIAS1和封锁PIAS1磷酸化在ser - 503减少Elk-1 SUMOylation鼠海马。 In further experiments, we found that acute amyloid-beta injection to rat CA1 area increases PIAS1 phosphorylation at Ser-503 and Elk-1 SUMOylation. Moreover, blockade of Elk-1 SUMOylation increases Elk-1 phosphorylation at Ser-383 and its transcriptional activity, and increases the expression of the apoptotic gene GADD45alpha.Conclusions: Amyloid-beta is known to produce neurotoxicity to neurons, but the endogenous defense mechanism that is activated by amyloid-beta is less well known. Our results suggest that acute amyloid-beta induces PIAS1 phosphorylation at Ser-503 and enhances Elk-1 SUMOylation that consequently decreases the expression of GADD45alpha. This novel signaling pathway may serve as an endogenous neuroprotection mechanism against amyloid-beta toxicity.Disclosure: Dr. Liu has nothing to disclose. Dr. Ma has nothing to disclose. Dr. Lee has nothing to disclose.