TY -的T1 -肾上腺受体ACTH1-39可以保护少突神经胶质通过抑制蛋白激酶C (P5.287) JF -神经学乔-神经学六世- 86 - 16补充SP P5.287 AU -罗伯特Lisak盟Liljana Nedelkoska AU -乔首页伊斯本杰明一起珍藏的东西Y1 - 2016/04/05 UR - //www.ez-admanager.com/content/86/16_Supplement/P5.287.abstract N2 -目的:识别激酶通路由ACTH1-39保护少突神经胶质(OL)死亡的细胞凋亡,会引起炎症介质或活性氧(ROS)。背景:髓鞘损伤和OL多发性硬化症涉及会引起,神经炎症和氧化应激。OL表达肾上腺受体;保护OL的肾上腺皮质ACTH1-39行为独立于糖皮质激素在体外从staurosporine引起的死亡,会引起,喹啉酸或ROS,但不是一氧化氮或犬尿酸(本杰明一起珍藏的东西et al . 2013年)。激酶信号通路激活ACTH1-39保护OL是未知的。方法:鼠OL孵化24小时ACTH和每个有毒的代理,有/无抑制剂PKCα,β,PI3激酶,腺苷酸环化酶或MAP激酶。控制包括媒介、毒剂或毒性药物加抑制剂。结果:抑制PKCα,β没有阻止或增强ACTH1-39保护。PKCα,然而,像ACTH1-39β抑制就足以保护OL的侮辱除了一氧化氮和犬尿酸。从staurosporine PI3激酶信号ACTH1-39保护OL,谷氨酸,门冬氨酸,kainate和喹啉酸。 Adenyl cyclase and MAP kinase are also utilized for OL protection from staurosporine, glutamate and quinolinic acid. Neither pathway is utilized for protection from AMPA or H2O2. Conclusions: Both ACTH1-39 and PKCα,β inhibition protect OL from the same insults, suggesting that those toxic agents all require PKCα,β activity for OL death, and that ACTH1-39 downregulates melanocortin receptor-coupled Gaq signaling to inhibit the PKC pathway. ACTH1-39 activates PI3 kinase, MAP kinase and/or adenyl cyclase to protect OL from some but not all of the toxic agents. In conclusion, ACTH1-39 and PKCα,β inhibition have a broader spectrum of OL protection than activation of PI3 kinase or MAP kinase. Support: Investigator Initiated Research Award from Mallinckrodt Pharmaceuticals Autoimmune/Rare Diseases Division (formerly Questcor); Parker Webber Chair in Neurology (DMC Foundation/WSU) (RL). Disclosure: Dr. Lisak has received personal compensation for activities with Teva, Mallinckrodt, and Syntimmune. Dr. Lisak has received research support from: Mallinckrodt, Teva, Sanofi, MedImmune, and Biogen Idec. Dr. Nedelkosk has received research support from Mallinckrodt. Dr. Benjamins has received research support from Questcor and Avanir Pharmaceuticals.Wednesday, April 20 2016, 8:30 am-7:00 pm ER -