广东医学2012，Vol.33Issue(5)：575-578,4.
神经生长因子对PC12细胞内源性FoxO3a亚细胞分布的影响及其作用机制
Effect and mechanisms of nerve growth factor on the subcellular location of FoxO3a transcription factor in PC12 cells
摘要
Abstract
Objective To investigate the role of nerve growth factor ( NGF ) on the nuclear/plasma shuttling of FoxO3a. Methods PC12 cells were divided into serum - free group, serum free plus TrkA specific inhibitor K252a group, NGF-treated group, and NGF plus K252a group. Immunocytochemistry ( ICC ) with anti - FoxO3a antibody was applied to observe the subcellular location of endogenous FoxO3a. Overexpression of FoxO3a - green fluorescent protein was performed to confirm the ICC results. Western blot was used to analyze the phosphorylation of TrkA, Akt, MAPK and FoxO3a before or after the treatment of NGF and K252a. The PDK inhibitor LY294002, Akt inhibitorⅧ and ERK inhibitor were applied to study the underlying mechanisms. Results Endogenous FoxO3a was mainly located in the nucleus in serum-free condition and K252a - treated groups. FoxO3a was translocated to cytoplasma when PC12 cells were treated with NGF, which was blocked with K252a. Compared with serum - free group, NGF significantly induced phosphorylation of TrkA, Akt and FoxO3a, which was also blocked by K252a. Moreover, the phosphorylation of FoxO3a was blocked by PDK inhibitor LY294002 and Akt inhibitor Ⅷ, though the MAPK pathway inhibitor PD98059 showed no effect. Conclusion NGF promotes endogenous FoxO3a translocation to cytoplasma, and this effect may be related with the phosphorylation of TrkA and its downstream molecular induced by NGF.关键词
FoxO3a/磷酸化/核转位/神经生长因子Key words
FoxO3a/phosphorylation/translocation/nerve growth factor引用本文复制引用
段小鹿,汪海涛,廖素芬,黄健初,张浪,谭小燕,郑文华..神经生长因子对PC12细胞内源性FoxO3a亚细胞分布的影响及其作用机制[J].广东医学,2012,33(5):575-578,4.基金项目
国家自然科学基金资助项目(编号:30670652、30711120565、30970935),广东省科技计划项目(编号:2009B060700008),国家外专局外国文教专家重点项目(编号:36000-1181102),广东省外国专家局资助项目(编号:36000-5220001) （编号:30670652、30711120565、30970935）
