双萜化合物对FOXO3a核转位调控机制  

The Mechanism of FOXO3a Translocation by a Diterpenoid Compound

作　　者：刘金花[1] 朱玉山[1] 

机构地区：[1]南开大学生命科学学院,天津300071

出　　处：《南开大学学报（自然科学版）》2014年第6期35-39,共5页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：国家自然基金(31271529);973项目(2010CB912204)

摘　　要：从中国传统药用植物绣线菊中提取一种可以引起bax和bak非依赖性细胞凋亡的双萜类化合物,并将其命名为S3.前期的研究发现S3可引起bax-/-/bak-/-MEF细胞活性氧(ROS)水平显著升高,并激活FOXO3a,促进其从胞浆转位至细胞核.然而由S3介导产生的活性氧是如何激活FOXO3a转录因子的,目前仍不是很清楚.本研究发现S3诱导细胞凋亡过程中可以激活JNK、ERK信号通路,同时显著地抑制AKT的活性;而ROS的清除剂NAC有效地抑制JNK、ERK的激活,促进AKT的活化,同时抑制FOXO3a的核转位.从而证实由S3介导产生的活性氧通过调控JNK、ERK、AKT激酶的活性,进而调控FOXO3a的核转位活性.A natural diterpenoid compound,named as S3,a Chinese traditional medical plant which induced Bax and Bak-independent apoptosis.And previous study also found that this compound could induce the production of reactive oxygen species（ROS）,leading to the activation of FOXO3a.However,how the ROS generation induced by S3 activate FOXO3a is still unclear.Here,our study show that S3 could increase c-Jun NH2-terminal kinase1/2（JNK1/2）and extracellular signal-regulated kinase1/2（ERK1/2）activity and coincide with decreased AKT signaling;while pretreatment with NAC reverse JNK,ERK activation and AKT inhibition and abolish FOXO3a nuclear accumulation.Taken together,the data show the ROS generation in response to S3 regulates the translocation of FOXO3a dependent upon JNK、ERK、AKT activation.

关 键 词：活性氧 FOXO3a转录因子 JNK激酶 AKT激酶 

分 类 号：Q813[生物学—生物工程]