The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte dif-ferentiation  

作　　者：ZhiXinWANG ChunSunJIANG LeiLIU XiaoHuiWANG HaiJingJIN QiaoWU QuanCHEN 

机构地区：[1]StateKeyLaboratoryofBiomembraneandMembraneBiotechnology,InstituteofZoology,ChineseAcademyofSciences,Beijing100080,China [2]CollegeoflifeScience,XiamenUniversity,Xiamen361005,China

出　　处：《Cell Research》2005年第5期379-386,共8页细胞研究（英文版）

基　　金：This work is supported by grants from National Nature Science Foundation of China(No.30000083);Quan.CHEN's laboratory was supported by grants“Knowledge Innovation Key Project"(kscx2-sw-2010)of Chinese Academy of Sciences;the National Basic Research Program of China(973 program project,No.2002CB5 13 100);National Fund for Outstanding Young Scholars from NSFC(30325013)awarded to Quan CHEN.

摘　　要：The present study investigates the molecular details of how arsenic trioxide inhibits preadipocyte differentiation and examines the role of Akt/PKB in regulation of differentiation and apoptosis. Continual exposure of arsenic trioxide, at the clinic achievable dosage that does not induce apoptosis, suppressed 3T3-L1 cell differentiation into fat cells by inhibiting the expression of PPARγ and C/EBPα and disrupting the interaction between PPARγ and RXRα, which determines the programming of the adipogenic genes. Interestingly, if we treated the cells for 12 or 24 h and then withdrew arsenic trioxide, the cells were able to differentiate to the comparable levels of untreated cells as assayed by the activity of GAPDH, the biochemical marker of preadipocyte differentiation. Long term treatment blocked the differentiation and the activity of GAPDH could not recover to the comparable levels of untreated cells. Continual exposure of arsenic trioxide caused accumulation in G2/M phase and the accumulation of p21. We found that arsenic trioxide induced the expression and the phosphorylation of Akt/PKB and it inhibited the interaction between Akt/PKB and PPARγ . Akt/PKB inhibitor appears to block the arsenic trioxide suppression of differentiation. Our results suggested that Akt/PKB may play a role in suppression of apoptosis and negatively regulate preadipocyte differentiation.

关 键 词：PREADIPOCYTE cell differentiation apoptosis AKT/PKB Arsenic trioxide. 

分 类 号：Q254[生物学—细胞生物学] Q255