ABSTRACT
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.
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Acknowledgements
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, and the National Basic Research Program of China (973 program project, No.2002CB513100) and National Fund for Outstanding Young Scholars from NSFC (30325013) awarded to Quan CHEN.
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WANG, Z., JIANG, C., LIU, L. et al. The role of Akt on Arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation. Cell Res 15, 379–386 (2005). https://doi.org/10.1038/sj.cr.7290305
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DOI: https://doi.org/10.1038/sj.cr.7290305
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