The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation.
Article Details
- CitationCopy to clipboard
Wang ZX, Jiang CS, Liu L, Wang XH, Jin HJ, Wu Q, Chen Q
The role of Akt on arsenic trioxide suppression of 3T3-L1 preadipocyte differentiation.
Cell Res. 2005 May;15(5):379-86.
- PubMed ID
- 15916724 [ View in PubMed]
- 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 PPARgamma and C/EBPalpha and disrupting the interaction between PPARgamma and RXRalpha, 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 PPARgamma . 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.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Arsenic trioxide RAC-alpha serine/threonine-protein kinase Protein Humans UnknownInducerDetails