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Anion exchanger 2 mediates the action of arsenic trioxide.
Anion exchanger 2 ( AE2) mediates the exchange of C1-/HCO3- across the plasma membrane and plays a role in the regulation of intracellular pH. The present study showed that AE2 protein expression was upregulated immediately after exposure to either low (0.5 micromol/l) or high (1 and 2 micromol/l) concentrations of arsenic trioxide. This suggests that arsenic trioxide may act via regulation of intracellular pH. Changing the culture pH in NB4 cells modulated the degradation of promyelocytic leukaemia-retinoic acid receptor-alpha (PML-RARalpha), PML and RARalpha, which supported this hypothesis. DIDS (4,4'-diisothiocyanodihydrostilbene-2,2'-disulphonic acid) inhibited AE2 function, preventing the arsenic trioxide-induced degradation of RARalpha and low concentration showed synergistic effects on the expression of CD11c, which is related with cell differentiation. In addition, DIDS rescued the cells from 1 micromol/l arsenic trioxide-induced apoptosis. In conclusion, AE2 mediated the action of arsenic trioxide via regulation of intracellular pH and a novel pathway for the mechanism of action of arsenic trioxide is reported.[1]References
- Anion exchanger 2 mediates the action of arsenic trioxide. Pan, X.Y., Chen, G.Q., Cai, L., Buscemi, S., Fu, G.H. Br. J. Haematol. (2006) [Pubmed]
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