IngentaConnect Anion exchanger 2 mediates the action of arsenic trioxide

Authors: Pan, Xiao-Yan¹; Chen, Guo-Qiang¹; Cai, Li²; Buscemi, Stephen³; Fu, Guo-Hui¹

Source: British Journal of Haematology, Volume 134, Number 5, September 2006 , pp. 491-499(9)

Abstract:

Summary

Anion exchanger 2 (AE2) mediates the exchange of Cl⁻/HCO 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 μmol/l) or high (1 and 2 μmol/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-RARα), PML and RARα, which supported this hypothesis. DIDS (4,4′-diisothiocyanodihydrostilbene-2,2′-disulphonic acid) inhibited AE2 function, preventing the arsenic trioxide-induced degradation of RARα 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 μmol/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.

Keywords: anion exchanger 2; arsenic trioxide; apoptosis; differentiation; anion exchange activity

Document Type: Research article

DOI: 10.1111/j.1365-2141.2006.06224.x

Affiliations: 1: Department of Pathophysiology, Shanghai Jiao Tong University, School of Medicine; Key Lab. of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Rui-Jin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, Chin 2: Department of Medicine, The Tumour Hospital of Harbin Medical University, Harbin, China 3: College of Nursing, University of Arizona, Tucson, AZ, USA

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