title: As2O3 enhances the anion transport activity of band 3 and the action is related with the C-terminal 16 residues of the protein.
abstract: Successful application of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) has been attracting worldwide interest, but the exact mechanism for the action of As2O3 remains somewhat obscure. In the present work, we show for the first time that As2O3 facilitates the DIDS-sensitive anion transport activity of band 3 protein in red blood cells (RBCs) isolated from normal adults and APL patients. To elucidate the effect of As2O3 on band 3 protein, constructs encoding the full length of the band 3 transmembrane domain (mdb3) and its C-terminal deletion forms were transfected into yeast cells by a yeast display system. The results demonstrate that deletion of the C-terminal 16 residues of mdb3 (mdb3-d16) does not affect anion transport activity of mdb3 or its sensitivity to DIDS, but decreases its sensitivity to As2O3 in the yeast cell. More intriguingly, the forced expression of intact mdb3 by transfection significantly induces cell apoptosis in HeLa cells, to a higher degree than in cells transfected with mdb3-d16 or empty vector. Expression of activated caspase 3 in HeLa cells also indicates that the C-terminal 16 residues are important for mdb3-mediated apoptosis in cells treated with As2O3. Our results provide the first evidence that As2O3 enhances the anion transport activity of band 3 and the action is related with the C-terminal 16 residues of the protein.
authors.affiliation: Department of Pathophysiology, Rui-Jin Hospital, Shanghai Second Medical University (SSMU), Shanghai 200025, China. fuguhu@263.net
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Fu
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Xi
authors.forename: Zhuo-Wei
authors.initials: ZW
authors.lastname: Guo
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Liu
authors.forename: Shu-Zhi
authors.initials: SZ
authors.lastname: Bai
authors.forename: Bao-Feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Chen
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000328:Adult; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy*; D008297:Male; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D014162:Transfection; D015003:Yeasts / Q000235:genetics
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D000077237:Arsenic Trioxide