title: Aqp1 expression in erythroleukemia cells: genetic regulation of glucocorticoid and chemical induction.
abstract: The aquaporin-1 (AQP1) water channel protein is expressed in multiple mammalian tissues by several different developmental programs; however, the genetic regulation is undefined. The proximal promoter of mouse Aqp1 contains multiple putative cis-acting regulatory elements, and mouse erythroleukemia (MEL) cells are a well-characterized model for erythroid differentiation. Corticosteroid or dimethyl sulfoxide (DMSO) exposure induces AQP1 protein expression in MEL cells, and transcriptional regulation was investigated by transient transfections with Aqp1 promoter-reporter constructs. Dexamethasone induction is abrogated by deletion of two glucocorticoid response elements -0.5 kilobases (kb) from the transcription initiation site. Mutation of the GATA element at -0.62 kb has no effect, whereas mutation of the CACCC site at -37 bp significantly reduces DMSO-induced promoter activity. Hydroxyurea induces expression of AQP1 protein without acting through the proximal promoter. The MEL cell line is a reproducible erythroid model system for studying transcriptional regulation of the Aqp1 gene while determining the consequences on AQP1 protein biosynthesis.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
authors.forename: C
authors.initials: C
authors.lastname: Moon
authors.forename: L S
authors.initials: LS
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Agre
mesh_terms: D000818:Animals; D051398:Aquaporin 1; D020346:Aquaporins; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D005796:Genes; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology; D007473:Ion Channels / Q000096:biosynthesis*; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D017384:Sequence Deletion; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C496021:Aqp1 protein, mouse; D020346:Aquaporins; D005938:Glucocorticoids; D007473:Ion Channels; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D051398:Aquaporin 1; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D004121:Dimethyl Sulfoxide