AQP1 EXPRESSION IN ERYTHROLEUKEMIA-CELLS - GENETIC-REGULATION OF GLUCOCORTICOID AND CHEMICAL INDUCTION

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 mo use erythroleukemia (MEL) cells are a well-characterized model for ery throid differentiation. Corticosteroid or dimethyl sulfoxide (DMSO) ex posure induces AQP1 protein expression in MEL cells, and transcription al regulation was investigated by transient transfections with Aqp1 pr omoter-reporter constructs. Dexamethasone induction is abrogated by de letion of two glucocorticoid response elements -0.5 kilobases (kb) fro m 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 si gnificantly reduces DMSO-induced promoter activity. Hydroxyurea induce s expression of AQP1 protein without acting through the proximal promo ter. The MEL cell line is a reproducible erythroid model system for st udying transcriptional regulation of the Aqp1 gene while determining t he consequences on AQP1 protein biosynthesis.