Aqp1 expression in erythroleukemia cells: genetic regulation of glucocorticoid and chemical induction
Aqp1 expression in erythroleukemia cells: genetic regulation of glucocorticoid and chemical induction
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DOI：
10.1152/ajpcell.1997.273.5.c1562
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发表时间：
1997-11-01
影响因子：
5.5
通讯作者：
Agre, P
中科院分区：
文献类型：
--
作者：
Moon, C;King, LS;Agre, P
水通道蛋白-1(Aquaporin-1，AQP1)通过多种不同的发育过程在多种哺乳动物组织中表达，但其遗传调控尚不明确。小鼠AQP1启动子近端含有多种顺式作用调控元件，小鼠红白血病(Mel)细胞是红系分化的典型模型。糖皮质激素或二甲基亚砜(DMSO)可诱导MEL细胞AQP1蛋白的表达，并通过瞬时转染AQP1启动子-报告载体研究其转录调控作用。地塞米松的诱导作用可通过从转录起始点删除两个糖皮质激素反应元件0.5kb而取消。GATA元件在-0.62kb的突变没有影响，而CACCC位点在-37bp的突变显著降低了DMSO诱导的启动子活性。羟基脲不通过近端启动子诱导AQP1蛋白的表达。MEL细胞系是一个可复制的红系模型系统，用于研究AQP1基因的转录调控，同时确定对AQP1蛋白生物合成的影响。
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.