Wendt C H, Sharma R, Bair R, Towle H, Ingbar D H
Department of Medicine, University of Minnesota School of Medicine, Minneapolis, USA.
Environ Health Perspect. 1998 Oct;106 Suppl 5(Suppl 5):1213-7. doi: 10.1289/ehp.98106s51213.
The lung epithelium resorbs alveolar fluid through combined action of sodium channels and the sodium pump, Na,K-ATPase. The lung often is exposed to hyperoxia in disease states and hyperoxia generates a mixture of reactive oxygen species. In vivo and in vitro exposure of rat lung and alveolar type II cells, respectively, increases gene expression of both alpha-1 and beta-1 subunits of the sodium pump. In contrast to the primary type II cells, several type II cell lines did not increase sodium pump gene expression with hyperoxia, but the renal tubular epithelial MDCK cell line did. Using promoter-receptor constructs transfected into MDCK cells, hyperoxia did not markedly increase transcription of the alpha-1 subunit but doubled transcription of the beta-1 subunit gene. Using 5'-deletion constructs, the region required for the beta-1 increase was localized to a 40-base pair region from -44/-84. The hyperoxic responsiveness of this region was confirmed using constructs with one or two copies of this region placed in minimal promoter-luciferase reporters. This 5' promoter region contains a consensus binding sequence for SP-1, a basal transcription factor but not for binding of other known transcription factors. Thus, hyperoxia induces Na,K-ATPase beta-1 promoter transcription, likely acting through a novel mechanism.
肺上皮细胞通过钠通道和钠泵（Na，K - ATP酶）的联合作用重吸收肺泡液。在疾病状态下，肺常常暴露于高氧环境中，高氧会产生活性氧混合物。分别在体内和体外使大鼠肺和肺泡II型细胞暴露于高氧环境中，会增加钠泵α - 1和β - 1亚基的基因表达。与原代II型细胞不同，几种II型细胞系在高氧环境下不会增加钠泵基因表达，但肾小管上皮MDCK细胞系会。将启动子 - 受体构建体转染到MDCK细胞中，高氧不会显著增加α - 1亚基的转录，但会使β - 1亚基基因的转录增加一倍。使用5' - 缺失构建体，β - 1亚基增加所需的区域定位在 - 44 / - 84的40个碱基对区域。使用含有该区域一或两个拷贝的构建体置于最小启动子 - 荧光素酶报告基因中，证实了该区域对高氧的反应性。这个5'启动子区域包含SP - 1（一种基础转录因子）的共有结合序列，但不包含其他已知转录因子的结合序列。因此，高氧诱导Na，K - ATP酶β - 1启动子转录，可能通过一种新机制起作用。
