Na⁺-K⁺-ATPase gene regulation by glucocorticoids in a fetal lung epithelial cell line

Abstract

The Na+pump, Na+-K+-ATPase, along with the Na+ channel is essential for the removal of alveolar solute and fluid perinatally. Because Na+-pump mRNA and activity increase before birth and maternal glucocorticoids (GCs) influence Na+-K+-ATPase mRNA expression in fetal rat lung, we hypothesized that GCs increased Na+-K+-ATPase gene expression in a fetal lung epithelial cell line. After 24 h of exposure, dexamethasone increased the steady-state levels of Na+-K+-ATPase α1 and β1 mRNA in a fetal rat lung epithelial cell line in a dose-dependent fashion (10−7 to 10−5 M). The maximal increase in mRNA levels was 3.8-fold for α1 and 2.8-fold for β1. The increase in mRNA was detected as early as 6 h for the β1-subunit and 18 h for the α1-subunit, and both peaked at 24 h. This gene upregulation was not due to increased mRNA stability based on mRNA half-life determination after actinomycin D inhibition. Transfection experiments with α1and β1 promoter-reporter constructs demonstrated 3.2 ± 0.5- and 2.6 ± 0.4-fold increases, respectively, in promoter activity, consistent with transcriptional activation of the promoter-reporter construct. These findings, increased promoter activity with no change in stability, indicate that GCs increased Na+-K+-ATPase transcription in a fetal lung epithelial cell line.

Effect of dexamethasone on voltage-gated Na+ channel in cultured human bronchial smooth muscle cells

“…Glucocorticoids are the most effective therapy currently available for the treatment of asthma, and have been reported to affect ionic channels and then the electrical activity of excitable cells by regulating the transcription (Takimoto et al, 1993;Takimoto and Levitan, 1994;Chalaka et al, 1999). Glucocorticoids have been known to affect the expression of Na + -K + ATPase (Chalaka et al, 1999) and several ion channels such as K V 1.5, a non-inactivating K + current (Takimoto et al, 1993;Takimoto and Levitan, 1994).…”

“…Glucocorticoids have been known to affect the expression of Na + -K + ATPase (Chalaka et al, 1999) and several ion channels such as K V 1.5, a non-inactivating K + current (Takimoto et al, 1993;Takimoto and Levitan, 1994). Dexamethasone has been also reported to downregulate voltage-gated Na + channel in clonal rat pituitary cells, by using patch-clamp techniques, and saxitoxin binding assay (Avila et al, 2003).…”

“…Glucocorticoids have been known to affect Na + -K + ATPase (Chalaka et al, 1999) and several ion channels such as K V 1.5, a non-inactivating K + current (Takimoto et al, 1993;Takimoto and Levitan, 1994). The voltage-gated Na + channel (I Na ) exists in a wide variety of excitable cells including nerves, heart and skeletal muscle.…”

Up-regulation of Na,K-ATPase β1 Transcription by Hyperoxia Is Mediated by SP1/SP3 Binding

“…The sodium pump consists of two subunits, ␣ and ␤, which are necessary for normal enzyme activity. In some tissues, such as the lung, overexpression or up-regulation of the ␤ subunit results in increased activity, whereas, this is not true for the ␣ subunit (5,6). This implies that the ␤ subunit is the rate-limiting subunit.…”

Low Pulmonary Expression of Epithelial Na⁺ Channel and Na⁺, K⁺-ATPase in Newborn Infants with Congenital Diaphragmatic Hernia

“…It is well known that the expression of ENaC, Na + , K + -ATPase and AQP5 is affected by steroid administration [14,15,[46][47][48] . It has long been debated if antenatal glucocorticoid treatment could benefit CDH patients.…”