Thyroid hormone stimulates Na-K-ATPase activity and its plasma membrane insertion in rat alveolar epithelial cells

Jianxun Lei, Sogol Nowbar, Cary N. Mariash, David H. Ingbar

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46 Scopus citations


Na-K-ATPase protein is critical for maintaining cellular ion gradients and volume and for trans-epithelial ion transport in kidney and lung. Thyroid hormone, 3,3′,5-triiodo-L-thyronine (T3), given for 2 days to adult rats, increases alveolar fluid resorption by 65%, but the mechanism is undefined. We tested the hypothesis that T3 stimulates Na-K-ATPase in adult rat alveolar epithelial cells (AEC), including primary rat alveolar type II (ATII) cells, and determined mechanisms of the T3 effect on the Na-K-ATPase enzyme using two adult rat AEC cell lines (MP48 and RLE-6TN). T3 at 10-8 and 10-5 M increased significantly hydrolytic activity of Na-K-ATPase in primary ATII cells and both AEC cell lines. The increased activity was dose dependent in the cell lines (10 -9-10-4 M) and was detected within 30 min and peaked at 6 h. Maximal increases in Na-K-ATPase activity were twofold in MP48 and RLE-6TN cells at pharmacological T3 of 10-5 and 10-4 M, respectively, but increases were statistically significant at physiological T3 as low as 10-9 M. This effect was T3 specific, because reverse T3 (3,3′,5′-triiodo-L-thyronine) at 10-9-10-4 M had no effect. The T3-induced increase in Na-K-ATPase hydrolytic activity was not blocked by actinomycin D. No significant change in mRNA and total cell protein levels of Na-K-ATPase were detected with 10 -9-10-5 M T3 at 6 h. However, T3 increased cell surface expression of Na-K-ATPase α1- or β1-subunit proteins by 1.7- and 2-fold, respectively, and increases in Na-K-ATPase activity and cell surface expression were abolished by brefeldin A. These data indicate that T3 specifically stimulates Na-K-ATPase activity in adult rat AEC. The upregulation involves translocation of Na-K-ATPase to plasma membrane, not increased gene transcription. These results suggest a novel nontranscriptional mechanism for regulation of Na-K-ATPase by thyroid hormone.

Original languageEnglish (US)
Pages (from-to)L762-L772
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 29-3
StatePublished - Sep 1 2003


  • Alveolar cell lines
  • Protein translocation
  • Sodium pump


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