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Am J Physiol Lung Cell Mol Physiol 294: L749-L754, 2008. First published January 25, 2008; doi:10.1152/ajplung.00335.2007
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T3 increases Na-K-ATPase activity via a MAPK/ERK1/2-dependent pathway in rat adult alveolar epithelial cells

Jianxun Lei,1 Cary N. Mariash,1 Maneesh Bhargava,1 Elizabeth V. Wattenberg,2 and David H. Ingbar1

Departments of 1Medicine, Medical School, and 2Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, Minnesota

Submitted 20 August 2007 ; accepted in final form 22 January 2008

Thyroid hormone (T3) increases Na-K-ATPase activity in rat adult alveolar type II cells via a PI3K-dependent pathway. In these cells, dopamine and β-adrenergic agonists can stimulate Na-K-ATPase activity through either PI3K or MAPK pathways. We assessed the role of the MAPK pathway in the stimulation of Na-K-ATPase by T3. In the adult rat alveolar type II-like cell line MP48, T3 enhanced MAPK/ERK1/2 activity in a dose-dependent manner. Increased ERK1/2 phosphorylation was observed within 5 min, peaked at 20 min, and then decreased. Two MEK1/2 inhibitors, U0126 and PD-98059, each abolished the T3-induced increase in the quantity of Na-K-ATPase {alpha}1-subunit plasma membrane protein and Na-K-ATPase activity. T3 also increased the phosphorylation of MAPK/p38; however, SB-203580, a specific inhibitor of MAPK/p38 activity, did not prevent the T3-induced Na-K-ATPase activity. SP-600125, a specific inhibitor of the MAPK/JNK pathway, also did not block the T3-induced Na-K-ATPase activity. Phorbol 12-myristate 13-acetate (PMA) significantly increased ERK1/2 phosphorylation and Na-K-ATPase activity. The PMA-induced Na-K-ATPase activity was inhibited by U0126. These data indicate that activation of MAPK-ERK1/2 was required for the T3-induced increase in Na-K-ATPase activity in addition to the requirement for the PI3K pathway.

thyroid hormone


Address for reprint requests and other correspondence: D. H. Ingbar, Pulmonary, Allergy, Critical Care, and Sleep Division, Univ. of Minnesota, MMC 276, 420 Delaware St. SE, Minneapolis, MN 55455 (e-mail: ingba001{at}umn.edu)




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