Thyroid hormone rapidly stimulates alveolar Na,K-ATPase by activation of phosphatidylinositol 3-kinase.
OBJECTIVE
Nongenomic actions of 3,3',5-triiodo-L-thyronine (T3) occur quite rapidly usually via activation of signaling cascades. In this review, we focus on recent advances made in the understanding of activation of the phosphatidylinositol 3-kinase pathway by T3 in alveolar epithelial cells, resulting in upregulation of Na,K-ATPase hydrolytic activity and potential physiological significance of this finding.


RESULTS
T3 stimulates the Src family of kinases. Activation of Src-kinase and phosphatidylinositol 3-kinase/protein kinase B is required for the T3-induced stimulation of alveolar epithelial Na,K-ATPase activity in rat alveolar epithelial cells. The stimulation does not require transcription. This T3-sensitive Na,K-ATPase stimulation in rat alveolar epithelial cells is switched on late in gestation. In skin fibroblasts phosphatidylinositol 3-kinase is also involved in the nongenomic T3 stimulation of ZAK1-4alpha protein expression, an endogenous calcineurin inhibitor.


CONCLUSIONS
T3 plays an important role in cell survival and differentiation. Nongenomic regulation of phosphatidylinositol 3-kinase and downstream molecules by T3 is being recognized in different tissues. Upregulation of alveolar Na,K-ATPase is one such molecule, which plays an important role in removal of edema fluid from the alveolar space. These effects are rapid and do not require direct nuclear gene transcription.
Bhargava
Maneesh
M
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota Medical Centre, Minneapolis, Minnesota, USA.
Lei
Jianxun
J
Mariash
Cary N
CN
Ingbar
David H
DH
D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D038081:Organogenesis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000201:enzymology*; D051381:Rats; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism
D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000254:Sodium-Potassium-Exchanging ATPase; D014284:Triiodothyronine; D019061:src-Family Kinases