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Protein kinase A-I? regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO(2) concentrations.


ABSTRACT: Elevated concentrations of CO2 (hypercapnia) lead to alveolar epithelial dysfunction by promoting Na,K-ATPase endocytosis. In the present report, we investigated whether the CO2/HCO3(-) activated soluble adenylyl cyclase (sAC) regulates this process. We found that hypercapnia increased the production of cyclic adenosine monophosphate (cAMP) and stimulated protein kinase A (PKA) activity via sAC, which was necessary for Na,K-ATPase endocytosis. During hypercapnia, cAMP was mainly produced in specific microdomains in the proximity of the plasma membrane, leading to PKA Type I? activation. In alveolar epithelial cells exposed to high CO2 concentrations, PKA Type I? regulated the time-dependent phosphorylation of the actin cytoskeleton component ?-adducin at serine 726. Cells expressing small hairpin RNA for PKAc, dominant-negative PKA Type I?, small interfering RNA for ?-adducin, and ?-adducin with serine 726 mutated to alanine prevented Na,K-ATPase endocytosis. In conclusion, we provide evidence for a new mechanism by which hypercapnia via sAC, cAMP, PKA Type I?, and ?-adducin regulates Na,K-ATPase endocytosis in alveolar epithelial cells.

SUBMITTER: Lecuona E 

PROVIDER: S-EPMC3707378 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Protein kinase A-Iα regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO(2) concentrations.

Lecuona Emilia E   Sun Haiying H   Chen Jiwang J   Trejo Humberto E HE   Baker Margaret A MA   Sznajder Jacob I JI  

American journal of respiratory cell and molecular biology 20130501 5


Elevated concentrations of CO2 (hypercapnia) lead to alveolar epithelial dysfunction by promoting Na,K-ATPase endocytosis. In the present report, we investigated whether the CO2/HCO3(-) activated soluble adenylyl cyclase (sAC) regulates this process. We found that hypercapnia increased the production of cyclic adenosine monophosphate (cAMP) and stimulated protein kinase A (PKA) activity via sAC, which was necessary for Na,K-ATPase endocytosis. During hypercapnia, cAMP was mainly produced in spec  ...[more]

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