Document Detail


Protein kinase A-Iα regulates Na,K-ATPase endocytosis in alveolar epithelial cells exposed to high CO(2) concentrations.
MedLine Citation:
PMID:  23349050     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Iα activation. In alveolar epithelial cells exposed to high CO2 concentrations, PKA Type Iα regulated the time-dependent phosphorylation of the actin cytoskeleton component α-adducin at serine 726. Cells expressing small hairpin RNA for PKAc, dominant-negative PKA Type Iα, small interfering RNA for α-adducin, and α-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 Iα, and α-adducin regulates Na,K-ATPase endocytosis in alveolar epithelial cells.
Authors:
Emilia Lecuona; Haiying Sun; Jiwang Chen; Humberto E Trejo; Margaret A Baker; Jacob I Sznajder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-06-25     Revised Date:  2013-10-23    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  626-34     Citation Subset:  IM    
Affiliation:
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. e-lecuona@northwestern.edu
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Animals
Calmodulin-Binding Proteins / metabolism
Carbon Dioxide / pharmacology*
Cell Line, Tumor
Cell Membrane / enzymology
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / physiology*
Endocytosis*
Humans
Hypercapnia / enzymology
Phosphorylation
Pneumocytes / drug effects,  enzymology*,  physiology
Protein Kinase C / metabolism
Protein Processing, Post-Translational
Rats
Rats, Sprague-Dawley
Second Messenger Systems
Sodium-Potassium-Exchanging ATPase / metabolism*
Grant Support
ID/Acronym/Agency:
HL85534/HL/NHLBI NIH HHS; R01 HL085534/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Calmodulin-Binding Proteins; 0/Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0/PRKAR1A protein, human; 0/adducin; 124-38-9/Carbon Dioxide; 60-92-4/Cyclic AMP; EC 2.7.11.13/Protein Kinase C; EC 3.6.1.-/ATP1A1 protein, human; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase; EC 4.6.1.1/Adenylate Cyclase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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