Document Detail


Role of the small GTPase RhoA in the hypoxia-induced decrease of plasma membrane Na,K-ATPase in A549 cells.
MedLine Citation:
PMID:  17550967     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxia impairs alveolar fluid reabsorption by promoting Na,K-ATPase endocytosis, from the plasma membrane of alveolar epithelial cells. The present study was designed to determine whether hypoxia induces Na,K-ATPase endocytosis via reactive oxygen species (ROS)-mediated RhoA activation. In A549 cells, RhoA activation occurred within 15 minutes of cells exposure to hypoxia. This activation was inhibited in cells infected with adenovirus coding for gluthatione peroxidase (an H2O2 scavenger), in mitochondria depleted (rho0) cells or cells expressing decreased levels of the Rieske iron-sulfur protein (inhibitor of mitochondrial complex III), which suggests a role for mitochondrial ROS. Moreover, exogenous H2O2 treatment during normoxia mimicked the effects of hypoxia on RhoA, further supporting a role for ROS. Cells expressing dominant negative RhoA failed to endocytose the Na,K-ATPase during hypoxia or after H2O2 treatment. Na,K-ATPase endocytosis was also prevented in cells treated with Y-27632, a Rho-associated kinase (ROCK) inhibitor, and in cells expressing dominant negative ROCK. In summary, we provide evidence that in human alveolar epithelial cells exposed to hypoxia, RhoA/ROCK activation is necessary for Na,K-ATPase endocytosis via a mechanism that requires mitochondrial ROS.
Authors:
Laura A Dada; Eva Novoa; Emilia Lecuona; Haiying Sun; Jacob I Sznajder
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-06-05
Journal Detail:
Title:  Journal of cell science     Volume:  120     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-26     Completed Date:  2007-11-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2214-22     Citation Subset:  IM    
Affiliation:
Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. lauradada@northwestern.edu
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Amides / pharmacology
Bronchoalveolar Lavage Fluid
Cell Hypoxia
Cell Line
Cell Membrane / enzymology*,  genetics
Electron Transport Complex III / metabolism
Endocytosis* / drug effects,  genetics
Enzyme Activation* / drug effects,  genetics
Enzyme Inhibitors / pharmacology
Free Radical Scavengers / metabolism
Genes, Dominant
Glutathione Peroxidase / genetics,  metabolism
Humans
Hydrogen Peroxide / metabolism
Iron-Sulfur Proteins / metabolism
Mitochondria / genetics,  metabolism
Pyridines / pharmacology
Respiratory Mucosa / enzymology*
Sodium-Potassium-Exchanging ATPase / genetics,  metabolism*
Transduction, Genetic
rhoA GTP-Binding Protein / antagonists & inhibitors,  metabolism*
Grant Support
ID/Acronym/Agency:
HL-P01-71643/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Amides; 0/Enzyme Inhibitors; 0/Free Radical Scavengers; 0/Iron-Sulfur Proteins; 0/Pyridines; 0/Rieske iron-sulfur protein; 138381-45-0/Y 27632; 7722-84-1/Hydrogen Peroxide; EC 1.10.2.2/Electron Transport Complex III; EC 1.11.1.9/Glutathione Peroxidase; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase; EC 3.6.5.2/rhoA GTP-Binding Protein

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


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