Document Detail


Involvement of reactive oxygen species in a feed-forward mechanism of Na/K-ATPase-mediated signaling transduction.
MedLine Citation:
PMID:  24121502     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiotonic steroids (such as ouabain) signaling through Na/K-ATPase regulate sodium reabsorption in the renal proximal tubule. We report here that reactive oxygen species are required to initiate ouabain-stimulated Na/K-ATPase·c-Src signaling. Pretreatment with the antioxidant N-acetyl-L-cysteine prevented ouabain-stimulated Na/K-ATPase·c-Src signaling, protein carbonylation, redistribution of Na/K-ATPase and sodium/proton exchanger isoform 3, and inhibition of active transepithelial (22)Na(+) transport. Disruption of the Na/K-ATPase·c-Src signaling complex attenuated ouabain-stimulated protein carbonylation. Ouabain-stimulated protein carbonylation is reversed after removal of ouabain, and this reversibility is largely independent of de novo protein synthesis and degradation by either the lysosome or the proteasome pathways. Furthermore, ouabain stimulated direct carbonylation of two amino acid residues in the actuator domain of the Na/K-ATPase α1 subunit. Taken together, the data indicate that carbonylation modification of the Na/K-ATPase α1 subunit is involved in a feed-forward mechanism of regulation of ouabain-mediated renal proximal tubule Na/K-ATPase signal transduction and subsequent sodium transport.
Authors:
Yanling Yan; Anna P Shapiro; Steven Haller; Vinai Katragadda; Lijun Liu; Jiang Tian; Venkatesha Basrur; Deepak Malhotra; Zi-jian Xie; Nader G Abraham; Joseph I Shapiro; Jiang Liu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-10-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-25     Completed Date:  2014-02-04     Revised Date:  2014-10-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34249-58     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Animals
Cell Line
Enzyme Inhibitors / pharmacology
Free Radical Scavengers / pharmacokinetics
Multienzyme Complexes / genetics,  metabolism*
Ouabain / pharmacology
Protein Carbonylation / drug effects,  genetics
Proteolysis / drug effects
Reactive Oxygen Species / metabolism*
Signal Transduction / drug effects,  physiology*
Sodium-Potassium-Exchanging ATPase / genetics,  metabolism*
Swine
src-Family Kinases
Grant Support
ID/Acronym/Agency:
R01 HL-105649/HL/NHLBI NIH HHS; R01 HL-109015/HL/NHLBI NIH HHS; R01 HL105649/HL/NHLBI NIH HHS; R01 HL109015/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Free Radical Scavengers; 0/Multienzyme Complexes; 0/Reactive Oxygen Species; 5ACL011P69/Ouabain; EC 2.7.10.2/CSK tyrosine-protein kinase; EC 2.7.10.2/src-Family Kinases; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase; WYQ7N0BPYC/Acetylcysteine

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


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