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Protein Carbonylation of an Amino Acid Residue of the Na/K‐ATPase α1 Subunit Determines Na/K‐ATPase Signaling and Sodium Transport in Renal Proximal Tubular Cells
- Source :
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 5, Iss 9, Pp n/a-n/a (2016), Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
Abstract
- Background We have demonstrated that cardiotonic steroids, such as ouabain, signaling through the Na/K‐ ATP ase, regulate sodium reabsorption in the renal proximal tubule. By direct carbonylation modification of the Pro222 residue in the actuator (A) domain of pig Na/K‐ ATP ase α1 subunit, reactive oxygen species are required for ouabain‐stimulated Na/K‐ ATP ase/c‐Src signaling and subsequent regulation of active transepithelial 22 Na + transport. In the present study we sought to determine the functional role of Pro222 carbonylation in Na/K‐ ATP ase signaling and sodium handling. Methods and Results Stable pig α1 knockdown LLC ‐ PK 1‐originated PY ‐17 cells were rescued by expressing wild‐type rat α1 and rat α1 with a single mutation of Pro224 (corresponding to pig Pro222) to Ala. This mutation does not affect ouabain‐induced inhibition of Na/K‐ ATP ase activity, but abolishes the effects of ouabain on Na/K‐ ATP ase/c‐Src signaling, protein carbonylation, Na/K‐ ATP ase endocytosis, and active transepithelial 22 Na + transport. Conclusions Direct carbonylation modification of Pro224 in the rat α1 subunit determines ouabain‐mediated Na/K‐ ATP ase signal transduction and subsequent regulation of renal proximal tubule sodium transport.
- Subjects :
- 0301 basic medicine
lcsh:Diseases of the circulatory (Cardiovascular) system
Swine
Sodium-Potassium-Exchanging ATPase
ATPase
030204 cardiovascular system & hematology
Ouabain
Animals, Genetically Modified
CSK Tyrosine-Protein Kinase
Kidney Tubules, Proximal
0302 clinical medicine
Medicine
Cells, Cultured
Original Research
reactive oxygen species
biology
sodium transport
src-Family Kinases
Na/K‐ATPase
Gene Knockdown Techniques
Hypertension
protein trafficking
Signal transduction
Cardiology and Cardiovascular Medicine
signaling
Signal Transduction
medicine.drug
medicine.medical_specialty
Protein Carbonylation
Sodium
chemistry.chemical_element
protein carbonylation
03 medical and health sciences
Internal medicine
Animals
Na+/K+-ATPase
Renal sodium reabsorption
business.industry
Ion Channels/Membrane Transport
Molecular biology
Rats
030104 developmental biology
Endocrinology
chemistry
13. Climate action
lcsh:RC666-701
Mutation
biology.protein
Oxidant Stress
business
Cell Signalling/Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20479980
- Volume :
- 5
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
- Accession number :
- edsair.doi.dedup.....7138c504dd900417e5f3f6f0448de318