Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone
| Autor: | Toichiro Takizawa, Akihito Ohta, Tatemitsu Rai, Shinichi Uchida, Sei Sasaki, Motoko Chiga, Sung-Sen Yang |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
hypertension medicine.drug_class Pseudohypoaldosteronism Sodium Chloride Symporter Inhibitors NaCl reabsorption Protein Serine-Threonine Kinases Biology Article Mice chemistry.chemical_compound pseudohypoaldosteronism type II Internal medicine knock-in mouse medicine Animals Phosphorylation Sodium Chloride Dietary Aldosterone urogenital system Kinase Apical membrane WNK1 medicine.disease Sodium Chloride Symporters WNK4 Disease Models Animal Endocrinology chemistry Nephrology Mineralocorticoid Protein Kinases |
| Zdroj: | Kidney International. 74:1403-1409 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2008.451 |
| Popis: | Pseudohypoaldosteronism type II (PHAII) is caused by mutations in the WNK1 and WNK4 genes (WNK with-no-lysine kinase). In a mouse model of this disease where a mutant of Wnk4 D561A was knocked in, increased phosphorylation of the sodium chloride cotransporter (NCC) was found and the transporter was concentrated on the apical membrane of the distal tubules. In addition, we recently found that other kinases, such as the oxidative stress response kinase-1/STE20/SPS1-related proline alanine–rich kinase (OSR1/SPAK), also showed increased phosphorylation in these mice. Here we determined whether this kinase cascade is regulated by dietary salt intake. We found that the phosphorylation states of NCC and OSR1/SPAK were increased by low-salt diets and decreased by high-salt diets; a regulation completely lost in the knock-in mice. Increased phosphorylation was reversed by spironolactone and this decreased phosphorylation was reversed by administration of exogenous aldosterone. These studies suggest that that the WNK-OSR1/SPAK-NCC cascade may be a novel effector system of aldosterone action in the kidney. |
| Databáze: | OpenAIRE |
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