Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus
Khositseth,
Sookkasem; Uawithya,
Panapat; Somparn,
Poorichaya; Charngkaew,
Komgrid; Thippamom,
Nattakan; Hoffert,
Jason D; Saeed,
Fahad; Michael Payne,
D; Chen,
Shu-Hui; Fenton,
Robert A; ,
Nature Publishing Group UK London Scientific reports
5
:18311
(2015).
Abstract
Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins …