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10.1038/srep18311

http://scihub22266oqcxt.onion/10.1038/srep18311
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suck abstract from ncbi


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pmid26674602
      Sci+Rep 2015 ; 5 (ä): 18311
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  • Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus #MMPMID26674602
  • Khositseth S ; Uawithya P ; Somparn P ; Charngkaew K ; Thippamom N ; Hoffert JD ; Saeed F ; Michael Payne D ; Chen SH ; Fenton RA ; Pisitkun T
  • Sci Rep 2015[Dec]; 5 (ä): 18311 PMID26674602 show ga
  • 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. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.
  • |*Autophagy [MESH]
  • |Actin Cytoskeleton/metabolism [MESH]
  • |Animals [MESH]
  • |Aquaporin 2/*metabolism [MESH]
  • |Chromatography, Liquid [MESH]
  • |Diabetes Insipidus, Nephrogenic/*metabolism/physiopathology [MESH]
  • |Hypokalemia/*metabolism/physiopathology [MESH]
  • |Immunoblotting [MESH]
  • |Kidney Medulla/metabolism [MESH]
  • |Kidney Tubules, Collecting/metabolism/ultrastructure [MESH]
  • |Lysosomal Membrane Proteins/metabolism [MESH]
  • |Male [MESH]
  • |Microscopy, Immunoelectron [MESH]
  • |Microtubule-Associated Proteins/metabolism [MESH]
  • |Phagosomes/metabolism/ultrastructure [MESH]
  • |Proteome/metabolism [MESH]
  • |Proteomics/methods [MESH]
  • |Rats, Sprague-Dawley [MESH]
  • |Tandem Mass Spectrometry [MESH]


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