Artikel ; Online: Changes in V-ATPase subunits of human urinary exosomes reflect the renal response to acute acid/alkali loading and the defects in distal renal tubular acidosis.
2018 Band 93, Heft 4, Seite(n) 871–880
Abstract: In the kidney, final urinary acidification is achieved by V-ATPases expressed in type A intercalated cells. The B1 subunit of the V-ATPase is required for maximal urinary acidification, while the role of the homologous B2 subunit is less clear. Here we ... ...
| Abstract | In the kidney, final urinary acidification is achieved by V-ATPases expressed in type A intercalated cells. The B1 subunit of the V-ATPase is required for maximal urinary acidification, while the role of the homologous B2 subunit is less clear. Here we examined the effect of acute acid/alkali loading in humans on B1 and B2 subunit abundance in urinary exosomes in normal individuals and of acid loading in patients with distal renal tubular acidosis (dRTA). Specificities of B1 and B2 subunit antibodies were verified by yeast heterologously expressing human B1 and B2 subunits, and murine wild-type and B1-deleted kidney lysates. Acute ammonium chloride loading elicited systemic acidemia, a drop in urinary pH, and increased urinary ammonium excretion. Nadir urinary pH was achieved at four to five hours, and exosomal B1 abundance was significantly increased at two through six hours after ammonium chloride loading. After acute equimolar sodium bicarbonate loading, blood and urinary pH rose rapidly, with a concomitant reduction of exosomal B1 abundance within two hours, which remained lower throughout the test. In contrast, no change in exosomal B2 abundance was found following acid or alkali loading. In patients with inherited or acquired distal RTA, the urinary B1 subunit was extremely low or undetectable and did not respond to acid loading in urine, whereas no change in B2 subunit was found. Thus, both B1 and B2 subunits of the V-ATPase are detectable in human urinary exosomes, and acid and alkali loading or distal RTA cause changes in the B1 but not B2 subunit abundance in urinary exosomes. |
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| Mesh-Begriff(e) | Acidosis, Renal Tubular/enzymology ; Acidosis, Renal Tubular/genetics ; Acidosis, Renal Tubular/physiopathology ; Acidosis, Renal Tubular/urine ; Adult ; Ammonium Chloride/administration & dosage ; Animals ; Bicarbonates/administration & dosage ; Exosomes/drug effects ; Exosomes/enzymology ; Humans ; Hydrogen-Ion Concentration ; Kidney Tubules/drug effects ; Kidney Tubules/enzymology ; Kidney Tubules/physiopathology ; Male ; Mice, Knockout ; Middle Aged ; Mutation ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae/genetics ; Vacuolar Proton-Translocating ATPases/genetics ; Vacuolar Proton-Translocating ATPases/metabolism ; Vacuolar Proton-Translocating ATPases/urine ; Water-Electrolyte Balance/drug effects ; Young Adult | |||||
| Chemische Substanzen | ATP6V1B1 protein, human ; Bicarbonates ; Ammonium Chloride (01Q9PC255D) ; ammonium bicarbonate (45JP4345C9) ; Atp6v1b1 protein, mouse (EC 3.6.1.-) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; ATP6V1B2 protein, human (EC 7.1.2.2) | |||||
| Sprache | Englisch | |||||
| Erscheinungsdatum | 2018-01-06 | |||||
| Erscheinungsland | United States | |||||
| Dokumenttyp | Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 120573-0 | |||||
| ISSN | 1523-1755 ; 0085-2538 | |||||
| ISSN (online) | 1523-1755 | |||||
| ISSN | 0085-2538 | |||||
| DOI | 10.1016/j.kint.2017.10.018 | |||||
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| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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