Proteolytic processing of epithelial sodium channels by prostasin in human kidneys

Abstract only ENaC activity is regulated by proteolysis of γENaC. Prostasin is believed to be a relevant protease‐candidate and aldosterone is thought to up‐regulate prostasin and the cleavage of γENaC. There is no information on the proteolytic processing of ENaC in human kidney. The aim was to inv...

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Bibliographic Details
Published in:The FASEB journal Vol. 27; no. S1
Main Authors: Zachar, Rikke Meldgaard, Svenningsen, Per, Marcussen, Niels, Walter, Steen, Skjoedt, Karsten, Jensen, Boye L
Format: Journal Article
Language:English
Published: 01-04-2013
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Summary:Abstract only ENaC activity is regulated by proteolysis of γENaC. Prostasin is believed to be a relevant protease‐candidate and aldosterone is thought to up‐regulate prostasin and the cleavage of γENaC. There is no information on the proteolytic processing of ENaC in human kidney. The aim was to investigate the proteolytic processing of γENaC in human kidney and examine the role of aldosterone on the processing. Monoclonal antibodies (mAb) that distinguish between cleaved and non‐cleaved γENaC were developed. Immunohistochemistry, western blotting and ELISA were utilized to test the hypothesis on human kidney tissue obtained from nephrectomy specimens after informed consent. Immunoblotting with mAb directed against the inhibitory domain reveals three bands in a human kidney cortex pool corresponding to full length, furin‐ and prostasin cleavage products. The effect of aldosterone on γENaC was tested using kidney tissue obtained from patients recieving no medication, patients given diuretics and patients receiving ACE inhibitors. The abundance of full length γENaC was elevated in patients receiving diuretics but there was no consistent change in prostasin‐cleavage product. The results indicate that proteolytic processing of γENaC occurs in human kidney and aldosterone enhances γENaC abundance.
ISSN:0892-6638
1530-6860
DOI:10.1096/fasebj.27.1_supplement.912.18