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  Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway

Ehret, E., Jaeger, Y., Sergi, C., Merillat, A.-M., Peyrollaz, T., Anand, D., et al. (2022). Kidney-Specific CAP1/Prss8-Deficient Mice Maintain ENaC-Mediated Sodium Balance through an Aldosterone Independent Pathway. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 23(12): 6745. doi:10.3390/ijms23126745.

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 Creators:
Ehret, Elodie, Author
Jaeger, Yannick1, Author           
Sergi, Chloe, Author
Merillat, Anne-Marie, Author
Peyrollaz, Thibaud, Author
Anand, Deepika, Author
Wang, Qing, Author
Ino, Frederique, Author
Maillard, Marc, Author
Kellenberger, Stephan, Author
Gautschi, Ivan, Author
Szabo, Roman, Author
Bugge, Thomas H., Author
Vogel, Lotte K., Author
Hummler, Edith, Author
Frateschi, Simona, Author
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

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 Abstract: The serine protease prostasin (CAP1/Prss8, channel-activating protease-1) is a confirmed in vitro and in vivo activator of the epithelial sodium channel ENaC. To test whether proteolytic activity or CAP1/Prss8 abundance itself are required for ENaC activation in the kidney, we studied animals either hetero- or homozygous mutant at serine 238 (S238A; Prss8(cat/+) and Prss8(cat/cat)), and renal tubule-specific CAP1/Prss8 knockout (Prss8(PaxLC1)) mice. When exposed to varying Na+-containing diets, no changes in Na+ and K+ handling and only minor changes in the expression of Na+ and K+ transporting protein were found in both models. Similarly, the alpha- or gamma ENaC subunit cleavage pattern did not differ from control mice. On standard and low Na+ diet, Prss8(cat/+) and Prss8(cat/cat) mice exhibited standard plasma aldosterone levels and unchanged amiloride-sensitive rectal potential difference indicating adapted ENaC activity. Upon Na+ deprivation, mice lacking the renal CAP1/Prss8 expression (Prss8(PaxLC1)) exhibit significantly decreased plasma aldosterone and lower K+ levels but compensate by showing significantly higher plasma renin activity. Our data clearly demonstrated that the catalytic activity of CAP1/Prss8 is dispensable for proteolytic ENaC activation. CAP1/Prss8-deficiency uncoupled ENaC activation from its aldosterone dependence, but Na+ homeostasis is maintained through alternative pathways.

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 Dates: 2022-06-16
 Publication Status: Published online
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 Rev. Type: -
 Identifiers: ISI: 000818268700001
DOI: 10.3390/ijms23126745
PMID: 35743186
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Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Source Genre: Journal
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Pages: - Volume / Issue: 23 (12) Sequence Number: 6745 Start / End Page: - Identifier: -