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- W2996340013 abstract "Dietary K+ load results in hyperkalemia, with consequent aldosterone release in order to stimulate K+ secretion in the distal nephron. The molecular mechanisms of this regulation are still not fully elucidated. Here, we aim to identify the role of the aldosterone induced SGK1 kinase and its target, the ubiquitin-protein ligase NEDD4-2 in the regulation of short and long term K+ secretion. To avoid the compensatory mechanisms which may mask the role of SGK1 and Nedd4-2 during kidney development, we employed the previously described inducible nephron specific SGK1-KO and Nedd4-2-KO mouse models in which a deletion of the target gene in renal tubules was observed. Our results indicate that short-term K+ regulation (30 min to 2h) is not altered in SGK1 KO mice. However, these animals exhibit 35% decrease in urinary K+ excretion after 2 days of exposure to high K+ diet (5%) leading to hyperkalemia. Molecular analysis of WT and SGK1 KO mice after 2 days of HK diet revealed that the cleavage and the membrane localization of ENaC alpha and gamma subunits are decreased in the KO mice. On the same line, Nedd4-2 phosphorylation was also decreased suggesting that NEDD4-2 mediated internalization of ENaC is more active in mutant mice. Interestingly, when Nedd4-2 KO mice were challenged by low K+ diet (<0.1%), they showed an abnormal ability to handle K+ deprivation. More specifically, they exhibit hypokalemia and urinary K+ loss likely mediated by increased ENaC activity as demonstrated by the increased membrane localization of alpha and gamma ENaC subunits. In conclusion, our data suggest that SGK1 and its target NEDD4-2 control K+ homeostasis through the regulation of ENaC membrane localization" @default.
- W2996340013 created "2019-12-26" @default.
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- W2996340013 date "2015-04-01" @default.
- W2996340013 modified "2023-09-23" @default.
- W2996340013 title "The SGK1/NEDD4‐2 pathway is crucial in regulating renal potassium secretion" @default.
- W2996340013 doi "https://doi.org/10.1096/fasebj.29.1_supplement.666.5" @default.
- W2996340013 hasPublicationYear "2015" @default.
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