High dietary potassium causes ubiquitin-dependent degradation of the kidney sodium-chloride cotransporter.

ABSTRACT: The thiazide-sensitive sodium-chloride cotransporter (NCC) in the renal distal convoluted tubule (DCT) plays a critical role in regulating blood pressure (BP) and K⁺ homeostasis. During hyperkalemia, reduced NCC phosphorylation and total NCC abundance facilitate downstream electrogenic K⁺ secretion and BP reduction. However, the mechanism for the K⁺-dependent reduction in total NCC levels is unknown. Here, we show that NCC levels were reduced in ex vivo renal tubules incubated in a high-K⁺ medium for 24-48 h. This reduction was independent of NCC transcription, but was prevented using inhibitors of the proteasome (MG132) or lysosome (chloroquine). Ex vivo, high K⁺ increased NCC ubiquitylation, but inhibition of the ubiquitin conjugatio

SUBMITTER: Kortenoeven MLA 

PROVIDER: S-EPMC8318901 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature