A Role for the Circadian Clock Protein Per1 in the Regulation of the NaCl Co-transporter (NCC) and the with-no-lysine Kinase (WNK) Cascade in Mouse Distal Convoluted Tubule Cells

Richards, Jacob; Ko, Benjamin; All, Sean; Cheng, Kit‐Yan; Hoover, Robert S.; Gumz, Michelle L.

doi:10.1074/jbc.m113.531095

Cited by 60 publications

(60 citation statements)

References 53 publications

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“…This night/day difference in pNCC expression was seen in another study as well [59]. Richards et al showed evidence that Per1 facilitates the expression of NCC through the WNK pathway, as reducing the expression of the clock protein resulted in a reduction of NCC, WNK1 and WNK4 as well [60]. Whether or not other core clock genes or clock-controlled genes have an effect on NCC remains to be elucidated.…”

Section: Circadian Rhythms Along the Nephronmentioning

confidence: 63%

Circadian regulation of renal function

Johnston

Pollock

2018

Free Radical Biology and Medicine

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The kidneys regulate many vital functions that require precise control throughout the day. These functions, such as maintaining sodium balance or regulating arterial pressure, rely on an intrinsic clock mechanism that was commonly believed to be controlled by the central nervous system. Mounting evidence in recent years has unveiled previously underappreciated depth of influence by circadian rhythms and clock genes on renal function, at the molecular and physiological level, independent of other external factors. The impact of circadian rhythms in the kidney also affects individuals from a clinical standpoint, as the loss of rhythmic activity or clock gene expression have been documented in various cardiovascular diseases. Fortunately, the prognostic value of examining circadian rhythms may prove useful in determining the progression of a kidney-related disease, and chronotherapy is a clinical intervention that requires consideration of circadian and diurnal rhythms in the kidney. In this review, we discuss evidence of circadian regulation in the kidney from basic and clinical research in order to provide a foundation on which a great deal of future research is needed to expand our understanding of circadian relevant biology.

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Section: Circadian Rhythms Along the Nephronmentioning

confidence: 63%

Circadian regulation of renal function

Johnston

Pollock

2018

Free Radical Biology and Medicine

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“…We began to examine the baseline functional implications of this relationship by measuring amiloride-sensitive uptakes as a measurement of ENaC activity with and without inhibitors of NCC. Here we modified our well-established protocol for measuring NCC function by thiazide-sensitive 22 Na + uptakes in mDCT15 cells (24, 25, 41) to assess amiloride-sensitive 22 Na + uptakes. We simply substituted amiloride into the protocol instead of metolazone.…”

Section: Resultsmentioning

confidence: 99%

The sodium chloride cotransporter (NCC) and epithelial sodium channel (ENaC) associate

Mistry

Wynne

et al. 2016

Biochemical Journal

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The thiazide-sensitive sodium chloride cotransporter (NCC) and the Epithelial Sodium Channel (ENaC) are two of the most important determinants of salt balance and thus systemic blood pressure. Abnormalities in either result in profound changes in blood pressure. There is one segment of the nephron where these two sodium transporters are co-expressed, the second part of the Distal Convoluted Tubule. This is a key part of the aldosterone-sensitive distal nephron, the final regulator of salt handling in the kidney. Aldosterone is the key hormonal regulator for both of these proteins. Despite these shared regulators and co-expression in a key nephron segment, associations between these proteins have not been investigated. After confirming apical localization of these proteins, we demonstrated the presence of functional transport proteins and native association by Blue Native PAGE. Extensive co-immunoprecipitation experiments demonstrated a consistent interaction of NCC with alpha and gamma ENaC. Mammalian two-hybrid studies demonstrated direct binding of NCC to ENaC subunits. Fluorescence Resonance Energy Transfer and immunogold EM studies confirmed that these transport proteins are within appropriate proximity for direct binding. Additionally, we demonstrate that there are functional consequences of this interaction, with inhibition of NCC affecting ENaC function. This novel finding of an association between ENaC and NCC could alter our understanding of salt transport in the distal tubule.

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“…Among patients with essential hypertension, nondippers may become dippers by restricting dietary sodium [32], and the time it takes for nocturnal blood pressure to fall correlates with daytime sodium retention [33]. These effects may be linked to circadian regulation of blood pressure via sodium handling [34][35][36], potentially involving direct regulation of sodium/hydrogen exchanger isoform 3 (NHE3; SLC9A3) [37] and other relevant sodium transporters [38][39][40].…”

Section: Sodium Chronic Kidney Disease and Blood Pressurementioning

confidence: 99%