A Role for the Circadian Clock Protein Per1 in the Regulation of Aldosterone Levels and Renal Sodium Retention.

A Role for the Circadian Clock Protein Per1 in the Regulation of Aldosterone Levels and Renal Sodium Retention. Am J Physiol Renal Physiol. 2013 Oct 23; Authors: Richards J, Cheng KY, All SC, Skopis G, Jeffers LA, Lynch IJ, Wingo CS, Gumz ML Abstract The circadian clock plays an important role in the regulation of physiological processes including renal function and blood pressure. We have previously shown that the circadian protein Per1 positively regulates expression of multiple sodium transport genes in the collecting duct including the alpha subunit of the renal epithelial sodium channel (αENaC). Consistent with this finding, Per1 KO mice exhibit dramatically lower BP than WT mice. We have also recently demonstrated the potential opposing actions of Cry2 on Per1 target genes. Recent work by others has demonstrated that Cry1/2 regulates aldosterone production through increased expression of the adrenal gland-specific rate-limiting enzyme, 3β-HSD. Therefore, we tested the hypothesis that Per1 plays a role in the regulation of aldosterone levels and renal sodium retention. Using RNA silencing and pharmacological blockade of Per1 nuclear entry in the NCI-H295R human adrenal cell line, we showed that Per1 regulated 3β-HSD expression in vitro. These results were confirmed in vivo: mice with reduced levels of Per1 had decreased levels of plasma aldosterone and decreased mRNA expression of 3β-HSD. We postulated that mice with reduced Per1 woul...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research