Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Am J Physiol Renal Physiol
2019 May 01;3165:F807-F813. doi: 10.1152/ajprenal.00408.2018.
Show Gene links
Show Anatomy links
Direct and indirect inhibition of the circadian clock protein Per1: effects on ENaC and blood pressure.
Alli A
,
Yu L
,
Holzworth M
,
Richards J
,
Cheng KY
,
Lynch IJ
,
Wingo CS
,
Gumz ML
.
???displayArticle.abstract???
Circadian rhythms govern physiological functions and are important for overall health. The molecular circadian clock comprises several transcription factors that mediate circadian control of physiological function, in part, by regulating gene expression in a tissue-specific manner. These connections are well established, but the underlying mechanisms are incompletely understood. The overall goal of this study was to examine the connection among the circadian clock protein Period 1 (Per1), epithelial Na+ channel (ENaC), and blood pressure (BP) using a multipronged approach. Using global Per1 knockout mice on a 129/sv background in combination with a high-salt diet plus mineralocorticoid treatment, we demonstrated that loss of Per1 in this setting is associated with protection from hypertension. Next, we used the ENaC inhibitor benzamil to demonstrate a role for ENaC in BP regulation and urinary Na+ excretion in 129/sv mice. We targeted Per1 indirectly using pharmacological inhibition of Per1 nuclear entry in vivo to demonstrate altered expression of known Per1 target genes as well as a BP-lowering effect in 129/sv mice. Finally, we directly inhibited Per1 via genetic knockdown in amphibian distalnephron cells to demonstrate, for the first time, that reduced Per1 expression is associated with decreased ENaC activity at the single channel level.
Alli,
Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein.
2012, Pubmed,
Xenbase
Alli,
Phosphatidylinositol phosphate-dependent regulation of Xenopus ENaC by MARCKS protein.
2012,
Pubmed
,
Xenbase
Alli,
Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane.
2015,
Pubmed
,
Xenbase
Berman,
Physiological regulation of the epithelial Na+ channel by casein kinase II.
2018,
Pubmed
Chang,
Loss of GSTM1, a NRF2 target, is associated with accelerated progression of hypertensive kidney disease in the African American Study of Kidney Disease (AASK).
2013,
Pubmed
Douma,
Circadian clock-mediated regulation of blood pressure.
2018,
Pubmed
Douma,
Female C57BL/6J mice lacking the circadian clock protein PER1 are protected from nondipping hypertension.
2019,
Pubmed
Durukan,
Low plasma renin activity and high aldosterone/renin ratio are associated with untreated isolated systolic hypertension.
2012,
Pubmed
Gumz,
The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice.
2009,
Pubmed
Gurley,
Influence of genetic background on albuminuria and kidney injury in Ins2(+/C96Y) (Akita) mice.
2010,
Pubmed
Hartner,
Strain differences in the development of hypertension and glomerular lesions induced by deoxycorticosterone acetate salt in mice.
2003,
Pubmed
Jella,
Exosomal GAPDH from Proximal Tubule Cells Regulate ENaC Activity.
2016,
Pubmed
,
Xenbase
Kleyman,
Epithelial Na+ Channel Regulation by Extracellular and Intracellular Factors.
2018,
Pubmed
Liu,
Associations of epithelial sodium channel genes with blood pressure: the GenSalt study.
2015,
Pubmed
Lynch,
Effect of mineralocorticoid treatment in mice with collecting duct-specific knockout of endothelin-1.
2015,
Pubmed
Meneton,
High plasma aldosterone and low renin predict blood pressure increase and hypertension in middle-aged Caucasian populations.
2008,
Pubmed
Montgomery,
ENaC activity is regulated by calpain-2 proteolysis of MARCKS proteins.
2017,
Pubmed
,
Xenbase
Petkov,
An efficient SNP system for mouse genome scanning and elucidating strain relationships.
2004,
Pubmed
Ray,
Human epithelial Na+ channel missense variants identified in the GenSalt study alter channel activity.
2016,
Pubmed
,
Xenbase
Reifenberger,
Cytochalasin E alters the cytoskeleton and decreases ENaC activity in Xenopus 2F3 cells.
2014,
Pubmed
,
Xenbase
Richards,
A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention.
2013,
Pubmed
Richards,
Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε.
2012,
Pubmed
Richards,
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.
2014,
Pubmed
Richards,
Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney.
2013,
Pubmed
Richards,
Role of Per1 and the mineralocorticoid receptor in the coordinate regulation of αENaC in renal cortical collecting duct cells.
2013,
Pubmed
Solocinski,
Transcriptional regulation of NHE3 and SGLT1 by the circadian clock protein Per1 in proximal tubule cells.
2015,
Pubmed
Solocinski,
Desoxycorticosterone pivalate-salt treatment leads to non-dipping hypertension in Per1 knockout mice.
2017,
Pubmed
Stow,
The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes.
2012,
Pubmed
Thosar,
Role of the circadian system in cardiovascular disease.
2018,
Pubmed
Tiwari,
Trafficking of ENaC subunits in response to acute insulin in mouse kidney.
2007,
Pubmed
Van Laake,
The circadian clock in cardiovascular regulation and disease: Lessons from the Nobel Prize in Physiology or Medicine 2017.
2018,
Pubmed
Wang,
Filamin interacts with epithelial sodium channel and inhibits its channel function.
2013,
Pubmed
,
Xenbase
Zhang,
A circadian gene expression atlas in mammals: implications for biology and medicine.
2014,
Pubmed
Zhang,
Attenuation of lithium-induced natriuresis and kaliuresis in P2Y₂ receptor knockout mice.
2013,
Pubmed