Dec1 and CLOCK Regulate Na+ /K+ -ATPase β1 Subunit Expression and Blood Pressure

Hypertension
Ayumu NakashimaYukio Kato

Abstract

Blood pressure shows a circadian rhythm, and recent studies have suggested the involvement of a molecular clock system in its control. In the clock system, the CLOCK (circadian locomotor output cycles kaput):BMAL1 (brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1) heterodimer enhances promoter activity of clock genes, and DEC1 (BHLHE40/STRA13/SHARP-2) represses CLOCK/BMAL1-enhanced promoter activity through competition for binding to the clock element, CACGTG E-box. However, the molecular mechanisms by which this system regulates blood pressure remain unclear. Here, we show that DEC1 suppressed the expression of ATP1B1, which encodes the β1 subunit of the Na+/K+-ATPase and elevated blood pressure. Using chromatin immunoprecipitation and chromatin immunoprecipitation-on-chip analyses, we found that DEC1 and CLOCK bound to E-boxes in the ATP1B1 promoter. Luciferase assays revealed that CLOCK:BMAL1 heterodimer enhanced transcription from the ATP1B1 promoter, whereas DEC1 suppressed this transactivation. Accordingly, Atp1b1 mRNA and protein levels in mouse kidney, aorta, and heart showed a circadian rhythm that was antiphasic to the blood pressure rhythm. Furthermore, Dec1-deficient mice showed enhance...Continue Reading

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Citations

Aug 29, 2019·Proceedings of the National Academy of Sciences of the United States of America·Kathryn G PowersRichard E Mains
Oct 11, 2019·International Journal of Molecular Sciences·Hue Thi LeMasanori Nakata
Oct 23, 2019·Annual Review of Physiology·Dingguo Zhang, David M Pollock
Feb 5, 2019·Internal Medicine·Yasuyuki NagasawaMasaharu Ishihara
Mar 4, 2020·Toxins·Sol CarriazoAlberto Ortiz
Nov 21, 2020·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Amin HaghaniCaleb E Finch
Jan 29, 2021·The Journal of Clinical Endocrinology and Metabolism·Yanjiao WangJianzhong Yin
Jan 9, 2021·Function·Dingguo ZhangDavid M Pollock
Aug 4, 2021·Progress in Neurobiology·Telma QuintelaCecília R A Santos

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