A role for the circadian clock protein Per1 in the regulation of aldosterone levels and renal Na+ retention
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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 period (Per)1 regulates the expression of multiple Na+ transport genes in the collecting duct, including the α-subunit of the renal epithelial Na+ channel. Consistent with this finding, Per1 knockout mice exhibit dramatically lower blood pressure than wild-type mice. We have also recently demonstrated the potential opposing actions of cryptochrome (Cry)2 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-dehydrogenase isomerase (3β-HSD). Therefore, we tested the hypothesis that Per1 plays a role in the regulation of aldosterone levels and renal Na+ retention. Using RNA silencing and pharmacological blockade of Per1 nuclear entry in the NCI-H295R human adrenal cell line, we showed that Per1 regulates 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 would have a renal Na+-retaining defect. Indeed, metabolic cage experiments demonstrated that Per1 heterozygotes excreted more urinary Na+ compared with wild-type mice. Taken together, these data support the hypothesis that Per1 regulates aldosterone levels and that Per1 plays an integral role in the regulation of Na+ retention.
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PER1 plays an important role in blood pressure maintenance by regulating aldosterone levels and affecting sodium retention.
“PER1 plays an important role in BP maintenance by regulating aldosterone levels and affecting sodium retention (71)(72)(73).”
From Role of the circadian system in cardiovascular disease (2018) · cites this paper as [71]
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Self-citationThe Circadian Clock in the Mammalian Kidney
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Additional file 1 of Reversible dysregulation of renal circadian rhythm in lupus nephritis
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- Authors
- Richards, J., Cheng, K.-Y., All, S., Skopis, G., Jeffers, L., Jeanette Lynch, I., Wingo, C. S., & Gumz, M. L.
- Affiliations
- University of Florida (US)
- Department of Medicine, University of Florida, Gainsville, Florida;
- Corresponding author
- Gumz, Michelle L.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2013-12-15
- Volume
- 305
- Issue
- 12
- Pages
- F1697-F1704
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC3882450
- OpenAlex
- W2100229060
- Cited by
- 63
- References
- 41
- Citations by year
- 2024: 1 · 2023: 4 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 4
- FWCI
- 2.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007518, DK-085193, R03DK098460, L30 DK096643, K01DK085193, DK-098460)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- Per1, circadian clock, aldosterone, 3β-hydroxysteroid dehydrogenase, cryptochrome, adrenal gland, blood pressure, sodium excretion, collecting duct, epithelial Na+ channel
- MeSH terms
- Adrenal Glands, Aldosterone, Animals, Cell Line, Cells, Cultured, Humans, Kidney, Male, Sodium, 3-Hydroxysteroid Dehydrogenases, Mice, Knockout, Models, Animal, RNA, Small Interfering, Mice, Cryptochromes, Period Circadian Proteins, In Vitro Techniques
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