Mechanism of the circadian clock in physiology

Richards, Jacob; Gumz, Michelle L.

doi:10.1152/ajpregu.00066.2013

Cited by 117 publications

(93 citation statements)

References 156 publications

(156 reference statements)

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“…Now it is well established that circadian rhythms exist in almost all life forms, from simple archaebacteria to complex humans [2]. In mammals, mounting evidence has demonstrated that the circadian clock regulates a multitude of physiological functions including but not limited to: metabolism, immune response, renal function, sleep-wake cycles, and blood pressure [3, 4]. Interestingly, it has been shown that deregulation of the circadian clock can also be attributed to certain pathological states, including hypertension [5].…”

Section: Introductionmentioning

confidence: 99%

Clock genes in hypertension

Richards

Diaz²,

Gumz

2014

Blood Pressure Monitoring

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The circadian clock plays an integral role in the regulation of physiological processes, including the regulation of blood pressure. However, deregulation of the clock can lead to pathophysiological states including hypertension. Recent work has implicated the circadian clock genes in the regulation of processes in the heart, kidney, vasculature, and the metabolic organs, which are all critical in the regulation of the blood pressure. The goal of this review is to provide an introduction and general overview into the role of circadian clock genes in the regulation of blood pressure with a focus on their deregulation in the etiology of hypertension. This review will focus on the core circadian clock genes CLOCK, BMAL1, Per, and Cry.

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Section: Introductionmentioning

confidence: 99%

Clock genes in hypertension

Richards

Diaz²,

Gumz

2014

Blood Pressure Monitoring

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“…THE CIRCADIAN CLOCK IS AN important regulator of many physiological functions including blood pressure; metabolism; and endocrine, immune, vascular, and renal function (1,6,30,40,43,44,49). The canonical circadian clock molecular mechanism, known as the transcription translational oscillating (TTO) loop, involves four core proteins that interact with each other to regulate transcription of circadian target genes (3).…”

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confidence: 99%

Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney

Richards

All

Skopis

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1–3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes αENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPARα and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney.

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“…The decline in BP during sleep may be attributed in part to the Zeitgeber factors that reduce blood pressure and natriuresis by various molecular mechanisms [22,23]. A more general, physiological approach to this drop could be the decrease of sympathetic tone due to the body posture during sleep [24]. …”

Section: Discussionmentioning

confidence: 99%

How Protective Mechanisms Interact to Prevent Overnight Calcium Phosphate Precipitation - An Observational Study to Determine Factors Against Calcium Phosphate Lithogenesis in a Healthy Cohort

Shafiee

Logan²,

Halperin³

2016

Nephron

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Background/Aims: As restful, non-interrupted sleep is essential for normal mental and physical functioning, the urine flow rate (U_FR) overnight remains low. Due to this reduced U_FR, the kidneys produce a lower urine volume, which may lead to supersaturation of lithogens in the renal collecting system. The protective mechanisms that prevent the rise in the concentration of the lithogenic substances in urine, such as calcium phosphate, are explored. Methods: Urine samples were collected from 26 subjects every 2-3 h during daylight with one nocturnal collection; the U_FR was calculated in the median time for each collection period. Urinary constituents for calcium phosphate precipitation including electrolytes, calcium, phosphate, citrate, and pH were measured. Comparisons within individuals were done by paired t test. Results: The calcium excretion rate fell significantly overnight (from 2.4 ± 0.2 µmol/min during the daytime to 1.5 ± 0.3 µmol/min, p < 0.05), in parallel with sodium excretion (54 ± 16 µmol/min from its daytime 127 ± 12 µmol/min, p < 0.05), preventing nocturnal calcium concentration from increasing (3.0 ± 0.3 mmol/l daytime to 2.5 ± 0.5 mmol/l overnight), while citrate concentration did not change significantly. The total urine phosphate concentration rose significantly overnight (daytime 18.7 ± 1.4 µmol/min vs. nocturnal 20.9 ± 1.7 µmol/min), but the concentration of divalent phosphate did not increase in the overnight period. Conclusions: Although the U_FR was lower overnight, there was no evidence that the risk of calcium phosphate precipitate formation in healthy subjects was increased.

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Mechanism of the circadian clock in physiology

Cited by 117 publications

References 156 publications

Clock genes in hypertension

Clock genes in hypertension

Opposing actions of Per1 and Cry2 in the regulation of Per1 target gene expression in the liver and kidney

How Protective Mechanisms Interact to Prevent Overnight Calcium Phosphate Precipitation - An Observational Study to Determine Factors Against Calcium Phosphate Lithogenesis in a Healthy Cohort

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