Chronic treatment with a selective inhibitor of casein kinase I δ/ε yields cumulative phase delays in circadian rhythms

Sprouse, Jeffrey; Reynolds, Linda; Kleiman, Robin J.; Tate, Barbara; Swanson, Terri A.; Pickard, Gary E.

doi:10.1007/s00213-010-1860-5

Cited by 26 publications

(19 citation statements)

References 46 publications

(57 reference statements)

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“…As previously mentioned, CK1␦/ε inhibition impairs the circadian clock through induction of phase delays in rats under free running conditions (7). Cynomolgus monkeys also display a similar phase delay (39), and time of dosing affects the phase shifting (38). In addition to this role in regulation of the Fig.…”

Section: Discussionmentioning

confidence: 92%

Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε

Richards

Greenlee

Jeffers

et al. 2012

American Journal of Physiology-Renal Physiology

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Increasing evidence suggests that the circadian clock plays an important role in the control of renal function and blood pressure. We previously showed that the circadian clock protein Period (Per)1, positively regulates the expression of the rate limiting subunit of the renal epithelial sodium channel (αENaC), which contributes to blood pressure regulation. Casein kinases 1δ and 1ε (CK1δ/ε) are critical regulators of clock proteins. CK1δ/ε must phosphorylate the circadian clock protein Per1 in order for the latter to enter the nucleus. We used a commercially available CK1δ/ε inhibitor, PF670462, to test the effect of CK1δ/ε blockade and inhibited Per1 nuclear entry on αENaC in a model of the renal cortical collecting duct (mpkCCD(c14) cells). CK1δ/ε blockade prevented Per1 and Clock from interacting with an E-box from the αENaC promoter. CK1δ/ε inhibition reduced αENaC mRNA levels by <60%. A similar decrease in αENaC mRNA was observed following siRNA-mediated CK1δ/ε knock-down. Inhibition of CK1δ/ε effectively prevented the transcriptional response of αENaC to aldosterone, suggesting an interaction between the circadian clock and aldosterone-mediated regulation of αENaC. CK1δ/ε inhibition significantly reduced αENaC but increased Caveolin-1 membrane protein levels; transepithelial current, a measure of ENaC activity, was decreased. Importantly, single channel analysis in amphibian renal cells demonstrated a dramatic decrease in the number of patches with observable ENaC current following CK1δ/ε inhibition. The present study shows for the first time that CK1δ/ε inhibition and impaired Per1 nuclear entry results in decreased αENaC expression and ENaC activity, providing further support for direct control of ENaC by the circadian clock.

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Section: Discussionmentioning

confidence: 92%

Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε

Richards

Greenlee

Jeffers

et al. 2012

American Journal of Physiology-Renal Physiology

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“…An inhibitor specific for CK1ε (PF-4800567) has only a slight effect on the period of oscillating rat-1 fibroblasts stably transfected with a Per2::luc reporter compared to the dual CK1δ/ε inhibitor (PF-670462) which causes an increase in fibroblast circadian period (Walton et al ., 2009). Single injections into rats of the dual CK1δ/ε inhibitor induce large phase delays in circadian locomotor rhythms under free-running and entrained conditions (Badura et al ., 2007; Sprouse et al ., 2010). Daily treatment with PF-670462 significantly lengthens locomotor behavioral rhythms in a dose-dependent manner in wild-type, CK1 ε tau , and CK1ε −/− mice (Meng et al ., 2010).…”

Section: Posttranslational Modification Of Clock Proteinsmentioning

confidence: 99%

Genetics of Circadian Rhythms in Mammalian Model Organisms

Lowrey

Takahashi

2011

Advances in Genetics

499

429

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The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal.

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“…Both isoforms belong to the superfamily of serine/threonine-specific kinases that play a major role in regulating and sustaining the pace of the molecular clock by phosphorylating circadian proteins, BMAL1, CRY, PER1 and PER2 (Eide, Kang, Crapo, Gallego, & Virshup, 2005; Meng et al, 2008). PER2 is rhythmically destabilized by CK1 ε / δ phosphorylation (Eide et al, 2005; Etchegaray et al, 2009; Meng et al, 2008), and pharmacological inhibition of CK1 ε / δ induces phase delays of circadian locomotor activity, enhances PER2 protein levels, and inhibits nuclear translocation of PER3 (Badura et al, 2007; Sprouse et al, 2010). CK1 ε / δ inhibition also inhibits PER3 nuclear translocation (Sprouse et al, 2010).…”

Section: Circadian Gene Mutations and Alcohol Seeking And Rewardmentioning

confidence: 99%

“…PER2 is rhythmically destabilized by CK1 ε / δ phosphorylation (Eide et al, 2005; Etchegaray et al, 2009; Meng et al, 2008), and pharmacological inhibition of CK1 ε / δ induces phase delays of circadian locomotor activity, enhances PER2 protein levels, and inhibits nuclear translocation of PER3 (Badura et al, 2007; Sprouse et al, 2010). CK1 ε / δ inhibition also inhibits PER3 nuclear translocation (Sprouse et al, 2010). CK1 ε / δ is associated with behavioral responses to other drugs of abuse (Bryant et al, 2009; Bryant et al, 2012).…”

Section: Circadian Gene Mutations and Alcohol Seeking And Rewardmentioning

confidence: 99%

Circadian rhythms and addiction: Mechanistic insights and future directions.

Logan

Williams

McClung

2014

Behavioral Neuroscience

123

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Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction.

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Chronic treatment with a selective inhibitor of casein kinase I δ/ε yields cumulative phase delays in circadian rhythms

Cited by 26 publications

References 46 publications

Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε

Inhibition of αENaC expression and ENaC activity following blockade of the circadian clock-regulatory kinases CK1δ/ε

Genetics of Circadian Rhythms in Mammalian Model Organisms

Circadian rhythms and addiction: Mechanistic insights and future directions.

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