Heavy Water Lengthens the Molecular Circadian Clock Period in the Suprachiasmatic Nucleus of Mice In Vitro

Heavy water lengthens the periods of circadian rhythms in various plant and animal species. Many studies have reported that drinking heavy water lengthens the periods of circadian activity rhythms of rodents by slowing the clock mechanism in the suprachiasmatic nucleus (SCN), the mammalian circadian center. The SCN clock is stable and robust against disturbance, due to its intercellular network. It is unclear whether this robustness provides resistance to the effects of heavy water. Here, we report that heavy water lengthened the rhythm period of clock gene expression of the SCN and peripheral tissues in vitro using a PERIOD2::LUCIFERASE bioluminescence reporter. Our results show that the period-elongation rate of the SCN is similar to those of other tissues. Therefore, the intercellular network of the SCN is not resistant to the period-elongation effect of heavy water.

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Temporal profile of circadian clock gene expression in a transplanted suprachiasmatic nucleus and peripheral tissues

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2007.05926.x ◽

2007 ◽

Vol 26 (10) ◽

pp. 2731-2738 ◽

Cited By ~ 9

Author(s):

Mitsugu Sujino ◽

Mamoru Nagano ◽

Atsuko Fujioka ◽

Yasufumi Shigeyoshi ◽

Shin-Ichi T. Inouye

Keyword(s):

Gene Expression ◽

Circadian Clock ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Circadian Clock Gene ◽

Peripheral Tissues ◽

Temporal Profile ◽

Clock Gene Expression

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CDK1 and CDK2 regulate phosphorylation-dependent NICD1 turnover and the periodicity of the segmentation clock

10.1101/245704 ◽

2018 ◽

Cited By ~ 1

Author(s):

Francesca Anna Carrieri ◽

Philip Murray ◽

Paul Davies ◽

Jacqueline Kim Dale

Keyword(s):

Clock Gene ◽

Dependent Manner ◽

Clock Period ◽

Segmentation Clock ◽

Clock Gene Expression ◽

Notch Intracellular Domain ◽

Somite Formation ◽

Cycle Dependent

ABSTRACTAll vertebrates share a segmented body axis. Segments form periodically from the rostral end of the presomitic mesoderm (PSM) and this periodicity is regulated by the segmentation clock, a molecular oscillator that drives dynamic clock gene expression across the PSM with a periodicity that matches somite formation. Notch signalling is crucial to this process. Altering Notch intracellular domain (NICD) stability affects both the clock period and somite size. However, the mechanistic details of how NICD stability is regulated are unclear.We identified a highly conserved site crucial for NICD recognition by the SCF E3 ligase, which targets NICD for degradation. We demonstrate both CDK1 and CDK2 can phosphorylate NICD in the domain where this crucial residue lies and that NICD levels vary in a cell cycle-dependent manner. Inhibiting CDK1 or CDK2 activity increases NICD levels both in vitro and in vivo, leading to a delay of clock gene oscillations.

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Bimodal Clock Gene Expression in Mouse Suprachiasmatic Nucleus and Peripheral Tissues Under a 7-Hour Light and 5-Hour Dark Schedule

Journal of Biological Rhythms ◽

10.1177/0748730406295435 ◽

2007 ◽

Vol 22 (1) ◽

pp. 58-68 ◽

Cited By ~ 32

Author(s):

Tsuyoshi Watanabe ◽

Emiko Naito ◽

Nobuhiro Nakao ◽

Hajime Tei ◽

Takashi Yoshimura ◽

...

Keyword(s):

Gene Expression ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Peripheral Tissues ◽

Clock Gene Expression

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Time-lapse confocal imaging of clock gene expression and calcium in neuronal networks of suprachiasmatic nucleus

Neuroscience Research ◽

10.1016/j.neures.2011.07.225 ◽

2011 ◽

Vol 71 ◽

pp. e53

Author(s):

Ryosuke Enoki ◽

Shigeru Kuroda ◽

Daisuke Ono ◽

Tetsuo Ueda ◽

Hasan Mazhir ◽

...

Keyword(s):

Gene Expression ◽

Suprachiasmatic Nucleus ◽

Neuronal Networks ◽

Clock Gene ◽

Time Lapse ◽

Confocal Imaging ◽

Clock Gene Expression

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Dynamics of the Adjustment of Clock Gene Expression in the Rat Suprachiasmatic Nucleus to an Asymmetrical Change from a Long to a Short Photoperiod

Journal of Biological Rhythms ◽

10.1177/0748730407301052 ◽

2007 ◽

Vol 22 (3) ◽

pp. 259-267 ◽

Cited By ~ 11

Author(s):

Alena Sumová ◽

Zuzana Kováčiková ◽

Helena Illnerová

Keyword(s):

Gene Expression ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Short Photoperiod ◽

Clock Gene Expression

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Phase-dependent induction by light of rat Clock gene expression in the suprachiasmatic nucleus

Molecular Brain Research ◽

10.1016/s0169-328x(99)00031-5 ◽

1999 ◽

Vol 66 (1-2) ◽

pp. 104-110 ◽

Cited By ~ 26

Author(s):

Hiroshi Abe ◽

Sato Honma ◽

Masakazu Namihira ◽

Yusuke Tanahashi ◽

Masaaki Ikeda ◽

...

Keyword(s):

Gene Expression ◽

Suprachiasmatic Nucleus ◽

Clock Gene ◽

Clock Gene Expression

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Clock Gene Expression in the Submandibular Glands

Journal of Dental Research ◽

10.1177/154405910508401219 ◽

2005 ◽

Vol 84 (12) ◽

pp. 1193-1197 ◽

Cited By ~ 20

Author(s):

M. Furukawa ◽

T. Kawamoto ◽

M. Noshiro ◽

K.K. Honda ◽

M. Sakai ◽

...

Keyword(s):

Salivary Gland ◽

Salivary Glands ◽

Clock Gene ◽

Clock Genes ◽

Expression Profiles ◽

Mrna Levels ◽

Peripheral Tissues ◽

Submandibular Glands ◽

Circadian Expression ◽

Clock Gene Expression

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

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The disruption of circadian clockwork in differentiating cells from rat reproductive tissues as identified by in vitro real-time monitoring system

Journal of Endocrinology ◽

10.1677/joe-07-0044 ◽

2007 ◽

Vol 193 (3) ◽

pp. 413-420 ◽

Cited By ~ 45

Author(s):

Pei-Jian He ◽

Masami Hirata ◽

Nobuhiko Yamauchi ◽

Seiichi Hashimoto ◽

Masa-aki Hattori

Keyword(s):

Gene Expression ◽

Real Time ◽

Monitoring System ◽

Cell Types ◽

Luciferase Reporter ◽

Luciferase Reporter Gene ◽

Peripheral Tissues ◽

Reproductive Tissues ◽

Clock Gene Expression

The circadian clock, regulating hormonal secretion and metabolisms in accordance with the environmental light–dark cycle, resides in almost all peripheral tissues as well as in the superchiasmatic nucleus. Clock gene expression has been found to be noncyclic during spermatogenesis and the differentiation of thymocytes. However, currently little is known about how cell differentiation could affect circadian clockwork. We performed this study using the in vitro real-time oscillation monitoring system to examine the clockwork in several types of differentiating cells originated from reproductive tissues of transgenic rats (constructed with Period gene 2 (Per2) promoter-destabilized luciferase reporter gene). After treatment with dexamethasone (DXM), persistent oscillation of Per2 expression was observed in both gonadotropin-induced and pregnant ovarian luteal cells, proliferative uterine stromal cells (USCs), and nondifferentiating testicular interstitial cells, with a cyclic period of ~24 h. In contrast to these cell types, only one cycle of oscillation was sustained in granulosa cells undergoing differentiation. Additionally, Per2 oscillation was irregular in USCs undergoing decidualization induced by medroxyprogesterone acetate plus N6, 2-O-dibutyryl adenosine 3′:5′-cyclic monophosphate. Furthermore, no oscillation of Per2 expression was evoked by DXM in Leydig cells and thymocytes. In conclusion, the present study characterized the oscillation of Per2 gene expression in several types of ovarian, uterine, and testicular cells, and it is strongly suggested that circadian clockwork is affected during cellular differentiation.

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