• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.261-261
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• 2004

Circadian rhythms, which measure time about 24 hours, are generated by one of the most ubiquitous and well investigated timing system. More recently, circadian clock gene expression has been reported in various peripheral tissues. If a circadian clock is functioning in the testis, expression of clock genes should be observed in this tissue. To resolve this issue, we examined the expression of circadian clock genes in the testis. (omitted)

• Molecules and Cells
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• v.22 no.3
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• pp.285-290
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• 2006

The light sensing system in the eye directly affects the circadian oscillator in the mammalian suprachiasmatic nucleus (SCN). To investigate this relationship in the rat, we examined the circadian expression of clock genes in the SCN and eye tissue during a 24 h day/night cycle. In the SCN, rPer1 and rPer2 mRNAs were expressed in a clear circadian rhythm like rCry1 and rCry2 mRNAs, whereas the level of BMAL1 and CLOCK mRNAs decreased during the day and increased during the night with a relatively low amplitude. It seems that the clock genes of the SCN may function in response to a master clock oscillation in the rat. In the eye, the rCry1 and rCry2 were expressed in a circadian rhythm with an increase during subjective day and a decrease during subjective night. However, the expression of Opn4 mRNA did not exhibit a clear circadian pattern, although its expression was higher in daytime than at night. This suggests that cryptochromes located in the eye, rather than melanopsin, are the major photoreceptive system for synchronizing the circadian rhythm of the SCN in the rat.

• Molecules and Cells
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• v.28 no.2
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• pp.75-80
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• 2009

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.

• Molecules and Cells
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• v.23 no.2
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• pp.145-153
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• 2007

Elucidation of the roles of circadian associated factors requires a better understanding of the molecular mechanisms of circadian rhythms, control of flowering time through photoperiodic pathways, and photosensory signal transduction. In Arabidopsis, the APRR1 quintet, APRRs 1, 3, 5, 7, and 9, are known as central oscillator genes. Other plants may share the molecular mechanism underlying the circadian rhythm. To identify and characterize these circadian response genes in Brassica crops whose genome was triplicated after divergence from Arabidopsis, we identified B. rapa BAC clones containing these genes by BLAST analysis of B. rapa BAC end sequences against the five corresponding Arabidopsis regions. Subsequent fingerprinting, Southern hybridization, and PCR allowed identification of five BAC clones, one for each of the five circadian-related genes. By draft shotgun sequencing of the BAC clones, we identified the complete gene sequences and cloned the five expressed B. rapa circadian-associated gene members, BrPRRs 1, 3, 5, 7, and 9. Phylogenetic analysis revealed that each BrPRR was orthologous to the corresponding APRR at the sequence level. Northern hybridization revealed that the five genes were transcribed at distinct points in the 24 hour period, and Southern hybridization revealed that they are present in 2, 1, 2, 2, and 1 copies, respectively in the B. rapa genome, which was triplicated and then diploidized during the last 15 million years.

• Journal of Korean Biological Nursing Science
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• v.18 no.4
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• pp.305-317
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• 2016

Purpose: Recent studies demonstrated disruption of the circadian clock gene is associated with the development of obesity and metabolic syndrome. Obesity is often caused by the high calorie intake, In addition, the chronic stress tends to contribute to the increased risk for obesity. To evaluate the molecular mechanisms, we examined the expression of circadian clock genes in high fat diet-induced mice models with the chronic stress. Methods: C57BL/6J mice were fed with a 45% or 60% high fat diet for 8 weeks. Daily immobilization stress was applied to mice fed with a 45% high fat for 16 weeks. We compared body weight, food consumption, hormone levels and metabolic variables in blood. mRNA expression levels of metabolic and circadian clock genes in both fat and liver were determined by quantitative RT-PCR. Results: The higher fat content induced more severe hyperglycemia, hyperlipidemia and hyperinsulinemia, and these results correlated with their relevant gene expressions in fat and liver tissues. Chronic stress had only minimal effects on metabolic variables, but it altered the expression patterns of metabolic and circadian clock genes. Conclusion: These results suggest that the fat metabolism regulates the function of the circadian clock genes in peripheral tissues, and stress hormones may contribute to its regulation.

• Journal of Life Science
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• v.27 no.10
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• pp.1225-1231
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• 2017

Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

• Animal cells and systems
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• v.16 no.1
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• pp.27-33
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• 2012

The suprachiasmatic nucleus (SCN) of the teleost hypothalamus contains a central circadian pacemaker, which adjusts circadian rhythms within the body to environmental light-dark cycles. It has been shown that exposure to darkness during the day causes phase shifts in circadian rhythms. In this study, we examined the effect of exposure to darkness on the mRNA expression levels of two circadian clock genes, namely, $Period2$ ($Per2$) and $Cryptochrome1$ ($Cry1$), and the rate-limiting enzyme in melatonin synthesis, arylalkylamine $N$-acetyltransferase-2 (Aanat2), in the pineal gland of olive flounder, $Paralichthys$ $olivaceus$. The expression of these genes showed circadian variations and was significantly higher during the dark phase. These changes may be involved in the mechanism of dark-induced phase shifts. Furthermore, this study suggests that olive flounder may be a teleost model to investigate the localization and function of circadian oscillators.

• Animal cells and systems
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• v.9 no.3
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• pp.153-160
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• 2005

Most living organisms exhibit the circadian rhythm in their physiology and behavior. Recent identification of several clock genes in mammals has led to the molecular understanding of how these components generate and maintain the circadian rhythm. Many reports have implicated the photic induction of either mPer1 or mPer2 in the hypothalamic region called the suprachiasmatic nucleus (SCN) to phase shift the brain clock. It is now established that peripheral tissues other than the brain also express these clock genes and that the clock machinery in these tissues work in a similar way to the SCN clock. To determine the role of the two canonical clock genes, mPer1 and mPer2, in the peripheral clock shift, stable HEK293EcR cell lines that can be induced and stably express these proteins were prepared. By regulating the expression of these proteins, it could be shown that induction of the clock genes, either mPer1 or mPer2 alone is not sufficient to cause clock phase shifting in these cells. Our real-time PCR analysis on these cells indicates that the induction of mPER proteins dampens the expression of the clock-specific transcription factor mBmal1. Altogether, our present data suggest that mPer1 and mPer2 may not function in clock shift or take part in differential roles on the peripheral circadian clock.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.358-367
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• 2018

Most organisms have adapted to a circadian rhythm that follows a roughly 24-hour cycle, which is modulated by both internal (clock-related genes) and external (environment) factors. In such organisms, the central nervous system (CNS) is influenced by the circadian rhythm of individual cells. Furthermore, the period circadian clock 2 (Per2) gene is an important component of the circadian clock, which modulates the circadian rhythm. Per2 is mainly expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as other brain areas, including the midbrain and forebrain. This indicates that Per2 may affect various neurobiological activities such as sleeping, depression, and addiction. In this review, we focus on the neurobiological functions of Per2, which could help to better understand its roles in the CNS.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.31-40
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• 2021

All living beings on earth have an important mechanism of 24-h periodicity, which controls their physiology, metabolism, and behavior. In humans, 24-h periodicity is regulated by the superchiasmatic nucleus (SCN) through external and environmental cues. Peripheral organs demonstrate circadian rhythms and circadian clock functions, and these are also observed in cultured cell lines. Every cell contains a CLOCK: BMAL1 loop for the generation of circadian rhythms. In this review, we focused on cell autonomous circadian rhythms in immune cells, the inflammatory diseases caused by disruption of circadian rhythms in hormones, and the role of clock genes in inflammatory diseases.