• Molecules and Cells
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• 제40권7호
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• pp.450-456
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• 2017

Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-$erb{\alpha}$ induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

• Journal of the Korean Wood Science and Technology
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• 제50권5호
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• pp.338-352
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• 2022

Herein, water and ethanol extracts were obtained from the leaves, branches, kernels, and pericarp of Quercus gilva and subsequently analyzed for antioxidant activity and circadian rhythm regulation effects. Candidate components that may affect circadian rhythm and antioxidant activity were investigated to discover potential functional materials. Antioxidant activity was analyzed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity assays, showing that the hot water extract exhibited higher activity than that of the ethanol extract. In particular, the branch extract showed high antioxidant activity. By measuring total contents of polyphenols, flavonoids, and tannins, the hot water branch extract showed the highest concentrations, highlighting their significant contribution to the antioxidant activity. Examination of the circadian rhythm regulation of each extract showed that the ethanol extract exhibited greater impacts on the circadian rhythm amplitude compared to the water extract. The branch ethanol extract induced circadian rhythm amplitude changes via clock gene Bmal1 expression regulation. Determination of 12 phenolic compound concentrations showed that the branch ethanol extract contained many phenolic compounds, including catechin. This suggests that these com- pounds affected circadian rhythm regulation. In conclusion, the hot water branch extract has potential as an natural antioxidant material, while the corresponding ethanol extract has potential as a functional material for regulating circadian rhythm.

• Animal cells and systems
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• 제16권1호
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• pp.1-10
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• 2012

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

• Molecules and Cells
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• 제39권1호
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• pp.6-19
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• 2016

Redox signalling comprises the biology of molecular signal transduction mediated by reactive oxygen (or nitrogen) species. By specific and reversible oxidation of redoxsensitive cysteines, many biological processes sense and respond to signals from the intracellular redox environment. Redox signals are therefore important regulators of cellular homeostasis. Recently, it has become apparent that the cellular redox state oscillates in vivo and in vitro, with a period of about one day (circadian). Circadian timekeeping allows cells and organisms to adapt their biology to resonate with the 24-hour cycle of day/night. The importance of this innate biological timekeeping is illustrated by the association of clock disruption with the early onset of several diseases (e.g. type II diabetes, stroke and several forms of cancer). Circadian regulation of cellular redox balance suggests potentially two distinct roles for redox signalling in relation to the cellular clock: one where it is regulated by the clock, and one where it regulates the clock. Here, we introduce the concepts of redox signalling and cellular timekeeping, and then critically appraise the evidence for the reciprocal regulation between cellular redox state and the circadian clock. We conclude there is a substantial body of evidence supporting circadian regulation of cellular redox state, but that it would be premature to conclude that the converse is also true. We therefore propose some approaches that might yield more insight into redox control of cellular timekeeping.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2004년도 춘계학술발표대회
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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)

• Journal of Photoscience
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• 제9권2호
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• pp.25-28
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• 2002

The chicken pineal gland has been used for studies on the circadian clock, because it retains an intracellular phototransduction pathway regulating the phase of the intrinsic clock oscillator. Previously, we identified chicken clock genes expressed in the gland (cPer2, cPer3, cBmal1, cBmal2, cCry1, cCry2, and cClock), and showed that a cBMALl/2-cCLOCK heteromer acts as a regulator transactivating cPer2 gene through the CACGTG E-box element found in its promoter. Notably, mRNA expression of cPer2 gene is up-regulated by light as well as is driven by the circadian clock, implying that light-dependent clock resetting may involve the up-regulation of cPer2 gene. To explore the mechanism of light-dependent gene expression unidentified in animals, we first focused on pinopsin gene whose mRNA level is also up-regulated by light. A pinopsin promoter was isolated and analyzed by transcriptional assays using cultured chicken pineal cells, resulting in identification of an 18-bp light-responsive element that includes a CACGTG E-box sequence. We also investigated a role of mitogen-activated protein kinase (MAPK) in the clock resetting, especially in the E-box-dependent transcriptional regulation, because MAPK is phospholylated (activated) in a circadian manner and is rapidly dephosphorylated by light in the gland. Both pulldown analysis and kinase assay revealed that MAPK directly associates with BMAL1 to phosphorylate it at several Ser/Thr residues. Transcriptional analyses implied that the MAPK-mediated phosphorylation may negatively regulate the BMAL-CLOCK-dependent transactivation through the E-box. These results suggest that the CACGTG E-box serves not only as a clock-controlled element but also as a light-responsive element.

• 생명과학회지
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• 제27권10호
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• pp.1225-1231
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• 2017

암을 포함한 다양한 인간의 질병 발생이 circadian clock 유전자의 변형된 발현 양상과 깊은 연관관계를 나타내고 있다. 세포 주기와 세포 성장은 circadian rhythm과 연결되어 있으며, 이를 조절하는 clock 유전자의 비정상적인 발현은 결국 종양 발생과 암의 발달을 유발하게 된다. Circadian clock에 관한 분자적 기전은 다수의 clock activator와 clock repressor의 통합적인 조절에 따른 전사 및 번역이 포함된 음성피드백 고리로 구성되어 있다. 이러한 circadian rhythm의 자동조절 기전에 의해 전체 유전체의 약 10~15%가 전사 수준에서 영향받는 것으로 나타났다. 많은 clock 유전자들 중, Period 1 (Per1)과 Period 2 (Per2)는 clock repressor 유전자로 정상적인 생리적 리듬을 조절하는 것에 기여한다. PER1과 PER2는 cyclin, CDK, CKI를 포함하는 세포 주기 조절자의 발현에 관여함이 밝혀졌으며, 다양한 암에서 PER1과 PER2의 발현 감소가 보고되었다. 따라서, 본 논문에서는 PER1과 PER2의 circadian rhythm에서의 분자적 기능과 종양 발생과 관련된 PER1과 PER2의 하위 표적인자에 대해 살펴보고, 암 치료를 위한 새로운 치료 표적과 암의 예후를 예측하기 위한 분자 지표로써의 PER1과 PER2의 가능성에 대해 서술하고자 한다.

• 생명과학회지
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• 제23권8호
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• pp.1064-1072
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• 2013

일주기 리듬은 모든 살아있는 유기체의 생리현상을 지배하는 호르몬의 변화에 의해서 조절된다. 포유동물에서 송과체의 주된 기능은 시상 하부 시교차 상핵에서 발생되는 일주기 리듬을 주로 어두울 때 증가하는 순환성 멜라토닌의 리듬 신호로 변화시키는 것이다. 송과체는 직접적인 광감도는 없지만, 망막신경절세포로 하부조직을 포함하는 멀티 시냅스 경로를 통하여 빛에 반응한다. 주기적인 리듬 조절은 주위환경의 빛과 멜라토닌 생성의 리듬조절 효소인 arylalkylamine-N-acetyltransferase (AANAT)의 발현과 긴밀한 관계를 통해 이루어진다. 이전 실험에서 AANAT 단백질이 어두울 때의 발현이 전사 조절, 전사 후 조절, 번역 후 조절 메커니즘으로 설명되었다. AANAT 단백질 발현에 관한 분자적 기전은 멜라토닌의 일주기 리듬에 대한 새로운 견해를 제공한다. 광범위한 동물 연구에서 많은 포유류의 계절 리듬을 위한 송과체 멜라토닌은 일주기 리듬의 조절과 수면 조절에 관련이 있는 것으로 알려졌다. 이것은 시차증이나 교대 근무 수면 장애와 같은 일주기 리듬 수면 장애를 치료하는 데 있어서 가치가 있다. 또한 멜라토닌은 다른 영역에도 영향을 미치는데 특히 몸의 생리적 기능을 조절하는데 영향을 미친다. 게다가 정신의학적 질환뿐 만 아니라 생식기 질환, 심혈관 질환, 면역 조절 질환도 이 호르몬에 의해 영향을 받는 것으로 밝혀졌다.

• BMB Reports
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• 제48권12호
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• pp.677-684
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• 2015

Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells and activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca²⁺ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.

• 생명과학회지
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• 제7권3호
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• pp.205-211
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• 1997

수수에서 식물호르몬 에틸렌 생합성은 circadin 리듬 현상을 보인다고 이미 보고된바 있다. 따라서 본 실험은 또 다른 식물호르몬 지베렐린 생합성도 에틸렌과 같은 circadin 리듬 현상을 보이는지를 조사한 결과를 요약하면 다음과 같다. 일정기간 동안 12시간 주기의 밤과 낮 조건에서 생육시킨 식물체를 연속광조건으로 옮긴후 매 시간 마다 지베렐린의 함량변화를 조사하였다. 1. GA$_{12}$는 공시한 두 품종 모두에서 뚜렸한 circadin 리듬현상을 보였다. 2. GA$_{53}$과 GA$_{19}$는 일체의 리듬현상을 보이지 않았다. 3. GA$_{20}$과 GA$_{1}$은 circadin 리듬현상을 보였지만 연속광하에서 리듬의 정도는 12시간 주기의 정상적인 일장하에 비해 현저히 감소하였다. 4. 수수의 개화는 원적외선광의 조사에 의해 촉진됨에도 불구하고 이들 처리는 내생지베렐린의 함량을 변화시키지 않았다.