Physiological and pathophysiological role of the circadian clock system

2012 ◽  
Vol 153 (35) ◽  
pp. 1370-1379 ◽  
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Biological Processes ◽  
Metabolic Processes ◽  
Hypothalamic Region ◽  
Clock System ◽  
Treatment And Prevention ◽  
Exact Function ◽  
Essential Components ◽  
Master Clock

It has been well known for ages that in living organisms the rhythmicity of biological processes is linked to the ~ 24-hour light–dark cycle. However, the exact function of the circadian clock system has been explored only in the past decades. It came to light that the photosensitive primary “master clock” is situated in the suprachiasmatic photosensitive nuclei of the special hypothalamic region, and that it is working according to ~24-hour changes of light and darkness. The master clock sends its messages to the peripheral “slave clocks”. In many organs, like pancreatic β-cells, the slave clocks have autonomic functions as well. Two essential components of the clock system are proteins encoded by the CLOCK and BMAL1 genes. CLOCK genes are in interaction with endonuclear receptors such as peroxisoma-proliferator activated receptors and Rev-erb-α, as well as with the hypothalamic-pituitary-adrenal axis, regulating the adaptation to stressors, energy supply, metabolic processes and cardiovascular system. Melatonin, the product of corpus pineale has a significant role in the functions of the clock system. The detailed discovery of the clock system has changed our previous knowledge about the development of many diseases. The most explored fields are hypertension, cardiovascular diseases, metabolic processes, mental disorders, cancers, sleep apnoe and joint disorders. CLOCK genes influence ageing as well. The recognition of the periodicity of biological processes makes the optimal dosing of certain drugs feasible. The more detailed discovery of the interaction of the clock system might further improve treatment and prevention of many disorders. Orv. Hetil., 2012, 153, 1370–1379.

Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5

2021 ◽  
Author(s):  
Jing Zhang ◽  
Lijia Zhao ◽  
Yating Li ◽  
Hao Dong ◽  
Haisen Zhang ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Clock Genes ◽  
Expression Patterns ◽  
Current Data ◽  
Orphan Receptor ◽  
Luciferase Reporter ◽  
Mobility Shift ◽  
Rhythmic Expression ◽  
Clock System ◽  
Circadian Clock Genes

Autophagy of granulosa cells (GCs) is involved in follicular atresia, which occurs repeatedly during the ovarian development cycle. Several circadian clock genes are rhythmically expressed in both rodent ovarian tissues and GCs. Nuclear receptor subfamily 1 group D member 1 (NR1D1), an important component of the circadian clock system, is involved in the autophagy process through the regulation of autophagy-related genes. However, there are no reports illustrating the role of the circadian clock system in mouse GC autophagy. In the present study, we found that core circadian clock genes (Bmal1, Per2, Nr1d1, and Dbp) and an autophagy-related gene (Atg5) exhibited rhythmic expression patterns across 24 h in mouse ovaries and primary GCs. Treatment with SR9009, an agonist of NR1D1, significantly reduced the expression of Bmal1, Per2, and Dbp in mouse GCs. ATG5 expression was significantly attenuated by SR9009 treatment in mouse GCs. Conversely, Nr1d1 knockdown increased ATG5 expression in mouse GCs. Decreased NR1D1 expression at both the mRNA and protein levels was detected in the ovaries of Bmal1-/- mice, along with elevated expression of ATG5. Dual-luciferase reporter assay and electrophoretic mobility shift assay showed that NR1D1 inhibited Atg5 transcription by binding to two putative retinoic acid-related orphan receptor response elements within the promoter. In addition, rapamycin-induced autophagy and ATG5 expression were partially reversed by SR9009 treatment in mouse GCs. Taken together, our current data demonstrated that the circadian clock regulates GC autophagy through NR1D1-mediated inhibition of ATG5 expression, and thus, plays a role in maintaining autophagy homeostasis in GCs.

scholarly journals Functional Role of CREB-Binding Protein in the Circadian Clock System of Drosophila melanogaster

2007 ◽  
Vol 27 (13) ◽  
pp. 4876-4890 ◽  
Author(s):  
Chunghun Lim ◽  
Jongbin Lee ◽  
Changtaek Choi ◽  
Juwon Kim ◽  
Eunjin Doh ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Cultured Cells ◽  
Clock Genes ◽  
Binding Protein ◽  
Clock Cycle ◽  
Creb Binding Protein ◽  
Locomotor Rhythm ◽  
Pigment Dispersing Factor ◽  
Clock System ◽  
Functional Relevance

ABSTRACT Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system. Cellular factors that contain histone acetyltransferase and histone deacetylase activity have been implicated in these processes by direct interactions with clock genes, but their functional relevance remains to be assessed by use of appropriate animal models. Here, using transgenic fly models, we show that CREB-binding protein (CBP) participates in the transcriptional regulation of the Drosophila CLOCK/CYCLE (dCLK/CYC) heterodimer. CBP knockdown in pigment dispersing factor-expressing cells lengthens the period of adult locomotor rhythm with the prolonged expression of period and timeless genes, while CBP overexpression in timeless-expressing cells causes arrhythmic circadian behaviors with the impaired expression of these dCLK/CYC-induced clock genes. In contrast to the mammalian circadian clock system, CBP overexpression attenuates the transcriptional activity of the dCLK/CYC heterodimer in cultured cells, possibly by targeting the PER-ARNT-SIM domain of dCLK. Our data suggest that the Drosophila circadian clock system has evolved a distinct mechanism to tightly regulate the robust transcriptional potency of the dCLK/CYC heterodimer.

scholarly journals Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chao Song ◽  
Jia Wang ◽  
Brett Kim ◽  
Chanyi Lu ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Bone Metabolism ◽  
Clock Genes ◽  
Current Knowledge ◽  
Gene Knockout ◽  
Osteoclast Differentiation ◽  
Clock System ◽  
Peripheral Oscillators ◽  
Turnover Markers

Numerous physiological processes of mammals, including bone metabolism, are regulated by the circadian clock system, which consists of a central regulator, the suprachiasmatic nucleus (SCN), and the peripheral oscillators of the BMAL1/CLOCK-PERs/CRYs system. Various bone turnover markers and bone metabolism-regulating hormones such as melatonin and parathyroid hormone (PTH) display diurnal rhythmicity. According to previous research, disruption of the circadian clock due to shift work, sleep restriction, or clock gene knockout is associated with osteoporosis or other abnormal bone metabolism, showing the importance of the circadian clock system for maintaining homeostasis of bone metabolism. Moreover, common causes of osteoporosis, including postmenopausal status and aging, are associated with changes in the circadian clock. In our previous research, we found that agonism of the circadian regulators REV-ERBs inhibits osteoclast differentiation and ameliorates ovariectomy-induced bone loss in mice, suggesting that clock genes may be promising intervention targets for abnormal bone metabolism. Moreover, osteoporosis interventions at different time points can provide varying degrees of bone protection, showing the importance of accounting for circadian rhythms for optimal curative effects in clinical treatment of osteoporosis. In this review, we summarize current knowledge about circadian rhythms and bone metabolism.

scholarly journals The BrGI Circadian Clock Gene Is Involved in the Regulation of Glucosinolates in Chinese Cabbage

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1664
Author(s):  
Nan-Sun Kim ◽  
Su-Jeong Kim ◽  
Jung-Su Jo ◽  
Jun-Gu Lee ◽  
Soo-In Lee ◽  
...  
Keyword(s):  
Transgenic Plants ◽  
Circadian Clock ◽  
Brassica Rapa ◽  
Chinese Cabbage ◽  
Clock Gene ◽  
Clock Genes ◽  
Floral Induction ◽  
Stem Elongation ◽  
Circadian Clock Gene ◽  
Clock System

Circadian clocks integrate environmental cues with endogenous signals to coordinate physiological outputs. Clock genes in plants are involved in many physiological and developmental processes, such as photosynthesis, stomata opening, stem elongation, light signaling, and floral induction. Many Brassicaceae family plants, including Chinese cabbage (Brassica rapa ssp. pekinensis), produce a unique glucosinolate (GSL) secondary metabolite, which enhances plant protection, facilitates the design of functional foods, and has potential medical applications (e.g., as antidiabetic and anticancer agents). The levels of GSLs change diurnally, suggesting a connection to the circadian clock system. We investigated whether circadian clock genes affect the biosynthesis of GSLs in Brassica rapa using RNAi-mediated suppressed transgenic Brassica rapa GIGENTEA homolog (BrGI knockdown; hereafter GK1) Chinese cabbage. GIGANTEA plays an important role in the plant circadian clock system and is related to various developmental and metabolic processes. Using a validated GK1 transgenic line, we performed RNA sequencing and high-performance liquid chromatography analyses. The transcript levels of many GSL pathway genes were significantly altered in GK1 transgenic plants. In addition, GSL contents were substantially reduced in GK1 transgenic plants. We report that the BrGI circadian clock gene is required for the biosynthesis of GSLs in Chinese cabbage plants.

scholarly journals Effect of Circadian Rhythm on Metabolic Processes and the Regulation of Energy Balance

2019 ◽  
Vol 74 (4) ◽  
pp. 322-330 ◽  
Author(s):  
Yeliz Serin ◽  
Nilüfer Acar Tek
Keyword(s):  
Circadian Rhythm ◽  
Energy Balance ◽  
Circadian Clock ◽  
Crucial Role ◽  
Hormone Secretion ◽  
Biological Processes ◽  
Metabolic Processes ◽  
Circadian Timing ◽  
Timing System ◽  
Circadian Timing System

Background: The circadian timing system or circadian clock plays a crucial role in many biological processes, such as the sleep-wake cycle, hormone secretion, cardiovascular health, glucose homeostasis, and body temperature regulation. Energy balance is also one of the most important cornerstones of metabolic processes, whereas energy imbalance is associated with many diseases (i.e., obesity, diabetes, cardiovascular disease). Circadian clock is the main regulator of metabolism, and this analysis provides an overview of the bidirectional effect of circadian rhythm on metabolic processes and energy balance. Summary: The circadian timing system or circadian clock plays a crucial role in many biological processes, but the increase in activities that operate 24/7 and the common usage of television, internet, and mobile phones almost 24 h a day leads to a gradual decrease in the adequate sleeping time. According to recent research, long-term circadian disruptions are associated with many pathological conditions such as premature mortality, obesity, impaired glucose tolerance, diabetes, psychiatric disorders, anxiety, depression, and cancer progression, whereas short-term disruptions are associated with impaired wellness, fatigue, and loss of concentration. In this review, the circadian rhythm in metabolic processes and their effect on energy balance were examined. Key Messages: Circadian rhythm has a bidirectional interaction with almost all metabolic processes. Therefore, understanding the main reason affecting the circadian clock and creating treatment guidelines using circadian rhythm may increase the success of disease treatment. Chronopharmacology, chrononutrition, and chronoexercise are the novel treatment approaches in metabolic balance.

scholarly journals The role of the circadian clock system in nutrition and metabolism

2012 ◽  
Vol 108 (3) ◽  
pp. 381-392 ◽  
Author(s):  
Felino R. Cagampang ◽  
Kimberley D. Bruce
Keyword(s):  
Circadian Clock ◽  
Well Being ◽  
Internal Clock ◽  
Feedback Mechanism ◽  
Hypothalamic Region ◽  
Peripheral Tissues ◽  
Clock System ◽  
Physiological Processes ◽  
Liver And Pancreas ◽  
Molecular Components

Mammals have an endogenous timing system in the suprachiasmatic nuclei (SCN) of the hypothalamic region of the brain. This internal clock system is composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24 h (hence the term ‘circadian’). These circadian oscillations bring about rhythmic changes in downstream molecular pathways and physiological processes such as those involved in nutrition and metabolism. It is now emerging that the molecular components of the clock system are also found within the cells of peripheral tissues, including the gastrointestinal tract, liver and pancreas. The present review examines their role in regulating nutritional and metabolic processes. In turn, metabolic status and feeding cycles are able to feed back onto the circadian clock in the SCN and in peripheral tissues. This feedback mechanism maintains the integrity and temporal coordination between various components of the circadian clock system. Thus, alterations in environmental cues could disrupt normal clock function, which may have profound effects on the health and well-being of an individual.

scholarly journals Transcriptomal dissection of soybean circadian rhythmicity in two geographically, phenotypically and genetically distinct cultivars

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yanlei Yue ◽  
Ze Jiang ◽  
Enoch Sapey ◽  
Tingting Wu ◽  
Shi Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Clock ◽  
Chromosome Structure ◽  
Clock Genes ◽  
Expression Profiles ◽  
Circadian Rhythmicity ◽  
Rna Seq ◽  
Night Time ◽  
Time Points ◽  
Circadian Clock Genes

Abstract Background In soybean, some circadian clock genes have been identified as loci for maturity traits. However, the effects of these genes on soybean circadian rhythmicity and their impacts on maturity are unclear. Results We used two geographically, phenotypically and genetically distinct cultivars, conventional juvenile Zhonghuang 24 (with functional J/GmELF3a, a homolog of the circadian clock indispensable component EARLY FLOWERING 3) and long juvenile Huaxia 3 (with dysfunctional j/Gmelf3a) to dissect the soybean circadian clock with time-series transcriptomal RNA-Seq analysis of unifoliate leaves on a day scale. The results showed that several known circadian clock components, including RVE1, GI, LUX and TOC1, phase differently in soybean than in Arabidopsis, demonstrating that the soybean circadian clock is obviously different from the canonical model in Arabidopsis. In contrast to the observation that ELF3 dysfunction results in clock arrhythmia in Arabidopsis, the circadian clock is conserved in soybean regardless of the functional status of J/GmELF3a. Soybean exhibits a circadian rhythmicity in both gene expression and alternative splicing. Genes can be grouped into six clusters, C1-C6, with different expression profiles. Many more genes are grouped into the night clusters (C4-C6) than in the day cluster (C2), showing that night is essential for gene expression and regulation. Moreover, soybean chromosomes are activated with a circadian rhythmicity, indicating that high-order chromosome structure might impact circadian rhythmicity. Interestingly, night time points were clustered in one group, while day time points were separated into two groups, morning and afternoon, demonstrating that morning and afternoon are representative of different environments for soybean growth and development. However, no genes were consistently differentially expressed over different time-points, indicating that it is necessary to perform a circadian rhythmicity analysis to more thoroughly dissect the function of a gene. Moreover, the analysis of the circadian rhythmicity of the GmFT family showed that GmELF3a might phase- and amplitude-modulate the GmFT family to regulate the juvenility and maturity traits of soybean. Conclusions These results and the resultant RNA-seq data should be helpful in understanding the soybean circadian clock and elucidating the connection between the circadian clock and soybean maturity.

scholarly journals DASH-type cryptochromes – solved and open questions

2020 ◽  
Vol 401 (12) ◽  
pp. 1487-1493
Author(s):  
Stephan Kiontke ◽  
Tanja Göbel ◽  
Annika Brych ◽  
Alfred Batschauer
Keyword(s):  
Dna Repair ◽  
Circadian Clock ◽  
Blue Light ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Open Questions ◽  
Essential Components ◽  
Repair Activity ◽  
Almost All ◽  
Uv Lesions

AbstractDrosophila, Arabidopsis, Synechocystis, human (DASH)-type cryptochromes (cry-DASHs) form one subclade of the cryptochrome/photolyase family (CPF). CPF members are flavoproteins that act as DNA-repair enzymes (DNA-photolyases), or as ultraviolet(UV)-A/blue light photoreceptors (cryptochromes). In mammals, cryptochromes are essential components of the circadian clock feed-back loop. Cry-DASHs are present in almost all major taxa and were initially considered as photoreceptors. Later studies demonstrated DNA-repair activity that was, however, restricted to UV-lesions in single-stranded DNA. Very recent studies, particularly on microbial organisms, substantiated photoreceptor functions of cry-DASHs suggesting that they could be transitions between photolyases and cryptochromes.

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