scholarly journals Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines

2021 ◽  
Vol 22 (3) ◽  
pp. 1307
Author(s):  
Akihiko Sakamoto ◽  
Yusuke Terui ◽  
Takeshi Uemura ◽  
Kazuei Igarashi ◽  
Keiko Kashiwagi
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Translational Regulation ◽  
Fluorescent Protein ◽  
Clock Genes ◽  
Nih3t3 Cells ◽  
Genes Encoding ◽  
Circadian Clock Genes ◽  
Specific Proteins ◽  
Green Fluorescent

Polyamines stimulate the synthesis of specific proteins at the level of translation, and the genes encoding these proteins are termed as the “polyamine modulon”. The circadian clock generates daily rhythms in mammalian physiology and behavior. We investigated the role of polyamines in the circadian rhythm using control and polyamine-reduced NIH3T3 cells. The intracellular polyamines exhibited a rhythm with a period of about 24 h. In the polyamine-reduced NIH3T3 cells, the circadian period of circadian clock genes was lengthened and the synthesis of BMAL1 and REV-ERBα was significantly reduced at the translation level. Thus, the mechanism of polyamine stimulation of these protein syntheses was analyzed using NIH3T3 cells transiently transfected with genes encoding enhanced green fluorescent protein (EGFP) fusion mRNA with normal or mutated 5′-untranslated region (5′-UTR) of Bmal1 or Rev-erbα mRNA. It was found that polyamines stimulated BMAL1 and REV-ERBα synthesis through the enhancement of ribosomal shunting during the ribosome shunting within the 5′-UTR of mRNAs. Accordingly, the genes encoding Bmal1 and Rev-erbα were identified as the members of “polyamine modulon”, and these two proteins are significantly involved in the circadian rhythm control.

Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian clock genes: A possible mechanism of chemotherapy-induced circadian rhythm disturbances

2008 ◽  
Vol 75 (8) ◽  
pp. 1616-1622 ◽  
Author(s):  
Hideyuki Terazono ◽  
Ahmed Hamdan ◽  
Naoya Matsunaga ◽  
Naoto Hayasaka ◽  
Hiroaki Kaji ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Genes ◽  
Rhythmic Expression ◽  
Circadian Clock Genes

scholarly journals Aging attenuates the ovarian circadian rhythm

2020 ◽  
Author(s):  
Ziru Jiang ◽  
Kexin Zou ◽  
Xia Liu ◽  
Hangchao Gu ◽  
Yicong Meng ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Granulosa Cells ◽  
Clock Genes ◽  
University Hospital ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Circadian Clock Genes ◽  
Young Mice

Abstract Objective To study the effect of aging on ovarian circadian rhythm. Design Human and animal study. Setting University hospital and research laboratory. Patients/animals Human granulosa cells were obtained by follicular aspiration from women undergoing in vitro fertilization (IVF), and ovarian and liver tissues were obtained from female C57BL/6 mice. Intervention(s) None. Main outcome measure(s) Expression of circadian genes in young and older human granulosa cells and circadian rhythm in ovaries and livers of young and older mice. Result(s) All examined circadian clock genes in human granulosa cells showed a downward trend in expression with aging, and their mRNA expression levels were negatively correlated with age (P < 0.05). Older patients (≥ 40 years of age) had significantly reduced serum anti-Müllerian hormone (AMH) levels. Except for Rev-erbα, all other examined circadian clock genes were positively correlated with the level of AMH (P < 0.05). The circadian rhythm in the ovaries of older mice (8 months) was changed significantly relative to that in ovaries of young mice (12 weeks), although the circadian rhythm in the livers of older mice was basically consistent with that of young mice. Conclusion(s) Lower ovarian reserve in older women is partially due to ovarian circadian dysrhythmia as a result of aging.

scholarly journals The role of circadian clock genes in mental disorders

2007 ◽  
Vol 9 (3) ◽  
pp. 333-342 ◽  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Psychiatric Disorders ◽  
Rem Sleep ◽  
Seasonal Affective Disorder ◽  
Clock Genes ◽  
Sleep Latency ◽  
Sleep Efficiency ◽  
Circadian Clock Genes

The study of molecular clock mechanisms in psychiatric disorders is gaining significant interest due to data suggesting that a misalignment between the endogenous circadian system and the sleep-wake cycle might contribute to the clinical status of patients suffering from a variety of psychiatric disorders. Sleep disturbances in major depressive disorder (MDD) are characterized by increased sleep latency, poorer sleep efficiency reduced latency to the first rapid eye movement (REM) sleep episode, and early-morning awakening, but there is little data to indicate a role of circadian clock genes in MDD. There is also relatively little information regarding the role of clock genes in anxiety. In contrast, a significant amount of evidence gathered in bipolar disorder (BPD) patients suggests a circadian rhythm disorder, namely an advanced circadian rhythm and state-dependent alterations of REM sleep latency. Most research on the role of clock genes in BPD has focused on polymorphisms of CLOCK, but the lithium target GSK3 may also play a significant role. A circadian phase shift is also theorized to contribute to the pathophysiology of winter seasonal affective disorder (SAD). Certain allelic combinations of NPAS2, PER3, and BMAL1 appear to contribute to the risk of SAD. In chronic schizophrenia, disturbances of sleep including insomnia and reduced sleep efficiency have been observed. Genetic studies have found associations with CLOCK, PER1, PER3, and TIMELESS. Sleep and circadian changes associated with dementia due to Alzheimer's disease suggest a functional change in the circadian master clock, which is supported by postmortem studies of clock gene expression in the brain.

scholarly journals Crosstalk between Flavonoids and the Plant Circadian Clock

2021 ◽  
Author(s):  
Sherry B. Hildreth ◽  
Evan S. Littleton ◽  
Leor C. Clark ◽  
Gabrielle C. Puller ◽  
Shihoko Kojima ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Null Allele ◽  
Clock Genes ◽  
Rna Seq ◽  
Wild Type ◽  
Specialized Metabolites ◽  
Genes Encoding ◽  
Circadian Clock Genes ◽  
Central Clock ◽  
Line Analysis

Flavonoids are a well-known class of specialized metabolites that play key roles in plant development, reproduction, and survival. Flavonoids are also of considerable interest from the perspective of human health, both as phytonutrients and pharmaceuticals. RNA-Seq analysis of an Arabidopsis null allele for chalcone synthase (CHS), which catalyzes the first step in flavonoid biosynthesis, has uncovered evidence that these compounds influence the expression of circadian clock genes in plants. Analysis of promoter-luciferase constructs showed that the transcriptional activity of genes encoding two components of the central clock, CCA1 and TOC1, across the day/night cycle is altered in CHS-deficient seedlings. The effect of flavonoids on circadian function was furthermore reflected in photosynthetic activity, with chlorophyll cycling abolished in the mutant line. Analysis of a mutant lacking flavonoid 3'-hydroxylase (F3'H) activity, and thus able to synthesize mono- but not di-hydroxylated B-ring flavonoids, suggests that the latter are at least partially responsible, as further supported by the effects of quercetin on CCA1 promoter activity in wild-type seedlings. Collectively, these experiments point to a previously-unknown connection between flavonoids and circadian cycling in plants and open the way to better understanding of the molecular basis of flavonoid action.

scholarly journals Circadian Clock, Time-Restricted Feeding and Reproduction

2020 ◽  
Vol 21 (3) ◽  
pp. 831 ◽  
Author(s):  
Xiaoyue Pan ◽  
Meredith J. Taylor ◽  
Emma Cohen ◽  
Nazeeh Hanna ◽  
Samantha Mota
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Sleep Disorder ◽  
Clock Genes ◽  
Restricted Feeding ◽  
Clock Time ◽  
Reproductive Process ◽  
Circadian Clock Genes ◽  
Research Findings ◽  
Reproductive Processes

The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

scholarly journals Ghrelin Restores the Disruption of the Circadian Clock in Steatotic Liver

2018 ◽  
Vol 19 (10) ◽  
pp. 3134 ◽  
Author(s):  
Qin Wang ◽  
Yue Yin ◽  
Weizhen Zhang
Keyword(s):  
Circadian Rhythm ◽  
Circadian Clock ◽  
Clock Gene ◽  
Clock Genes ◽  
Obese Mice ◽  
Cultured Hepatocytes ◽  
Steatotic Liver ◽  
Protein Levels ◽  
Feeding Cycle ◽  
Circadian Clock Genes

Obese mice demonstrate disruption of the circadian clock and feeding cycle. Circulating ghrelin, a hormone secreted mainly by gastric X/Alike cells, is significantly reduced in obese humans and animals. Here, we examined whether ghrelin improves the disruption of the circadian rhythm in steatotic hepatocytes and liver. The effects of ghrelin on hepatic circadian clock genes were studied in steatotic hepatocytes and liver of mice fed a high-fat diet (HFD) for 12 weeks. The circadian clock of cultured hepatocytes was synchronized by treatment with 100 nM dexamethasone for 1 h. Ghrelin was administrated to the cultured hepatocytes (10−8 M) or to mice at a dose of 11 nmol/kg/d for two weeks via a subcutaneous minipump. The mRNA and protein levels of core clock genes were analyzed. Steatosis significantly blunted the circadian pattern of clock genes such as Bmal1, Clock, and Per in cultured hepatocytes and liver. Treatment with ghrelin markedly restored the daily rhythm of the clock genes, with a robust oscillation between peak and trough in cultured hepatocytes isolated from obese mice. It also increased the abundance and expression amplitude of clock genes in steatotic liver, causing the peak of Clock to shift to the dark period and the peak of Per2 to shift to the light period compared with the control groups. Deletion of GHSR1a further deteriorated the derangement of clock gene patterns in obese mice. Ghrelin significantly increased the oscillations of mTOR/S6 signaling. We demonstrate that ghrelin restored the derangement of the circadian rhythm in steatotic liver via mTOR signaling.

scholarly journals PTBP1 Positively Regulates the Translation of Circadian Clock Gene, Period1

2020 ◽  
Vol 21 (18) ◽  
pp. 6921
Author(s):  
Wanil Kim ◽  
Jae-Cheon Shin ◽  
Kyung-Ha Lee ◽  
Kyong-Tai Kim
Keyword(s):  
Circadian Clock ◽  
Translational Regulation ◽  
Clock Gene ◽  
Clock Genes ◽  
Internal Ribosomal Entry Site ◽  
Feedback Regulation ◽  
Entry Site ◽  
Negative Feedback Regulation ◽  
Polypyrimidine Tract Binding Protein ◽  
Circadian Clock Genes

Circadian oscillations of mRNAs and proteins are the main features of circadian clock genes. Among them, Period1 (Per1) is a key component in negative-feedback regulation, which shows a robust diurnal oscillation and the importance of circadian rhythm and translational regulation of circadian clock genes has been recognized. In the present study, we investigated the 5′-untranslated region (5′-UTR) of the mouse core clock gene, Per1, at the posttranscriptional level, particularly its translational regulation. The 5′-UTR of Per1 was found to promote its translation via an internal ribosomal entry site (IRES). We found that polypyrimidine tract-binding protein 1 (PTBP1) binds to the 5′-UTR of Per1 and positively regulates the IRES-mediated translation of Per1 without affecting the levels of Per1 mRNA. The reduction of PTBP1 level also decreased the endogenous levels of the PER1 protein but not of its mRNA. As for the oscillation of PER1 expression, the disruption of PTBP1 levels lowered the PER1 expression but not the phase of the oscillation. PTBP1 also changed the amplitudes of the mRNAs of other circadian clock genes, such as Cryptochrome 1 (Cry1) and Per3. Our results suggest that the PTBP1 is important for rhythmic translation of Per1 and it fine-tunes the overall circadian system.

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