scholarly journals BMAL1 but not CLOCK is associated with monochromatic green light-induced circadian rhythm of melatonin in chick pinealocytes

2019 ◽  
Vol 8 (1) ◽  
pp. 57-68 ◽  
Author(s):  
Shuhui Ma ◽  
Zixu Wang ◽  
Jing Cao ◽  
Yulan Dong ◽  
Yaoxing Chen
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Clock Genes ◽  
Critical Role ◽  
Green Light ◽  
Circadian Oscillator ◽  
Melatonin Secretion ◽  
Expression Levels

The avian pineal gland, an independent circadian oscillator, receives external photic cues and translates them for the rhythmical synthesis of melatonin. Our previous study found that monochromatic green light could increase the secretion of melatonin and expression of CLOCK and BMAL1 in chick pinealocytes. This study further investigated the role of BMAL1 and CLOCK in monochromatic green light-induced melatonin secretion in chick pinealocytes using siRNAs interference and overexpression techniques. The results showed that si-BMAL1 destroyed the circadian rhythms of AANAT and melatonin, along with the disruption of the expression of all the seven clock genes, except CRY1. Furthermore, overexpression of BMAL1 also disturbed the circadian rhythms of AANAT and melatonin, in addition to causing arrhythmic expression of BMAL1 and CRY1/2, but had no effect on the circadian rhythms of CLOCK, BMAL2 and PER2/3. The knockdown or overexpression of CLOCK had no impact on the circadian rhythms of AANAT, melatonin, BMAL1 and PER2, but it significantly deregulated the circadian rhythms of CLOCK, BMAL2, CRY1/2 and PER3. These results suggested that BMAL1 rather than CLOCK plays a critical role in the regulation of monochromatic green light-induced melatonin rhythm synthesis in chicken pinealocytes. Moreover, both knockdown and overexpression of BMAL1 could change the expression levels of CRY2, it indicated CRY2 may be involved in the BMAL1 pathway by modulating the circadian rhythms of AANAT and melatonin.

scholarly journals Circadian Rhythm: Potential Therapeutic Target for Atherosclerosis and Thrombosis

2021 ◽  
Vol 22 (2) ◽  
pp. 676
Author(s):  
Andy W. C. Man ◽  
Huige Li ◽  
Ning Xia
Keyword(s):  
Circadian Rhythm ◽  
Cardiovascular Diseases ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Therapeutic Target ◽  
Environmental Changes ◽  
Clock Genes ◽  
Vascular System ◽  
Peripheral Tissues ◽  
Inflammatory Processes

Every organism has an intrinsic biological rhythm that orchestrates biological processes in adjusting to daily environmental changes. Circadian rhythms are maintained by networks of molecular clocks throughout the core and peripheral tissues, including immune cells, blood vessels, and perivascular adipose tissues. Recent findings have suggested strong correlations between the circadian clock and cardiovascular diseases. Desynchronization between the circadian rhythm and body metabolism contributes to the development of cardiovascular diseases including arteriosclerosis and thrombosis. Circadian rhythms are involved in controlling inflammatory processes and metabolisms, which can influence the pathology of arteriosclerosis and thrombosis. Circadian clock genes are critical in maintaining the robust relationship between diurnal variation and the cardiovascular system. The circadian machinery in the vascular system may be a novel therapeutic target for the prevention and treatment of cardiovascular diseases. The research on circadian rhythms in cardiovascular diseases is still progressing. In this review, we briefly summarize recent studies on circadian rhythms and cardiovascular homeostasis, focusing on the circadian control of inflammatory processes and metabolisms. Based on the recent findings, we discuss the potential target molecules for future therapeutic strategies against cardiovascular diseases by targeting the circadian clock.

scholarly journals Modulatory Effects of Circadian Rhythms in the Lung Adenocarcinoma Tumor Microenvironment

2021 ◽  
Author(s):  
Qianzhun Huang ◽  
Xiaoyang Su ◽  
Ning Fang ◽  
Jian Huang
Keyword(s):  
Tumor Microenvironment ◽  
Circadian Rhythms ◽  
Lung Adenocarcinoma ◽  
Circadian Clock ◽  
Drug Sensitivity ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Functional Enrichment ◽  
Expression Levels ◽  
Circadian Clock Genes

Abstract Background: Dysregulated circadian dynamic balance is strongly associated with cancer development. However, biological functions of circadian rhythms in lung adenocarcinoma (LUAD) have not been elucidated. This study aimed at valuating the modulatory effects of circadian rhythms in the LUAD tumor microenvironment.Methods: Multiple open-source bioinformatics research platforms are used to comprehensively elucidate the expression level, prognosis, potential biological function, drug sensitivity, and immune microenvironment of circadian clock genes in LUAD.Results: Most circadian clock genes in LUAD are dysregulated and are strongly correlated with patient prognosis, and missense mutations at splicing sites of these genes. Besides, these genes are closely associated with some well-known cancer-related marker pathways, which are mainly involved in the inhibition of the Apoptosis, Cell cycle, and DNA Damage Response Pathway. Furthermore, functional enrichment analysis revealedthat circadian clock genes regulate transcription factor activities and circadian rhythms in LUAD tissues. As for drug sensitivity, high expression of CLOCK, CRY1, and NR1D2 as well as suppressedPER2 and CRY2 expression levels are associated with drug resistance. The expression levels of circadian clock genes in LUAD correlate with immune infiltration and are involved in the regulation of immunosuppression.Conclusions: Our multi-omics analysis provides a more comprehensive understanding of the molecular mechanisms of the circadian clock genes in LUAD and provides new insights for a more precise screening of prognostic biomarkers and immunotherapy.

scholarly journals Chronic Corticosterone Disrupts the Circadian Rhythm of CRH Expression and M6a RNA Methylation in the Chicken Hypothalamus

2021 ◽  
Author(s):  
Yang Yang ◽  
Wanwan Han ◽  
Aijia Zhang ◽  
Mindie Zhao ◽  
Wei Cong ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Chronic Stress ◽  
Hpa Axis ◽  
Clock Genes ◽  
Diurnal Fluctuation ◽  
Opposite Pattern ◽  
Rna Methylation ◽  
Diurnal Patterns ◽  
M6a Rna Methylation

Abstract Corticotropin-releasing hormone (CRH), the major secretagogue of the hypothalamic-pituitary-adrenal (HPA) axis, is intricately intertwined with the clock genes to regulate the circadian rhythm of various body functions. N6-methyladenosine (m6A) RNA methylation is involved in the regulation of circadian rhythm, yet it remains unknown whether CRH expression and m6A modification oscillate with the clock genes in chicken hypothalamus and how the circadian rhythms change under chronic stress. Here, we show that chronic exposure to corticosterone (CORT) eliminated the diurnal patterns of plasma CORT and melatonin levels in the chicken. The circadian rhythms of clock genes in hippocampus, hypothalamus and pituitary are all disturbed to different extent in CORT-treated chickens. The most striking changes occur in hypothalamus in which the diurnal fluctuation of CRH mRNA is flattened, together with mRNA of other feeding-related neuropeptides. Interestingly, hypothalamic m6A level oscillates in an opposite pattern to CRH mRNA, with lowest m6A level after midnight (ZT18) corresponding to the peak of CRH mRNA before dawn (ZT22). CORT diminished the circadian rhythm of m6A methylation with significantly increased level at night. Further site-specific m6A analysis on 3’UTR of CRH mRNA indicates that higher m6A on 3’UTR of CRH mRNA coincides with lower CRH mRNA at night (ZT18 and ZT22). Our results indicate that chronic stress disrupts the circadian rhythms of CRH expression in hypothalamus, leading to dysfunction of HPA axis in the chicken. RNA m6A modification is involved in the regulation of circadian rhythms in chicken hypothalamus under both basal and chronic stress conditions.

Abstract P160: Non-invasive Method to Assess Human Circadian Rhythms

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Daian Chen ◽  
S Justin Thomas ◽  
David A Calhoun ◽  
David M Pollock ◽  
Jennifer S Pollock
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Salivary Cortisol ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Light Exposure ◽  
Rna Isolation ◽  
Buccal Cells ◽  
Non Invasive ◽  
Salivary Melatonin

Circadian rhythms are controlled by an endogenous time-keeping system oscillating approximately on a 24-h cycle under constant conditions. These rhythms depend on a network of interacting genes and proteins, including transcriptional activators such as CLOCK, NPAS2, and ARNTL (BMAL1), which induce transcription of the clock genes Period ( Per1 , Per2 , and Per3 ) and Cryptochrome ( Cry1 and Cry2 ). Human salivary cortisol and melatonin follow a clear circadian rhythm as well. Disruption of the circadian rhythm and sleep-wake cycles are considered risk factors for a variety of health problems, especially hypertension and other cardiovascular and metabolic diseases. Here we put together practical methods for assessing circadian rhythms in adult subjects conducted by each individual. This method is non-invasive, inexpensive and provides a predictive profile of an individual’s circadian rhythm related to clock-controlled gene expression in buccal cells, salivary cortisol, salivary melatonin, and subject’s activity or sleep. Subjects are instructed on how to obtain buccal cells using swabs (Whatman OmniSwab) from the inside of their cheeks and collect saliva using salivettes (Sarstedt) every 4 hours starting at 6am, for 2 consecutive days. Subjects also wear actigraphy watches (Phillips Respironics) during the 2 days, to record their activity, light exposure and estimates of sleep times. To monitor adherence to correct time point collections, each subject is given an electronic vial called eCAP (Information Mediary Corp) that records the exact time the container is opened to place samples once collected. We demonstrate feasibility to extract up to 150ng/μl of RNA (Ambion RNAqueous-Micro Total RNA Isolation Kit) from buccal cells swabs. Salivary melatonin and cortisol are measured by radioimmunoassay (Buhlmann Lab) with melatonin peak levels ranging from 14 to 23 pg/ml and cortisol peak levels ranging from 10 to 24 ng/ml. We suggest that buccal cell expression of clock-controlled genes, salivary melatonin, salivary cortisol, and actigraphy data are valuable in providing reliable assessment of human circadian rhythm profiles under a variety of conditions.

scholarly journals Role and Therapeutic Potential of Melatonin in the Central Nervous System and Cancers

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1567
Author(s):  
Sangiliyandi Gurunathan ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Dark Phase ◽  
Anti Inflammatory ◽  
The Impact

Melatonin (MLT) is a powerful chronobiotic hormone that controls a multitude of circadian rhythms at several levels and, in recent times, has garnered considerable attention both from academia and industry. In several studies, MLT has been discussed as a potent neuroprotectant, anti-apoptotic, anti-inflammatory, and antioxidative agent with no serious undesired side effects. These characteristics raise hopes that it could be used in humans for central nervous system (CNS)-related disorders. MLT is mainly secreted in the mammalian pineal gland during the dark phase, and it is associated with circadian rhythms. However, the production of MLT is not only restricted to the pineal gland; it also occurs in the retina, Harderian glands, gut, ovary, testes, bone marrow, and lens. Although most studies are limited to investigating the role of MLT in the CNS and related disorders, we explored a considerable amount of the existing literature. The objectives of this comprehensive review were to evaluate the impact of MLT on the CNS from the published literature, specifically to address the biological functions and potential mechanism of action of MLT in the CNS. We document the effectiveness of MLT in various animal models of brain injury and its curative effects in humans. Furthermore, this review discusses the synthesis, biology, function, and role of MLT in brain damage, and as a neuroprotective, antioxidative, anti-inflammatory, and anticancer agent through a collection of experimental evidence. Finally, it focuses on the effect of MLT on several neurological diseases, particularly CNS-related injuries.

scholarly journals Increase in 6-Hydroxymelatonin Excretion in Humans during Ascent to High Altitudes

2004 ◽  
Vol 89 (9) ◽  
pp. 4388-4390 ◽  
Author(s):  
Herwig Frisch ◽  
Franz Waldhauser ◽  
Thomas Waldhör ◽  
Andrea Müllner-Eidenböck ◽  
Pritam Neupane ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Pineal Gland ◽  
Diurnal Variation ◽  
Healthy Volunteers ◽  
High Altitude ◽  
Physiological Role ◽  
Physiological Significance ◽  
High Altitudes ◽  
Lower Altitude

Melatonin (MLT), the pineal gland hormone involved in the regulation of circadian rhythms, shows characteristic diurnal variation. Its physiological role in humans is not clear. Exposure to high altitudes may disrupt the circadian rhythm and lead to various endocrine changes. MLT in humans has not been studied under these conditions. Urinary 6-hydroxy-MLT sulfate (aMT6s) excretion was analyzed during the day (0700–2200 h) and night (2200–0700 h) phases. A cohort of 33 healthy volunteers, aged 19–65 yr, was studied during an ascent to a high altitude in the Himalayas on three occasions (at a lower altitude, at 3400 m, and after reaching maximal altitudes of 5600–6100 m). aMT6s excretion during the daytime remained unchanged during exposure to high altitudes. As expected, nocturnal values were higher than diurnal values at each point in time. However, there was a significant increase in nocturnal MLT excretion after the ascent to high altitudes. Ascent to high altitudes is associated with increased nocturnal excretion of aMT6s. The mechanism and physiological significance of this MLT increase are unclear.

Enhanced effect of daytime restricted feeding on the circadian rhythm of streptozotocin-induced type 2 diabetic rats

2012 ◽  
Vol 302 (9) ◽  
pp. E1027-E1035 ◽  
Author(s):  
Tao Wu ◽  
Fen ZhuGe ◽  
Lu Sun ◽  
Yinhua Ni ◽  
Ou Fu ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Pineal Gland ◽  
Circadian Clock ◽  
Clock Genes ◽  
Activity Rhythm ◽  
Diabetic Rats ◽  
Restricted Feeding ◽  
Behavioral Rhythm ◽  
Type 2 Diabetic

There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock by type 2 diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we examined not only the expression of circadian genes in the heart and pineal gland but also the behavioral rhythm of type 2 diabetic and control rats in both the nighttime restricted feeding (NRF) and daytime restricted feeding (DRF) conditions. In the NRF condition, the circadian expression of clock genes in the heart and pineal gland was conserved in the diabetic rats, being similar to that in the control rats. DRF shifted the circadian phases of peripheral clock genes more efficiently in the diabetic rats than those in the control rats. Moreover, the activity rhythm of rats in the diabetic group was completely shifted from the dark phase to the light phase after 5 days of DRF treatment, whereas the activity rhythm of rats in the control group was still under the control of the suprachiasmatic nucleus (SCN) after the same DRF treatment. Furthermore, the serum glucose rhythm of type 2 diabetic rats was also shifted and controlled by the external feeding schedule, ignoring the SCN rhythm. Therefore, DRF shows stronger effect on the reentrainment of circadian rhythm in the type 2 diabetic rats, suggesting that the circadian system in diabetes is unstable and more easily shifted by feeding stimuli.

scholarly journals Association of Expression Levels of Clock Genes and Autophagy-Related Genes under Abnormal Light/Dark Cycle Stimulation in NAFLD Mice

2020 ◽  
Author(s):  
Zhu Zhu ◽  
Zhengyang Wang ◽  
Bo Qin ◽  
Songfeng Zhao ◽  
Huafei Wang ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Sleep Disorder ◽  
High Fat Diet ◽  
Clock Genes ◽  
Lipid Deposition ◽  
High Fat ◽  
Dark Cycle ◽  
Alcoholic Fatty Liver ◽  
Expression Levels ◽  
Circadian Rhythm Sleep Disorder

Abstract Background: Environmental disorders of the circadian rhythms can lead to metabolism-related diseases or exacerbate pathological conditions. Non-alcoholic fatty liver disease (NAFLD) has emerged with a growing occurrence. In the present study, we attempted to indicate whether circadian clock may influence lipid deposition and the expression levels of autophagy-related genes in liver of mice. Methods: High-fat diet and abnormal light/dark cycles were employed to induce a mouse model of NAFLD with circadian rhythm sleep disorder. Herein, liver samples were obtained at ZT0, ZT4, ZT8, ZT12, ZT16, and ZT20 time-point to detect the rhythmic expressions of circadian genes, autophagy-related genes, and Rev-erbα. Results: Abnormal exposure to light aggravated lipid deposition in liver of mice and exacerbated disorders related to 24-h expression levels of clock genes, autophagy-related genes, and Rev-erbα. Besides, Rev-erbα could transcriptionally control the expression levels of autophagy-related genes. Conclusions: The long-term high-fat diet combined with abnormal light/dark cycle stimulation aggravated the development of NAFLD and disturbed the expressions levels of autophagy-related genes. An abnormal circadian expression may lead to NAFLD aggression. Besides, the abnormal expression levels of clock genes may create an association between circadian rhythm sleep disorder and autophagy.

scholarly journals Circ_0038467 is Overexpressed in Osteoarthritis and it Promotes the Maturation of miR-203 to Increase the Apoptosis of Chondrocytes Induced by LPS

2021 ◽  
Author(s):  
Zhongkun Gou ◽  
Quanling Wu ◽  
Changqing Jiang ◽  
Wei Dong
Keyword(s):  
Cell Apoptosis ◽  
Critical Role ◽  
Expression Levels ◽  
Apoptosis Assay ◽  
Lps Treatment

Abstract Introduction: LPS-induced inflammation contributes to osteoarthritis (OA). It is known that Circ_0038467 plays a critical role in LPS-mediated inflammation, suggesting the its involvement in OA. This study aimed to study the possible involvement of Circ_0038467 in OA.Materials and Methods: Circ_0038467, mature miR-203 and miR-203 precursor expression in controls and OA patients was determined by RT-qPCR. Circ_0038467 overexpression in chondrocytes and RT-qPCR was performed to analyze its effects on the expression of mature miR-203 and miR-203 precursor. The role of Circ_0038467 and miR-203 in cell apoptosis was analyzed by cell apoptosis assay.Results: Circ_0038467 was upregulated in OA and positively correlated with mature miR-203, but not miR-203 precursor. In chondrocytes, increased expression of both Circ_0038467 and miR-203 was observed after LPS treatment. In chondrocytes, Circ_0038467 overexpression increased the expression levels of mature miR-203, but not miR-203 precursor. Analysis of cell apoptosis showed that overexpression of Circ_0038467 and miR-203 increased cell apoptosis. In addition, miR-203 inhibitor reversed the effects of Circ_0038467 overexpression on cell apoptosis.Conclusions: Circ_0038467 is highly expressed in OA and may promote the production of mature miR-203 to increase the apoptosis of chondrocytes induced by LPS.

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