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Biological clock Nuclear receptor

Martina Magni, Giacomo Buscemi, Laura Zannini
Cell cycle and apoptosis regulator 2 (CCAR2 or DBC1) is a human protein recently emerged as a novel and important player of the DNA damage response (DDR). Indeed, upon genotoxic stress, CCAR2, phosphorylated by the apical DDR kinases ATM and ATR, increases its binding to the NAD+-dependent histone deacetylase SIRT1 and inhibits SIRT1 activity. This event promotes the acetylation and activation of p53, a SIRT1 target, and the subsequent induction of p53 dependent apoptosis. In addition, CCAR2 influences DNA repair pathway choice and promotes the chromatin relaxation necessary for the repair of heterochromatic DNA lesions...
April 2018: Mutation Research
Gianluigi Mazzoccoli, Salvatore De Cosmo, Tommaso Mazza
Non-alcoholic fatty liver disease (NAFLD) is the most frequent hepatic pathology in the Western world and may evolve into steatohepatitis (NASH), increasing the risk of cirrhosis, portal hypertension and hepatocellular carcinoma. NAFLD derives from the accumulation of hepatic fat due to discrepant free fatty acid metabolism. Other factors contributing to this are deranged nutrients and bile acids fluxes as well as alterations in nuclear receptors, hormones, and intermediary metabolites, which impact on signaling pathways involved in metabolism and inflammation...
2018: Frontiers in Physiology
Sarbani Ghoshal, Joseph R Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S Leon, D C Rao, James S Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V Nuñez, Kimber L Stanhope, Deborah A Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P Weiss, Alisha R Coffey, Brian J Bennett, Praveen Sethupathy, Thomas P Burris, Peter J Havel, Andrew A Butler
OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function. METHODS: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models...
February 2018: Molecular Metabolism
S Sen, S Dumont, D Sage-Ciocca, S Reibel, P de Goede, A Kalsbeek, E Challet
The nuclear receptor REV-ERBα is part of the molecular clock mechanism and is considered to be involved in a variety of biological processes within metabolically active peripheral tissues as well. To investigate whether Rev-erbα (also known as Nr1d1) in the brain plays a role in the daily variations of energy metabolism, feeding behaviour and the sleep-wake cycle, we studied mice with global (GKO) or brain (BKO) deletion of Rev-erbα. Mice were studied both in a light/dark cycle and in constant darkness, and then 24-hour variations of Respiratory quotient (RQ) and energy expenditure, as well as the temporal patterns of rest-activity and feeding behaviour, were recorded...
January 2018: Journal of Neuroendocrinology
Takao Hirai
The clock system has been identified as one of the major mechanisms controlling cellular functions. Circadian clock gene oscillations also actively participate in the functions of various cell types including bone-related cells. Previous studies demonstrated that clock genes were expressed in bone tissue and also that their expression exhibited circadian rhythmicity. Recent findings have shown that sympathetic tone plays a central role in biological oscillations in bone. Adrenergic receptor (AR) signaling regulates the expression of clock genes in cancellous bone...
January 2018: Neurochemical Research
Salvatore De Cosmo, Gianluigi Mazzoccoli
Liver metabolic pathways are driven by the biological clock, and appropriate timing of 24-h patterns of metabolic gene expression as well as anabolic/catabolic processes with wake-related activity/feeding and sleep-related resting/fasting cycles preserves hepatic healthiness. The interplay among the liver metabolic pathways and the molecular clockwork is geared by the nuclear receptors, and ligand-dependent transcription factors that gauge the cellular nutritional status and redox balance, bind hormones and metabolites, and modulate the transcription of thousands target genes through their DNA-binding domain...
2017: Frontiers in Endocrinology
Huan Li, Wen-Kai Li, Yuan-Fu Lu, Li-Xin Wei, Jie Liu
Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and "detoxification," and is mainly composed of metacinnabar (β-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods...
2016: PeerJ
Sonal A Patel, Amol Chaudhari, Richa Gupta, Nikkhil Velingkaar, Roman V Kondratov
Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice...
April 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sophie S B Giguère, Amanda J Guise, Pierre M Jean Beltran, Preeti M Joshi, Todd M Greco, Olivia L Quach, Jeffery Kong, Ileana M Cristea
Deleted in breast cancer 1 (DBC1) has emerged as an important regulator of multiple cellular processes, ranging from gene expression to cell cycle progression. DBC1 has been linked to tumorigenesis both as an inhibitor of histone deacetylases, HDAC3 and sirtuin 1, and as a transcriptional cofactor for nuclear hormone receptors. However, despite mounting interest in DBC1, relatively little is known about the range of its interacting partners and the scope of its functions. Here, we carried out a functional proteomics-based investigation of DBC1 interactions in two relevant cell types, T cells and kidney cells...
March 2016: Molecular & Cellular Proteomics: MCP
Z Gerhart-Hines, M A Lazar
The circadian clock orchestrates the co-ordinated rhythmicity of numerous metabolic pathways to anticipate daily and seasonal changes in energy demand. This vital physiological function is controlled by a set of individual clock components that are present in each cell of the body, and regulate each other as well as clock output genes. A key factor is the nuclear receptor, Rev-erbα, a transcriptional repressor which functions not only as a clock component but also as a modulator of metabolic programming in an array of tissues...
September 2015: Diabetes, Obesity & Metabolism
Huatao Chen, Keishiro Isayama, Makoto Kumazawa, Lijia Zhao, Nobuhiko Yamauchi, Yasufumi Shigeyoshi, Seiichi Hashimoto, Masa-aki Hattori
The nuclear receptor REV-ERBα links circadian rhythms and numerous physiological processes, but its physiological role in ovaries remains largely unknown. The aim of this study was to determine the potential role of REV-ERBα in the regulation of the transcription of its putative target genes in granulosa cells (GCs) prepared from Per2-destablized luciferase (dLuc) reporter gene transgenic rats. Alas1, Ppargc1a, and Il6 were chosen as representatives for genes analysis. A real-time monitoring system of Per2 promoter activity was performed to detect Per2-dLuc circadian oscillations...
2015: Chronobiology International
Fan Wang, Yong Luo, Caiyan Li, Lvan Chen
AIMS AND BACKGROUND: Growing evidence indicates that disruption of circadian rhythms may be a risk factor for the development of glioma. However, the molecular mechanisms underlying the genetic regulation of circadian rhythms in glioma cells have yet to be explored. METHODS AND STUDY DESIGN: Using immunohistochemical staining and methylation-specific PCR techniques, we examined the expression of the period 2 (PER2) gene, one of the most important clock genes, epidermal growth factor receptor (EGFR), and proliferating cell nuclear antigen (PCNA) in 92 gliomas...
November 2014: Tumori
Bing Ji, Qing Yang, Paul G Genever, Ronald J Patton, Michael J Fagan
Bone remodelling is a vital process which enables bone to repair, renew and optimize itself. Disorders in the bone remodelling process are inevitably manifested in bone-related diseases, such as hypothyroidism, primary hyperparathyroidism and osteoporosis. In our previous work, a predator-prey based mathematical model was developed to simulate bone remodelling cycles under normal and two pathological conditions, hypothyroidism and primary hyperparathyroidism, for trabecular bone at a fixed point. However, the biochemical meanings of the model parameters were not fully explored...
October 2014: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine
José Xavier-Neto, Ângela M Sousa Costa, Ana Carolina M Figueira, Carlo Donato Caiaffa, Fabio Neves do Amaral, Lara Maldanis Cerqueira Peres, Bárbara Santos Pires da Silva, Luana Nunes Santos, Alexander R Moise, Hozana Andrade Castillo
Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling...
February 2015: Biochimica et Biophysica Acta
Carlo C Lazado, Hiruni P S Kumaratunga, Kazue Nagasawa, Igor Babiak, Christopher Marlowe A Caipang, Jorge M O Fernandes
The notion that the circadian rhythm is exclusively regulated by a central clock has been challenged by the discovery of peripheral oscillators. These peripheral clocks are known to have a direct influence on the biological processes in a tissue or cell. In fish, several peripheral clocks respond directly to light, thus raising the hypothesis of autonomous regulation. Several clock genes are expressed with daily rhythmicity in Atlantic cod (Gadus morhua) fast skeletal muscle. In the present study, myosatellite cell culture and short-term cultured fast skeletal muscle explant models were developed and characterized, in order to investigate the autonomy of the clock system in skeletal muscle of Atlantic cod...
October 2014: Molecular Biology Reports
Yukimasa Takeda, Hong Soon Kang, Johannes Freudenberg, Laura M DeGraff, Raja Jothi, Anton M Jetten
The hepatic circadian clock plays a key role in the daily regulation of glucose metabolism, but the precise molecular mechanisms that coordinate these two biological processes are not fully understood. In this study, we identify a novel connection between the regulation of RORγ by the clock machinery and the diurnal regulation of glucose metabolic networks. We demonstrate that particularly at daytime, mice deficient in RORγ exhibit improved insulin sensitivity and glucose tolerance due to reduced hepatic gluconeogenesis...
2014: PLoS Genetics
Xuan Zhao, Han Cho, Ruth T Yu, Annette R Atkins, Michael Downes, Ronald M Evans
Circadian rhythms characterize almost every aspect of human physiology, endocrinology, xenobiotic detoxification, cell growth, and behavior. Modern lifestyles that disrupt our normal circadian rhythms are increasingly thought to contribute to various disease conditions ranging from depression and metabolic disorders to cancer. This self-sustained time-keeping system is generated and maintained by an endogenous molecular machine, the circadian clock, which is a transcriptional mechanism composed of the transcription factors CLOCK and BMAL and their co-repressors, PER and CRY...
May 2014: EMBO Reports
Ron C Anafi, Yool Lee, Trey K Sato, Anand Venkataraman, Chidambaram Ramanathan, Ibrahim H Kavakli, Michael E Hughes, Julie E Baggs, Jacqueline Growe, Andrew C Liu, Junhyong Kim, John B Hogenesch
Over the last decades, researchers have characterized a set of "clock genes" that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components...
April 2014: PLoS Biology
Gianluigi Mazzoccoli, Manlio Vinciguerra, Jude Oben, Roberto Tarquini, Salvatore De Cosmo
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of triglycerides in the hepatocytes in the absence of excess alcohol intake, and is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as fatty acid storage and disposal. Liver metabolic pathways are driven by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression with the alternation of anabolic processes corresponding to feeding/activity during wake times, and catabolic processes characterizing fasting/resting during sleep...
September 2014: Liver International: Official Journal of the International Association for the Study of the Liver
Janusz K Rybakowski, Monika Dmitrzak-Weglar, Sebastian Kliwicki, Joanna Hauser
OBJECTIVES: The therapeutic action of lithium in bipolar mood disorder may be connected with its effect on biological rhythms. In the present study, an attempt was made to investigate an association between multiple single nucleotide polymorphisms (SNPs) and their haplotypes pertaining to four genes involved in regulation of biological rhythms [circadian locomotor output cycle kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like (ARNTL), timeless circadian clock (TIMELESS), period circadian clock 3 (PER 3)], and the efficacy of lithium prophylaxis...
March 2014: Bipolar Disorders
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