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https://www.readbyqxmd.com/read/28990415/redox-regulation-of-heme-oxygenase-2-and-the-transcription-factor-rev-erb-through-heme-regulatory-motifs
#1
Angela S Fleischhacker, Eric Carter, Stephen Ragsdale
SIGNIFICANCE: Heme binds to and serves as a cofactor for a myriad of proteins involved in diverse biological processes. Hemoproteins also exhibit varying modes of heme binding, suggesting that protein environment contributes to the functional versatility of this prosthetic group. The subject of this review is a subset of hemoproteins that contain at least one heme regulatory motif (HRM), which is a short sequence containing a Cys-Pro core that in many cases binds heme with the Cys acting as an axial ligand...
October 7, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28878135/rev-erb%C3%AE-ameliorates-heart-failure-through-transcription-repression
#2
Lilei Zhang, Rongli Zhang, Chih-Liang Tien, Ricky E Chan, Keiki Sugi, Chen Fu, Austin C Griffin, Yuyan Shen, Thomas P Burris, Xudong Liao, Mukesh K Jain
A cure for heart failure remains a major unmet clinical need, and current therapies targeting neurohomonal and hemodynamic regulation have limited efficacy. The pathological remodeling of the myocardium has been associated with a stereotypical gene expression program, which had long been viewed as the consequence and not the driver of the disease until very recently. Despite the advance, there is no therapy available to reverse the already committed gene program. Here, we demonstrate that transcriptional repressor REV-ERB binds near driver transcription factors across the genome...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28851928/calorie-restriction-effects-on-circadian-rhythms-in-gene-expression-are-sex-dependent
#3
Artem A Astafev, Sonal A Patel, Roman V Kondratov
The rhythms in the expression of circadian clock genes are affected by calorie restriction (CR), a dietary paradigm known to increase lifespan. Many physiological effects of CR differ between males and females; here we investigated if the sex of animals affects the CR induced changes in the circadian rhythms. The liver expression of some circadian clock genes such as Bmal1 and three Periods (Per1, Per2 and Per3) and the effect of CR on the expression of these genes were sex independent, while the expression of Rev-Erb alpha, Ror gamma and both Cryptochome (Cry1 and Cry2) genes was different between males and females...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28804711/annotation-of-the-nuclear-receptors-in-an-estuarine-fish-species-fundulus-heteroclitus
#4
William S Baldwin, W Tyler Boswell, Gautam Ginjupalli, Elizabeth J Litoff
The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28712038/binding-mode-prediction-and-md-mmpbsa-based-free-energy-ranking-for-agonists-of-rev-erb%C3%AE-ncor
#5
Yvonne Westermaier, Sergio Ruiz-Carmona, Isabelle Theret, Françoise Perron-Sierra, Guillaume Poissonnet, Catherine Dacquet, Jean A Boutin, Pierre Ducrot, Xavier Barril
The knowledge of the free energy of binding of small molecules to a macromolecular target is crucial in drug design as is the ability to predict the functional consequences of binding. We highlight how a molecular dynamics (MD)-based approach can be used to predict the free energy of small molecules, and to provide priorities for the synthesis and the validation via in vitro tests. Here, we study the dynamics and energetics of the nuclear receptor REV-ERBα with its co-repressor NCoR and 35 novel agonists. Our in silico approach combines molecular docking, molecular dynamics (MD), solvent-accessible surface area (SASA) and molecular mechanics poisson boltzmann surface area (MMPBSA) calculations...
July 15, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28702326/rev-erb-co-regulates-muscle-regeneration-via-tethered-interaction-with-the-nf-y-cistrome
#6
Ryan D Welch, Chun Guo, Monideepa Sengupta, Katherine J Carpenter, Natalie A Stephens, Stacy A Arnett, Marvin J Meyers, Lauren M Sparks, Steven R Smith, Jinsong Zhang, Thomas P Burris, Colin A Flaveny
OBJECTIVE: The loss of skeletal muscle mass and strength are a central feature of traumatic injury and degenerative myopathies. Unfortunately, pharmacological interventions typically fail to stem the long-term decline in quality of life. Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been shown to stimulate myoblast differentiation. Yet the mechanisms that allow Rev-Erb to pleiotropically inhibit muscle differentiation are not well understood. In this study, we sought to elucidate the role of Rev-Erb in the regulation of muscle differentiation and regeneration in vivo...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28674930/trojan-horse-strategy-for-non-invasive-interference-of-clock-gene-in-the-oyster-crassostrea-gigas
#7
Laura Payton, Mickael Perrigault, Jean-Paul Bourdineaud, Anjara Marcel, Jean-Charles Massabuau, Damien Tran
RNA interference is a powerful method to inhibit specific gene expression. Recently, silencing target genes by feeding has been successfully carried out in nematodes, insects, and small aquatic organisms. A non-invasive feeding-based RNA interference is reported here for the first time in a mollusk bivalve, the pacific oyster Crassostrea gigas. In this Trojan horse strategy, the unicellular alga Heterocapsa triquetra is the food supply used as a vector to feed oysters with Escherichia coli strain HT115 engineered to express the double-stranded RNA targeting gene...
August 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28625476/feedback-loops-interlocked-at-competitive-binding-sites-amplify-and-facilitate-genetic-oscillations
#8
Koichiro Uriu, Hajime Tei
Positive and negative feedback loops are often present in regulatory networks for genetic oscillations. Relative time scales and integration of these feedback loops are key to robust oscillations in expression levels. Using examples from the circadian clock and synthetic genetic oscillators, we study positive and negative feedback loops interlocked at competitive binding sites. In the mammalian circadian clock, a key clock gene Bmal1 is regulated by the activator ROR and the repressor REV-ERB. Conversely, Bmal1 activates both of them, forming interlocked feedback loops...
June 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28586319/rev-erb-and-ror-therapeutic-targets-for-treating-myopathies
#9
REVIEW
Ryan D Welch, Colin A Flaveny
Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis...
June 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28382017/disrupted-ultradian-activity-rhythms-and-differential-expression-of-several-clock-genes-in-interleukin-6-deficient-mice
#10
Francisco J Monje, Ana Cicvaric, Juan Pablo Acevedo Aguilar, Immanuel Elbau, Orsolya Horvath, Weifei Diao, Micaela Glat, Daniela D Pollak
The characteristics of the cycles of activity and rest stand out among the most intensively investigated aspects of circadian rhythmicity in humans and experimental animals. Alterations in the circadian patterns of activity and rest are strongly linked to cognitive and emotional dysfunctions in severe mental illnesses such as Alzheimer's disease (AD) and major depression (MDD). The proinflammatory cytokine interleukin 6 (IL-6) has been prominently associated with the pathogenesis of AD and MDD. However, the potential involvement of IL-6 in the modulation of the diurnal rhythms of activity and rest has not been investigated...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#11
Faisal J Alibhai, Jonathan LaMarre, Cristine J Reitz, Elena V Tsimakouridze, Jeffrey T Kroetsch, Steffen-Sebastian Bolz, Alex Shulman, Samantha Steinberg, Thomas P Burris, Gavin Y Oudit, Tami A Martino
The circadian mechanism underlies daily rhythms in cardiovascular physiology and rhythm disruption is a major risk factor for heart disease and worse outcomes. However, the role of circadian rhythms is generally clinically unappreciated. Clock is a core component of the circadian mechanism and here we examine the role of Clock as a vital determinant of cardiac physiology and pathophysiology in aging. Clock(Δ19/Δ19) mice develop age-dependent increases in heart weight, hypertrophy, dilation, impaired contractility, and reduced myogenic responsiveness...
April 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28213272/rev-erb-regulation-of-cholesterologenesis
#12
Sadichha Sitaula, Jinsong Zhang, Fernanda Ruiz, Thomas P Burris
REV-ERBα and REV-ERBβ are heme regulated nuclear receptors that are known to regulate metabolic pathways. We previously demonstrated that treatment of mice with synthetic REV-ERB agonists suppressed plasma cholesterol levels and the hepatic levels of the rate limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-CoA reductase). Here, we characterize the role of REV-ERB on the cholesterol biosynthetic pathway in greater detail. The REV-ERB agonist SR9009 reduced plasma cholesterol levels in both wild type C57Bl/6 and low density lipoprotein receptor (LDLR) null mice as well as reducing the expression of an array of genes within the cholesterol biosynthetic pathway...
May 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28072861/identification-of-the-molecular-clockwork-of-the-oyster-crassostrea-gigas
#13
Mickael Perrigault, Damien Tran
Molecular clock system constitutes the origin of biological rhythms that allow organisms to anticipate cyclic environmental changes and adapt their behavior and physiology. Components of the molecular clock are largely conserved across a broad range of species but appreciable diversity in clock structure and function is also present especially in invertebrates. The present work aimed at identify and characterize molecular clockwork components in relationship with the monitoring of valve activity behavior in the oyster Crassostrea gigas...
2017: PloS One
https://www.readbyqxmd.com/read/27995168/data-on-the-effect-of-pro-fibrotic-cytokine-tgf-%C3%AE-on-hepatic-stellate-cell-autophagy
#14
Paul G Thomes, Elizabeth Brandon-Warner, Ting Li, Terrence M Donohue, Laura W Schrum
Our data describe autophagic flux in primary rat hepatic stellate cells (rHSCs) treated with pro-fibrotic growth factor, transforming growth factor beta (TGF-β). An autophagy flux experiment determines the rate of synthesis and degradation of the autophagosome marker, LC3-II in the presence and absence of the lysosomal inhibitor bafilomcyin, which blocks LC3-II degradation in lysosomes. The effects of a test agent on LC3-II flux through the autophagic pathway is determined immunochemically by its relative amounts detected in lysates of cells treated with and without bafilomycin...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/27988807/effects-of-bright-light-exposure-during-daytime-on-peripheral-clock-gene-expression-in-humans
#15
Maki Sato, Tomoko Wakamura, Takeshi Morita, Akihiko Okamoto, Makoto Akashi, Takuya Matsui, Motohiko Sato
Light is the strongest synchronizer controlling circadian rhythms. The intensity and duration of light change throughout the year, thereby influencing body weight, food preferences, and melatonin secretion in humans and animals. Although the expression of clock genes has been examined using human samples, it currently remains unknown whether bright light during the daytime affects the expression of these genes in humans. Therefore, we herein investigated the effects of bright light exposure during the daytime on clock gene expression in the hair follicular and root cells of the human scalp...
June 2017: International Journal of Biometeorology
https://www.readbyqxmd.com/read/27893989/drug-discovery-targeting-heme-based-sensors-and-their-coupled-activities
#16
REVIEW
Eduardo Henrique Silva Sousa, Luiz Gonzaga de França Lopes, Gonzalo Gonzalez, Marie-Alda Gilles-Gonzalez
Heme-based sensors have emerged during the last 20years as being a large family of proteins that occur in all kingdoms of life. A myriad of biological adaptations are associated with these sensors, which include vasodilation, bacterial virulence, dormancy, chemotaxis, biofilm formation, among others. Due to the key activities regulated by these proteins along with many other systems that use similar output domains, there is a growing interest in developing small molecules as their regulators. Here, we review the development of potential activators and inhibitors for many of these systems, including human soluble guanylate cyclase, c-di-GMP-related enzymes, Mycobacterium tuberculosis DevR/DevS/DosT (differentially expressed in virulent strain response regulator/sensor/dormancysurvival sensorT), the Rev-erb-α and β nuclear receptor, among others...
February 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27760313/a-mathematical-model-of-the-liver-circadian-clock-linking-feeding-and-fasting-cycles-to-clock-function
#17
Aurore Woller, Hélène Duez, Bart Staels, Marc Lefranc
To maintain energy homeostasis despite variable energy supply and consumption along the diurnal cycle, the liver relies on a circadian clock synchronized to food timing. Perturbed feeding and fasting cycles have been associated with clock disruption and metabolic diseases; however, the mechanisms are unclear. To address this question, we have constructed a mathematical model of the mammalian circadian clock, incorporating the metabolic sensors SIRT1 and AMPK. The clock response to various temporal patterns of AMPK activation was simulated numerically, mimicking the effects of a normal diet, fasting, and a high-fat diet...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27726182/the-intrinsic-microglial-clock-system-regulates-interleukin-6-expression
#18
Ryota Nakazato, Shogo Hotta, Daisuke Yamada, Miki Kou, Saki Nakamura, Yoshifumi Takahata, Hajime Tei, Rika Numano, Akiko Hida, Shigeki Shimba, Michihiro Mieda, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin-6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses. We previously demonstrated that gliotransmitter ATP induces transient expression of the clock gene Period1 via P2X7 purinergic receptors in cultured microglia. In this study, we further investigated mechanisms underlying the regulation of pro-inflammatory cytokine production by clock molecules in microglial cells...
October 11, 2016: Glia
https://www.readbyqxmd.com/read/27706103/in-vitro-metabolic-studies-of-rev-erb-agonists-sr9009-and-sr9011
#19
Lore Geldof, Koen Deventer, Kris Roels, Eva Tudela, Peter Van Eeno
SR9009 and SR9011 are attractive as performance-enhancing substances due to their REV-ERB agonist effects and thus circadian rhythm modulation activity. Although no pharmaceutical preparations are available yet, illicit use of SR9009 and SR9011 for doping purposes can be anticipated, especially since SR9009 is marketed in illicit products. Therefore, the aim was to identify potential diagnostic metabolites via in vitro metabolic studies to ensure effective (doping) control. The presence of SR9009 could be demonstrated in a black market product purchased over the Internet...
October 3, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27603791/pharmacological-targeting-the-rev-erbs-in-sleep-wake-regulation
#20
Ariadna Amador, Salvador Huitron-Resendiz, Amanda J Roberts, Theodore M Kamenecka, Laura A Solt, Thomas P Burris
The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands...
2016: PloS One
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