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https://www.readbyqxmd.com/read/29474860/pharmacological-targeting-of-the-mammalian-clock-reveals-a-novel-analgesic-for-osteoarthritis-induced-pain
#1
Vaskar Das, Ranjan Kc, Xin Li, Disha Varma, Sujun Qiu, Jeffrey S Kroin, Christopher B Forsyth, Ali Keshavarzian, Andre J van Wijnen, Thomas J Park, Gary S Stein, Insug O-Sullivan, Thomas P Burris, Hee-Jeong Im
Environmental disruption of the circadian rhythm is linked with increased pain due to osteoarthritis (OA). We aimed to characterize the role of the clock gene in OA-induced pain more systemically using both genetic and pharmacological approaches. Genetically modified mice, (bmal1f/fNav1.8CreERT mice), generated by deleting the critical clock gene, bmal1, from Nav1.8 sensory neurons, were resistant to the development of mechanical hyperalgesia associated with OA induced by partial medial meniscectomy (PMM) of the knee...
February 20, 2018: Gene
https://www.readbyqxmd.com/read/29401617/rev-erbs-agonism-suppresses-osteoclastogenesis-and-prevents-ovariectomy-induced-bone-loss-partially-via-fabp4-upregulation
#2
Chao Song, Peng Tan, Zheng Zhang, Wei Wu, Yonghui Dong, Liming Zhao, Huiyong Liu, Hanfeng Guan, Feng Li
REV-ERBs (REV-ERBα and REV-ERBβ) are transcription repressors and circadian regulators. Previous investigations have shown that REV-ERBs repress the expression of target genes, including MMP9 and CX3CR1, in macrophages. Because MMP9 and CX3CR1 reportedly participate in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, we inferred that REV-ERBs might play a role in osteoclastogenesis. In the present study, we found that the REV-ERBα level decreased significantly during RANKL-induced osteoclast differentiation from primary bone marrow-derived macrophages (BMMs)...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29365732/role-of-the-nuclear-receptor-rev-erb-alpha-in-the-development-of-vascular-calcification
#3
Mathilde Zecchin, Benoit Pourcet, Lise Ferri, Jonathan Vanhoutte, Stéphane Delhaye, Bart Staels, Hélène Duez
No abstract text is available yet for this article.
August 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29355503/rev-erb%C3%AE-is-required-to-maintain-normal-wakefulness-and-the-wake-inducing-effect-of-dual-rev-erb-agonist-sr9009
#4
Ariadna Amador, Theodore M Kamenecka, Laura A Solt, Thomas P Burris
Circadian signaling regulates and synchronizes physiological and behavioral processes, such as feeding, metabolism, and sleep cycles. The endogenous molecular machinery that regulates circadian activities is located in the suprachiasmatic nucleus of the hypothalamus. The REV-ERBs are transcription factors that play key roles in the regulation of the circadian clock and metabolism. Using pharmacological methods, we recently demonstrated the involvement of the REV-ERBs in sleep architecture. Another group reported a delayed response to sleep deprivation and altered sleep cycles in REV-ERBα null mice, indicating a role of REV-ERBα in sleep...
January 17, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29352049/rev-erb-agonists-block-autophagy-in-cancer-cells
#5
(no author information available yet)
Disruption of the circadian clock components reduces cancer cell viability in vitro and in vivo.
January 19, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29331507/adropin-an-endocrine-link-between-the-biological-clock-and-cholesterol-homeostasis
#6
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...
December 30, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#7
Gabriele Sulli, Amy Rommel, Xiaojie Wang, Matthew J Kolar, Francesca Puca, Alan Saghatelian, Maksim V Plikus, Inder M Verma, Satchidananda Panda
The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock...
January 18, 2018: Nature
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#8
Endin Nokik Stujanna, Nobuyuki Murakoshi, Kazuko Tajiri, DongZhu Xu, Taizo Kimura, Rujie Qin, Duo Feng, Saori Yonebayashi, Yukino Ogura, Fumi Yamagami, Akira Sato, Akihiko Nogami, Kazutaka Aonuma
Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered...
2017: PloS One
https://www.readbyqxmd.com/read/29215066/pharmacological-inhibition-of-rev-erb-stimulates-differentiation-inhibits-turnover-and-reduces-fibrosis-in-dystrophic-muscle
#9
Ryan D Welch, Cyrielle Billon, Aurore-Cecile Valfort, Thomas P Burris, Colin A Flaveny
Duchenne muscular dystrophy (DMD) is a debilitating X-linked disorder that is fatal. DMD patients lack the expression of the structural protein dystrophin caused by mutations within the DMD gene. The absence of functional dystrophin protein results in excessive damage from normal muscle use due to the compromised structural integrity of the dystrophin associated glycoprotein complex. As a result, DMD patients exhibit ongoing cycles of muscle destruction and regeneration that promote inflammation, fibrosis, mitochondrial dysfunction, satellite cell (SC) exhaustion and loss of skeletal and cardiac muscle function...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28990415/redox-regulation-of-heme-oxygenase-2-and-the-transcription-factor-rev-erb-through-heme-regulatory-motifs
#10
Angela S Fleischhacker, Eric L Carter, Stephen W Ragsdale
SIGNIFICANCE: Heme binds to and serves as a cofactor for a myriad of proteins that are involved in diverse biological processes. Hemoproteins also exhibit varying modes of heme binding, suggesting that the 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...
November 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28878135/rev-erb%C3%AE-ameliorates-heart-failure-through-transcription-repression
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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