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https://www.readbyqxmd.com/read/29892224/melatonin-attenuates-dysregulation-of-the-circadian-clock-pathway-in-mice-with-ccl-4-induced-fibrosis-and-human-hepatic-stellate-cells
#1
Bárbara González-Fernández, Diana I Sánchez, Irene Crespo, Beatriz San-Miguel, Juan Ortiz de Urbina, Javier González-Gallego, María J Tuñón
Dysregulation of the circadian clock machinery is a critical mechanism in the pathogenesis of fibrosis. This study aimed to investigate whether the antifibrotic effect of melatonin is associated with attenuation of circadian clock pathway disturbances in mice treated with carbon tetrachloride (CCl4 ) and in human hepatic stellate cells line LX2. Mice received CCl4 5 μL/g body weight i.p. twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg/kg/day i.p., beginning 2 weeks after the start of CCl4 administration...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#2
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29590657/angiotensin-ii-suppresses-rev-erb%C3%AE-expression-in-thp-1-macrophages-via-the-ang-ii-type-1-receptor-liver-x-receptor-%C3%AE-pathway
#3
Shipeng Wang, Xia Gu, Qi Zhang, Xiling Zhang, Yilan Li, Yuan Yao, Bo Yu, Yao Zhang
BACKGROUND/AIMS: Angiotensin II (Ang II) regulates the expression of some core clock genes; excess Ang II leads to atherosclerosis advancement. Macrophage Rev-erbα mediates clockwork and inflammation, and plays a role in atherosclerotic lesion progression. However, the role of Ang II in regulating Rev-erbα expression in macrophages remains unclarified. METHODS: We induced THP-1 macrophages by phorbol 12-myristate 13-acetate and investigated the effect of Ang II on Rev-erbα expression via real-time polymerase chain reaction, western blotting and small interfering RNA (siRNA) techniques...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29474860/pharmacological-targeting-of-the-mammalian-clock-reveals-a-novel-analgesic-for-osteoarthritis-induced-pain
#4
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...
May 20, 2018: Gene
https://www.readbyqxmd.com/read/29401617/rev-erbs-agonism-suppresses-osteoclastogenesis-and-prevents-ovariectomy-induced-bone-loss-partially-via-fabp4-upregulation
#5
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/29355503/rev-erb%C3%AE-is-required-to-maintain-normal-wakefulness-and-the-wake-inducing-effect-of-dual-rev-erb-agonist-sr9009
#6
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...
April 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29331507/adropin-an-endocrine-link-between-the-biological-clock-and-cholesterol-homeostasis
#7
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
https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#8
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/29277561/nuclear-receptor-subfamily-1-group-d-member-1-regulates-circadian-activity-of-nlrp3-inflammasome-to-reduce-the-severity-of-fulminant-hepatitis-in-mice
#9
Benoit Pourcet, Mathilde Zecchin, Lise Ferri, Justine Beauchamp, Sadicha Sitaula, Cyrielle Billon, Stéphane Delhaye, Jonathan Vanhoutte, Alicia Mayeuf-Louchart, Quentin Thorel, Joel T Haas, Jérome Eeckhoute, David Dombrowicz, Christian Duhem, Alexis Boulinguiez, Steve Lancel, Yasmine Sebti, Thomas P Burris, Bart Staels, Hélène M Duez
BACKGROUND & AIMS: The innate immune system responds not only to bacterial signals, but also to non-infectious danger-associated molecular patterns that activate the NLRP3 inflammasome complex after tissue injury. Immune functions vary over the course of the day, but it is not clear whether these changes affect the activity of the NLRP3 inflammasome. We investigated whether the core clock component nuclear receptor subfamily 1 group D member 1 (NR1D1, also called Rev-erbα) regulates expression, activity of the NLRP3 inflammasome, and its signaling pathway...
April 2018: Gastroenterology
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#10
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/29183075/chemical-composition-and-labeling-of-substances-marketed-as-selective-androgen-receptor-modulators-and-sold-via-the-internet
#11
Ryan M Van Wagoner, Amy Eichner, Shalender Bhasin, Patricia A Deuster, Daniel Eichner
Importance: Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective: To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels...
November 28, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28223222/disrupting-the-key-circadian-regulator-clock-leads-to-age-dependent-cardiovascular-disease
#12
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
#13
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/27706103/in-vitro-metabolic-studies-of-rev-erb-agonists-sr9009-and-sr9011
#14
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
#15
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
https://www.readbyqxmd.com/read/26963516/pharmacological-and-genetic-modulation-of-rev-erb-activity-and-expression-affects-orexigenic-gene-expression
#16
Ariadna Amador, Yongjun Wang, Subhashis Banerjee, Theodore M Kameneka, Laura A Solt, Thomas P Burris
The nuclear receptors REV-ERBα and REV-ERBβ are transcription factors that play pivotal roles in the regulation of the circadian rhythm and various metabolic processes. The circadian rhythm is an endogenous mechanism, which generates entrainable biological changes that follow a 24-hour period. It regulates a number of physiological processes, including sleep/wakeful cycles and feeding behaviors. We recently demonstrated that REV-ERB-specific small molecules affect sleep and anxiety. The orexinergic system also plays a significant role in mammalian physiology and behavior, including the regulation of sleep and food intake...
2016: PloS One
https://www.readbyqxmd.com/read/26842585/emerging-drugs-affecting-skeletal-muscle-function-and-mitochondrial-biogenesis-potential-implications-for-sports-drug-testing-programs
#17
Mario Thevis, Wilhelm Schänzer
RATIONALE: A plethora of compounds potentially leading to drug candidates that affect skeletal muscle function and, more specifically, mitochondrial biogenesis, has been under (pre)clinical investigation for rare as well as more common diseases. Some of these compounds could be the object of misuse by athletes aiming at artificial and/or illicit and drug-facilitated performance enhancement, necessitating preventive and proactive anti-doping measures. METHODS: Early warnings and the continuous retrieval and dissemination of information are crucial for sports drug testing laboratories as well as anti-doping authorities, as they assist in preparation of efficient doping control analytical strategies for potential future threats arising from new therapeutic developments...
March 15, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/26616049/stimulation-of-nuclear-receptor-rev-erbs-regulates-tumor-necrosis-factor-induced-expression-of-proinflammatory-molecules-in-c6-astroglial-cells
#18
Norimitsu Morioka, Mizuki Tomori, Fang Fang Zhang, Munenori Saeki, Kazue Hisaoka-Nakashima, Yoshihiro Nakata
Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF)...
January 8, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25800870/suppression-of-atherosclerosis-by-synthetic-rev-erb-agonist
#19
Sadichha Sitaula, Cyrielle Billon, Theodore M Kamenecka, Laura A Solt, Thomas P Burris
The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice...
May 8, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/24355794/a-study-on-circadian-rhythm-disorder-of-rat-lung-tissue-caused-by-mechanical-ventilation-induced-lung-injury
#20
Huan Li, Chunxiao Wang, Jiaqi Hu, Junyuan Tan
Ventilator-induced lung injury (VILI), the most serious complication of mechanical ventilation therapy, is an excessive inflammatory response in lung tissue characterized by infiltration of inflammatory cells and overproduction of inflammatory mediators. The pathogenesis of VILI is very complex. It is becoming increasingly evident that disruption of circadian rhythm affects the immune response. Whether the pathogenesis of VILI is associated with circadian rhythm disruption has not been reported. In this study, we establish VILI model in SD rat by performing an endotracheal intubation and placing the rat on a mechanical ventilator (tidal volume of 40 ml/kg or 10 ml/kg without positive end-expiratory pressure)...
February 2014: International Immunopharmacology
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