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https://www.readbyqxmd.com/read/29320480/pharmacological-activation-of-rev-erbs-is-lethal-in-cancer-and-oncogene-induced-senescence
#1
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
#2
B Pourcet, M Zecchin, L Ferri, J Beauchamp, S Sitaula, C Billon, S Delhaye, J Vanhoutte, A Mayeuf-Louchart, Q Thorel, J Haas, J Eeckhoute, D Dombrowicz, C Duhem, A Boulinguiez, S Lancel, Y Sebti, T Burris, B Staels, H 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...
December 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29232411/rev-erb-agonist-improves-adverse-cardiac-remodeling-and-survival-in-myocardial-infarction-through-an-anti-inflammatory-mechanism
#3
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/29190094/active-glucocorticoids-have-a-range-of-important-adverse-developmental-and-physiological-effects-on-developing-zebrafish-embryos
#4
Raffael Alois Willi, Susanne Faltermann, Timm Hettich, Karl Fent
Glucocorticoids in aquatic systems originating from natural excretion and medical use may pose a risk to fish. Here, we analyzed physiological and transcriptional effects of clobetasol propionate (CLO), cortisol and cortisone in zebrafish embryos as single compounds and binary mixtures. CLO and cortisol, but not cortisone showed a concentration-dependent decrease in muscle contraction, increase in heart rate, and accelerated hatching. CLO also induced immobilization and edema at high concentrations. Transcription analysis covering up to 26 genes showed that mostly genes related to glucose metabolism, immune system and development were differentially expressed at 91 ng/L and higher...
December 22, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29186286/obesity-induced-changes-in-hepatic-and-placental-clock-gene-networks-in-rat-pregnancy
#5
Rachael C Crew, Brendan J Waddell, Peter J Mark
Maternal obesity induces pregnancy complications and disturbs fetal development, but the specific mechanisms underlying these outcomes are unclear. Circadian rhythms are implicated in metabolic complications associated with obesity, and maternal metabolic adaptations to pregnancy. Accordingly, obesity-induced circadian dysfunction may drive adverse outcomes in obese pregnancy. This study investigated whether maternal obesity alters the rhythmic expression of clock genes and associated nuclear receptors across maternal, fetal and placental tissues...
November 25, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29150901/expression-of-the-clock-gene-rev-erb%C3%AE-in-the-brain-controls-the-circadian-organization-of-food-intake-and-locomotor-activity-but-not-daily-variations-of-energy-metabolism
#6
Satish Sen, Stéphanie Dumont, Dominique Sage-Ciocca, Sophie Reibel, Paul de Goede, Andries Kalsbeek, Etienne Challet
The nuclear receptor REV-ERBα is part of the molecular clock mechanism and thought 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 constant darkness, and 24-h variations of Respiratory quotient (RQ) and energy expenditure, as well as the temporal patterns of rest-activity and feeding behavior were recorded...
November 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29111822/repercussions-of-hypo-and-hyperthyroidism-on-the-heart-circadian-clock
#7
Rodrigo A Peliciari-Garcia, Paula Bargi-Souza, Martin E Young, Maria Tereza Nunes
Myocardial gene expression and metabolism fluctuate over the course of the day in association with changes in energy supply and demand. Time-of-day-dependent oscillations in myocardial processes have been linked to the intrinsic cardiomyocyte circadian clock. Triiodothyronine (T3) is an important modulator of heart metabolism and function. Recently, our group has reported time-of-day-dependent rhythms in cardiac T3 sensitivity, as well as, T3-mediated acute alterations on core clock components. Hypo and hyperthyroidism are the second most prevalent endocrine disease worldwide...
November 7, 2017: Chronobiology International
https://www.readbyqxmd.com/read/28992598/global-transcriptomic-analysis-of-zebrafish-in-response-to-embryonic-exposure-to-three-antidepressants-amitriptyline-fluoxetine-and-mianserin
#8
Minghong Wu, Shuai Liu, Lei Hu, Haidong Qu, Chenyuan Pan, Penghui Lei, Yingjia Shen, Ming Yang
Antidepressants are among the most commonly detected pharmaceuticals in aqueous systems, and, as emerging organic pollutants, may exert negative effects on non-target aquatic organisms. Previously, it has been revealed that antidepressant exposure significantly inhibits the growth and development of fish during their early developmental stages. Thus, in the present study, we aimed to identify and compare the underlying mechanisms of action of different antidepressants at the transcriptional level using zebrafish (Danio rerio) embryos...
September 28, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28951217/assessing-molecular-initiating-events-mies-key-events-kes-and-modulating-factors-mfs-for-styrene-responses-in-mouse-lungs-using-whole-genome-gene-expression-profiling-following-1-day-and-multi-week-exposures
#9
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Patrick D McMullen
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP2F2(-/-) transgenic containing human CYP2F1, 2A13 and 2B6). Exposures were for 1-day and 1, 4 and 26weeks. After 1-day exposures at 1, 5, 10, 20, 40 and 120ppm significant increases in differentially expressed genes (DEGs) occurred only in parental strain lungs where there was already an increase in DEGs at 5ppm and then many thousands of DEGs by 120ppm...
November 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28944015/signatures-of-selection-in-mammalian-clock-genes-with-coding-trinucleotide-repeats-implications-for-studying-the-genomics-of-high-pace-adaptation
#10
Melanie B Prentice, Jeff Bowman, Jillian L Lalor, Michelle M McKay, Lindsay A Thomson, Cristen M Watt, Andrew G McAdam, Dennis L Murray, Paul J Wilson
Climate change is predicted to affect the reproductive ecology of wildlife; however, we have yet to understand if and how species can adapt to the rapid pace of change. Clock genes are functional genes likely critical for adaptation to shifting seasonal conditions through shifts in timing cues. Many of these genes contain coding trinucleotide repeats, which offer the potential for higher rates of change than single nucleotide polymorphisms (SNPs) at coding sites, and, thus, may translate to faster rates of adaptation in changing environments...
September 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28797239/nutrient-supply-affects-the-mrna-expression-profile-of-the-porcine-skeletal-muscle
#11
Tainã Figueiredo Cardoso, Raquel Quintanilla, Joan Tibau, Marta Gil, Emilio Mármol-Sánchez, Olga González-Rodríguez, Rayner González-Prendes, Marcel Amills
BACKGROUND: The genetic basis of muscle fat deposition in pigs is not well known. So far, we have only identified a limited number of genes involved in the absorption, transport, storage and catabolism of lipids. Such information is crucial to interpret, from a biological perspective, the results of genome-wide association analyses for intramuscular fat content and composition traits. Herewith, we have investigated how the ingestion of food changes gene expression in the gluteus medius muscle of Duroc pigs...
August 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28765524/bmal1-regulates-inflammatory-responses-in-macrophages-by-modulating-enhancer-rna-transcription
#12
Yumiko Oishi, Shinichiro Hayashi, Takayuki Isagawa, Motohiko Oshima, Atsushi Iwama, Shigeki Shimba, Hitoshi Okamura, Ichiro Manabe
Bmal1 (encoded by Arntl gene) is a core circadian clock gene that regulates various genes involved in circadian rhythm. Although Bmal1 is expressed rhythmically in macrophages, the role of Bmal1 in the regulation of their cellular function remains insufficiently understood. Here, we report that Bmal1 regulates time-dependent inflammatory responses following Toll-like receptor 4 (TLR4) activation by modulating enhancer activity. Global transcriptome analysis indicated that deletion of Arntl perturbed the time-dependent inflammatory responses elicited by TLR4 activation by Kdo2-lipid A (KLA)...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599788/nr1d1-enhances-oxidative-dna-damage-by-inhibiting-parp1-activity
#13
Na-Lee Ka, Tae-Young Na, Mi-Ock Lee
Cancer cells exhibit an elevated intracellular level of reactive oxygen species (ROS) because of their accelerated metabolism, mitochondrial dysfunction, and antioxidant deficit. The oxidative stress in cancer cells may provide clinical benefits, which can be associated with a better response to anticancer therapies. Therefore, identifying the regulatory pathway of oxidative stress in cancer cells is important in the development of therapeutic targets that enhance sensitivity to ROS-generating anticancer therapies...
October 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#14
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28513593/jak3-deficiency-blocks-innate-lymphoid-cell-development
#15
M L Robinette, M Cella, J B Telliez, T K Ulland, A D Barrow, K Capuder, S Gilfillan, L-L Lin, L D Notarangelo, M Colonna
Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1(tm1Ven)/LazJ mouse line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3, generating a SCID phenotype and an inability to generate antigen-independent professional cytokine-producing innate lymphoid cells (ILCs)...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28511934/repeated-manganese-administration-produced-abnormal-expression-of-circadian-clock-genes-in-the-hypothalamus-and-liver-of-rats
#16
Huan Li, Ximin Fan, Ying Luo, Sheng Song, Jie Liu, Qiyuan Fan
Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment like Parkinson's disease (PD), and is called as Manganism. Circadian disruption is a non-motor symptom found in PD and Manganism. Clock genes are essential to drive and maintain circadian rhythm, but little is known about Mn exposure on circadian clock genes expression. Both the brain and liver are targets of Mn, we hypothesize that repeated Mn administration could affect clock gene expression in the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally injected Mn(2+) 1mg and 5mg/kg as MnCl2·4H2O, every other day for 30 days...
September 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28419375/transcriptional-profiling-of-cholinergic-neurons-from-basal-forebrain-identifies-changes-in-expression-of-genes-between-sleep-and-wake
#17
Elena V Nikonova, Jason DA Gilliland, Keith Q Tanis, Alexei A Podtelezhnikov, Alison M Rigby, Raymond J Galante, Eva M Finney, David J Stone, John J Renger, Allan I Pack, Christopher J Winrow
Study objective: To assess differences in gene expression in cholinergic basal forebrain cells between sleeping and sleep-deprived mice sacrificed at the same time of day. Methods: Tg(ChAT-eGFP)86Gsat mice expressing enhanced green fluorescent protein (eGFP) under control of the choline acetyltransferase (Chat) promoter were utilized to guide laser capture of cholinergic cells in basal forebrain. Messenger RNA expression levels in these cells were profiled using microarrays...
June 1, 2017: Sleep
https://www.readbyqxmd.com/read/28412351/effect-of-apoa4-on-serpina3-mediated-by-nuclear-receptors-nr4a1-and-nr1d1-in-hepatocytes
#18
Yupeng Zhang, Jing He, Jing Zhao, Min Xu, Danwen Lou, Patrick Tso, Zongfang Li, Xiaoming Li
ApoA4 exerts anti-inflammatory effects, but the mechanism remains unclear. SERPINA3 is a member of the serine proteinase inhibitor gene family, and has been shown to be involved in anti-inflammation and associated with a number of human diseases. In this study, we revealed that ApoA4 stimulates the gene expression of SERPINA3 in mouse hepatocytes both in vivo and in vitro, in a dose- and time-dependent manner. The transcriptional response of SERPINA3 to ApoA4 is regulated through the binding of ApoA4 with nuclear receptors NR4A1 and NR1D1 on the SERPINA3 promoter, which was verified with ChIP, Luciferase activity assay and RNA interference-mediated NR4A1 or NR1D1 gene knockdown...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28392392/combining-transcriptomics-and-pbpk-modeling-indicates-a-primary-role-of-hypoxia-and-altered-circadian-signaling-in-dichloromethane-carcinogenicity-in-mouse-lung-and-liver
#19
Melvin E Andersen, Michael B Black, Jerry L Campbell, Salil N Pendse, Harvey J Clewell Iii, Lynn H Pottenger, James S Bus, Darol E Dodd, Daniel C Kemp, Patrick D McMullen
Dichloromethane (DCM) is a lung and liver carcinogen in mice at inhalation exposures≥2000ppm. The modes of action (MOA) of these responses have been attributed to formation of genotoxic, reactive metabolite(s). Here, we examined gene expression in lung and liver from female B6C3F1 mice exposed to 0, 100, 500, 2000, 3000 and 4000ppm DCM for 90days. We also simulated dose measures - rates of DCM oxidation to carbon monoxide (CO) in lung and liver and expected blood carboxyhemoglobin (HbCO) time courses with a PBPK model inclusive of both conjugation and oxidation pathways...
October 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28296937/effects-of-circadian-clock-genes-and-health-related-behavior-on-metabolic-syndrome-in-a-taiwanese-population-evidence-from-association-and-interaction-analysis
#20
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Shih-Jen Tsai
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population...
2017: PloS One
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