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R Akagi, Y Akatsu, K M Fisch, O Alvarez-Garcia, T Teramura, Y Muramatsu, M Saito, T Sasho, A I Su, M K Lotz
OBJECTIVES: Circadian rhythm (CR) was identified by RNA sequencing as the most dysregulated pathway in human osteoarthritis (OA) in articular cartilage. This study examined circadian rhythmicity in cultured chondrocytes and the role of the CR genes NR1D1 and BMAL1 in regulating chondrocyte functions. METHODS: RNA was extracted from normal and OA-affected human knee cartilage (n = 14 each). Expression levels of NR1D1 and BMAL1 mRNA and protein were assessed by quantitative PCR and immunohistochemistry...
November 22, 2016: Osteoarthritis and Cartilage
Hyelin Na, Ho Lee, Min-Ho Lee, Han Jeong Lim, Hyeon-Ji Kim, Yoon Jeon, Hae-Lim Kang, Mi-Ock Lee
AIMS: To elucidate the role of nuclear receptor subfamily 1, group D, member 1 (Nr1d1) in hepatic lipid metabolism and pathogenesis of nonalcoholic fatty liver diseases, Nr1d1 gene mutant mice, in which the DNA-binding domain (exons 3 and 4) was deleted (Nr1d1 Δex3/4), were challenged with a high-fat diet (HFD), and the gene expression patterns that responded to this alteration were profiled. MAIN METHODS: The Nr1d1 Δex3/4 mice were fed an HFD for 12weeks. Liver tissues were examined by histology, and lipid droplets were detected by Oil-Red O staining...
October 5, 2016: Life Sciences
Takashi Okabe, Rohit Chavan, Sara S Fonseca Costa, Andrea Brenna, Jürgen A Ripperger, Urs Albrecht
REV-ERBα (encoded by Nr1d1) is a nuclear receptor that is part of the circadian clock mechanism and regulates metabolism and inflammatory processes. The glucocorticoid receptor (GR, encoded by Nr3c1) influences similar processes, but is not part of the circadian clock, although glucocorticoid signaling affects resetting of the circadian clock in peripheral tissues. Because of their similar impact on physiological processes, we studied the interplay between these two nuclear receptors. We found that REV-ERBα binds to the C-terminal portion and GR to the N-terminal portion of HSP90α and HSP90β, a chaperone responsible for the activation of proteins to ensure survival of a cell...
November 1, 2016: Journal of Cell Science
Lenka Polidarová, Pavel Houdek, Martin Sládek, Zuzana Novosadová, Jiří Pácha, Alena Sumová
Colonic function is controlled by an endogenous clock that allows the colon to optimize its function on the daytime basis. For the first time, this study provided evidence that the clock is synchronized by rhythmic hormonal signals. In rat colon, adrenalectomy decreased and repeated applications of dexamethasone selectively rescued circadian rhythm in the expression of the clock gene Per1. Dexamethasone entrained the colonic clock in explants from mPer2(Luc) mice in vitro. In contrast, pinealectomy had no effect on the rat colonic clock, and repeated melatonin injections were not able to rescue the clock in animals maintained in constant light...
September 23, 2016: Chronobiology International
Yanbin Zhao, Kun Zhang, Karl Fent
Synthetic corticosteroids may pose an environmental risk to fish. Here, we describe multiend point responses of adult zebrafish (8 months old) upon 21-day exposure to a commonly prescribed corticosteroid, fludrocortisone acetate (FLU), at concentrations between 0.006 and 42 μg/L. No remarkable reproductive impacts were observed, while physiological effects, including plasma glucose level and blood leukocyte numbers were significant altered even at 42 ng/L. Ovary parameters and transcriptional analysis of hypothalamic-pituitary-gonadal-liver axis revealed negligible effects...
September 20, 2016: Environmental Science & Technology
Ouafa Ait-Hmyed Hakkari, Niyazi Acar, Elise Savier, Perrine Spinnhirny, Mohammed Bennis, Marie-Paule Felder-Schmittbuhl, Jorge Mendoza, David Hicks
The circadian clock is thought to adjust retinal sensitivity to ambient light levels, yet the involvement of specific clock genes is poorly understood. We explored the potential role of the nuclear receptor subfamily 1, group D, member 1 (REV-ERBα; or NR1D1) in this respect. In light-evoked behavioral tests, compared with wild-type littermates, Rev-Erbα(-/-) mice showed enhanced negative masking at low light levels (0.1 lux). Rev-Erbα(-/-) mouse retinas displayed significantly higher numbers of intrinsically photosensitive retinal ganglion cells (ipRGCs; 62% more compared with wild-type) and more intense melanopsin immunostaining of individual ipRGC cells...
July 20, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Guodong Huang, Fanmiao Zhang, Qiang Ye, Han Wang
Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. The mechanisms underlying circadian regulation of autophagy, however, are still unclear. Here, we observed that numbers of autophagosomes and autolysosomes exhibit daily rhythms in the zebrafish liver, and cebpb/(c/ebpβ) and various autophagy genes are rhythmically expressed in zebrafish larvae but significantly upregulated in per1b and TALEN-generated nr1d1/rev-erbα mutant fish, indicating that both Per1b and Nr1d1 play critical roles in autophagy rhythms...
August 2, 2016: Autophagy
Yichi Xu, Weimin Guo, Ping Li, Yan Zhang, Meng Zhao, Zenghua Fan, Zhihu Zhao, Jun Yan
Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver...
May 2016: PLoS Genetics
Hiroshi D Akashi, Antonio Cádiz Díaz, Shuji Shigenobu, Takashi Makino, Masakado Kawata
How animals achieve evolutionary adaptation to different thermal environments is an important issue for evolutionary biology as well as for biodiversity conservation in the context of recent global warming. In Cuba, three sympatric species of Anolis lizards (Anolis allogus, A. homolechis and A. sagrei) inhabit different thermal microhabitats, thereby providing an excellent opportunity to examine how they have adapted to different environmental temperatures. Here, we performed RNA-seq on the brain, liver and skin tissues from these three species to analyse their transcriptional responses at two different temperatures...
May 2016: Molecular Ecology
Ursula Loizides-Mangold, Marie Koren-Gluzer, Svetlana Skarupelova, Anne-Marie Makhlouf, Tony Hayek, Michael Aviram, Charna Dibner
The circadian timing system regulates key aspects of mammalian physiology. Here, we analyzed the effect of the endogenous antioxidant paraoxonase 1 (PON1), a high-density lipoprotein-associated lipolactonase that hydrolyses lipid peroxides and attenuates atherogenesis, on circadian gene expression in C57BL/6J and PON1KO mice fed a normal chow diet or a high-fat diet (HFD). Expression levels of core-clock transcripts Nr1d1, Per2, Cry2 and Bmal1 were altered in skeletal muscle in PON1-deficient mice in response to HFD...
2016: Chronobiology International
Jeverson Moreira, Pierre Alexis Geoffroy
Bipolar disorder (BD) is a severe and common psychiatric disorder. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. Lithium (Li) is the first-line treatment in BD, and its therapeutic action has been related to its ability to alter circadian rhythms. We systematically searched the PubMed database until January 2016, aiming to critically examine published studies investigating direct and indirect effects of Li on circadian rhythms. The results, from the 95 retained studies, indicated that Li: acts directly on the molecular clocks; delays the phase of sleep-wakefulness rhythms and the peak elevation of diurnal cycle body temperature; reduces the amplitude and shortens the duration of activity rhythms and lengthens free-running rhythms...
2016: Chronobiology International
Gianluigi Mazzoccoli, Rosa Rubino, Cristiana Tiberio, Francesco Giuliani, Manlio Vinciguerra, Jude Oben, Angelo De Cata, Roberto Tarquini, Salvatore De Cosmo, Shu Liu, Yanning Cai
The biological hard-wiring of 24-hour rhythmicity relies on the circadian clock circuitry, made of peripheral oscillators operated by molecular clockworks and synchronized through humoral and neural outputs by central oscillators located in the hypothalamic suprachiasmatic nuclei. Metabolically active tissues, such as the liver, are entrained also by local cues represented by metabolic flux related to feeding. The mechanics of the molecular clockwork have been explored by studies using cell lines and wild type or genetically engineered mouse models...
2016: Chronobiology International
O Pivovarova, Ö Gögebakan, S Sucher, J Groth, V Murahovschi, K Kessler, M Osterhoff, N Rudovich, A Kramer, A F H Pfeiffer
BACKGROUND: The circadian clock coordinates numerous metabolic processes to adapt physiological responses to light-dark and feeding regimens and is itself regulated by metabolic cues. The implication of the circadian clock in the regulation of energy balance and body weight is widely studied in rodents but not in humans. Here we investigated (1) whether the expression of clock genes in human adipose tissue is changed by weight loss and (2) whether these alterations are associated with metabolic parameters...
June 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Enrico Garattini, Marco Bolis, Maurizio Gianni', Gabriela Paroni, Maddalena Fratelli, Mineko Terao
Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer...
July 5, 2016: Oncotarget
Mirian Samblas, Fermin I Milagro, Purificación Gómez-Abellán, J Alfredo Martínez, Marta Garaulet
The circadian clock system has been linked to the onset and development of obesity and some accompanying comorbidities. Epigenetic mechanisms, such as DNA methylation, are putatively involved in the regulation of the circadian clock system. The aim of this study was to investigate the influence of a weight loss intervention based on an energy-controlled Mediterranean dietary pattern in the methylation levels of 3 clock genes, BMAL1, CLOCK, and NR1D1, and the association between the methylation levels and changes induced in the serum lipid profile with the weight loss treatment...
June 2016: Journal of Biological Rhythms
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
Shaon Sengupta, Guang Yang, John C O'Donnell, Maurice D Hinson, Shana E McCormack, Marni J Falk, Ping La, Michael B Robinson, Monica L Williams, Mekdes T Yohannes, Erzsebet Polyak, Eiko Nakamaru-Ogiso, Phyllis A Dennery
Diurnal oscillations in the expression of antioxidant genes imply that protection against oxidative stress is circadian-gated. We hypothesized that stabilization of the core circadian gene Rev-erbα (Nr1d1) improves cellular bioenergetics and protects against nutrient deprivation and oxidative stress. Compared to WT, mouse lung fibroblasts (MLG) stably transfected with a degradation resistant Rev-erbα (Ser(55/59) to Asp; hence referred to as SD) had 40% higher protein content, 1.5-fold higher mitochondrial area (confocal microscopy), doubled oxidative phosphorylation by high-resolution respirometry (Oroboros) and were resistant to glucose deprivation for 24h...
April 2016: Free Radical Biology & Medicine
Ali Khammanivong, Arunkumar Anandharaj, Xuemin Qian, Jung Min Song, Pramod Upadhyaya, Silvia Balbo, Dipankar Bandyopadhyay, Erin B Dickerson, Stephen S Hecht, Fekadu Kassie
Recently, we have shown that (S)-N'-Nitrosonornicotine [(S)-NNN], the major form of NNN in tobacco products, is a potent oral cavity and esophageal carcinogen in rats. To determine the early molecular alterations induced by (S)-NNN in the oral and esophageal mucosa, we administered the carcinogen to rats in the drinking water for 10 wk and global gene expression alterations were analyzed by RNA sequencing. At a false discovery rate P-value < 0.05 and fold-change ≥2, we found alterations in the level of 39 genes in the oral cavity and 69 genes in the esophagus...
December 2016: Molecular Carcinogenesis
S Yeim, C Boudebesse, B Etain, F Belliviera
INTRODUCTION: Bipolar disorder is a severe and complex multifactorial disease, characterized by alternance of acute episodes of depression and mania/hypomania, interspaced by euthymic periods. The etiological determinants of bipolar disorder yet, are still poorly understood. For the last 30 years, chronobiology is an important field of investigation to better understand the pathophysiology of bipolar disorder. METHODS: We conducted a review using Medline, ISI Database, EMBase, PsyInfo up to January 2015, using the following keywords combinations: "mood disorder", "bipolar disorder", "depression", "unipolar disorder", "major depressive disorder", "affective disorder", for psychiatric conditions; and "circadian rhythms", "circadian markers", "circadian gene", "clock gene", "melatonin" for circadian rhythms...
September 2015: L'Encéphale
Andrea de Faria F Belone, Patrícia S Rosa, Ana P F Trombone, Luciana R V Fachin, Cássio C Guidella, Somei Ura, Jaison A Barreto, Mabel G Pinilla, Alex F de Carvalho, Dirce M Carraro, Fernando A Soares, Cleverson T Soares
Leprosy, an infectious disease caused by Mycobacterium leprae, affects millions of people worldwide. However, little is known regarding its molecular pathophysiological mechanisms. In this study, a comprehensive assessment of human mRNA was performed on leprosy skin lesions by using DNA chip microarrays, which included the entire spectrum of the disease along with its reactional states. Sixty-six samples from leprotic lesions (10TT, 10BT, 10BB, 10BL, 4LL, 14R1, and 10R2) and nine skin biopsies from healthy individuals were used as controls (CC) (ages ranged from 06 to 83 years, 48 were male and 29 female)...
2015: Frontiers in Genetics
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