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https://www.readbyqxmd.com/read/28599788/nr1d1-enhances-oxidative-dna-damage-by-inhibiting-parp1-activity
#1
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...
June 6, 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
#2
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
#3
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
#4
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...
May 13, 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
#5
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
#6
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
#7
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...
April 6, 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
#8
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
https://www.readbyqxmd.com/read/28262759/role-of-a-circadian-relevant-gene-nr1d1-in-brain-development-possible-involvement-in-the-pathophysiology-of-autism-spectrum-disorders
#9
Masahide Goto, Makoto Mizuno, Ayumi Matsumoto, Zhiliang Yang, Eriko F Jimbo, Hidenori Tabata, Takanori Yamagata, Koh-Ichi Nagata
In our previous study, we screened autism spectrum disorder (ASD) patients with and without sleep disorders for mutations in the coding regions of circadian-relevant genes, and detected mutations in several clock genes including NR1D1. Here, we further screened ASD patients for NR1D1 mutations and identified three novel mutations including a de novo heterozygous one c.1499 G > A (p.R500H). We then analyzed the role of Nr1d1 in the development of the cerebral cortex in mice. Acute knockdown of mouse Nr1d1 with in utero electroporation caused abnormal positioning of cortical neurons during corticogenesis...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28249904/nr1d1-recruitment-to-sites-of-dna-damage-inhibits-repair-and-is-associated-with-chemosensitivity-of-breast-cancer
#10
Na-Lee Ka, Tae-Young Na, Hyelin Na, Min-Ho Lee, Han-Su Park, Sewon Hwang, Il Yong Kim, Je Kyung Seong, Mi-Ock Lee
DNA repair capacity is critical for survival of cancer cells upon therapeutic DNA damage and thus is an important determinant of susceptibility to chemotherapy in cancer patients. In this study, we identified a novel function of nuclear receptor NR1D1 in DNA repair, which enhanced chemosensitivity in breast cancer cells. NR1D1 inhibited both nonhomologous end joining and homologous recombination double-strand breaks repair, and delayed the clearance of γH2AX DNA repair foci that formed after treatment of doxorubicin...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28095742/lithium-response-in-bipolar-disorders-and-core-clock-genes-expression
#11
Pierre A Geoffroy, Emmanuel Curis, Cindie Courtin, Jeverson Moreira, Thomas Morvillers, Bruno Etain, Jean-Louis Laplanche, Frank Bellivier, Cynthia Marie-Claire
OBJECTIVES: We examine if the lithium response is associated with changes in core clock genes expressions. METHODS: The effect of a therapeutic concentration of lithium (1mM) on the expression levels of 17 circadian genes, was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of BD patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) were conducted at 2, 4 and 8 days (d2, d4, d8) with and without lithium exposure...
January 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28045078/positive-association-between-physical-activity-and-per3-expression-in-older-adults
#12
Masaki Takahashi, Atsushi Haraguchi, Yu Tahara, Natsumi Aoki, Mayuko Fukazawa, Kumpei Tanisawa, Tomoko Ito, Takashi Nakaoka, Mitsuru Higuchi, Shigenobu Shibata
The circadian clock regulates many physiological functions including physical activity and feeding patterns. In addition, scheduled exercise and feeding themselves can affect the circadian clock. The purpose of the present study was to investigate the relationship between physical/feeding activity and expression of clock genes in hair follicle cells in older adults. Twenty adult men (age, 68 ± 7 years, mean ± SE) were examined in this cross-sectional study. Prior to hair follicle cell collection, the participants were asked to wear a uniaxial accelerometer for one week...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27997226/dysregulation-of-metallothionein-and-circadian-genes-in-human-hepatocellular-carcinoma
#13
Huan Li, Yuan-Fu Lu, Hong Chen, Jie Liu
Hepatocellular carcinoma (HCC) is the major threat to human health, and disruption of circadian clock genes is implicated in hepatocarcinogenesis. This study examined the dysregulation of metallothioneins and circadian genes in achieved human HCC (n = 24), peri-HCC tissues (n = 24) as compared with normal human livers (n = 36). Total RNA was extracted and reverse transcribed. Real-time RT-qPCR was performed to determine the expression of genes of interest. The results demonstrated the downregulation of metallothionein-1 (MT-1), MT-2, and metal transcription factor-1 (MFT-1) in human HCC as compared with Peri-HCC and normal tissues...
2017: Chronobiology International
https://www.readbyqxmd.com/read/27988807/effects-of-bright-light-exposure-during-daytime-on-peripheral-clock-gene-expression-in-humans
#14
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...
December 17, 2016: International Journal of Biometeorology
https://www.readbyqxmd.com/read/27931190/daily-rhythmicity-of-clock-gene-transcript-levels-in-fast-and-slow-muscle-fibers-from-chinese-perch-siniperca-chuatsi
#15
Ping Wu, Yu-Long Li, Jia Cheng, Lin Chen, Xin Zhu, Zhi-Guo Feng, Jian-She Zhang, Wu-Ying Chu
BACKGROUND: Clock genes are considered to be the molecular core of biological clock in vertebrates and they are directly involved in the regulation of daily rhythms in vertebrate tissues such as skeletal muscles. Fish myotomes are composed of anatomically segregated fast and slow muscle fibers that possess different metabolic and contractile properties. To date, there is no report on the characterization of the circadian clock system components of slow muscles in fish. RESULTS: In the present study, the molecular clock components (clock, arntl1/2, cry1/2/3, cry-dash, npas2, nr1d1/2, per1/2/3, rorα and tim genes) and their daily transcription levels were characterized in slow and fast muscles of Chinese perch (Siniperca chuatsi)...
December 8, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27884645/dysregulated-circadian-rhythm-pathway-in-human-osteoarthritis-nr1d1-and-bmal1-suppression-alters-tgf-%C3%AE-signaling-in-chondrocytes
#16
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...
June 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27720799/deletion-of-exons-3-and-4-in-the-mouse-nr1d1-gene-worsens-high-fat-diet-induced-hepatic-steatosis
#17
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...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27686098/rev-erb%C3%AE-influences-the-stability-and-nuclear-localization-of-the-glucocorticoid-receptor
#18
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
https://www.readbyqxmd.com/read/27661138/mechanisms-of-hormonal-regulation-of-the-peripheral-circadian-clock-in-the-colon
#19
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...
2017: Chronobiology International
https://www.readbyqxmd.com/read/27618422/corticosteroid-fludrocortisone-acetate-targets-multiple-end-points-in-zebrafish-danio-rerio-at-low-concentrations
#20
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
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