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Song Wu, Andrew Fesler, Jingfang Ju
AIM: To establish a connection between microRNA (miRNAs), circadian rhythm, and colorectal cancer patient survival. METHODS: Genomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) colorectal cancer database, and the expression levels of candidate miRNAs and a set of circadian rhythm-related genes (Per1, Per2, Per3, Bmal1), and genes associated with chemosensitivity (thymidylate synthase, dihydrofolate reductase) were assessed for any correlations among their expression...
January 2016: Cancer Transl Med
Łukasz Mokros, Michał Seweryn Karbownik, Katarzyna Nowakowska-Domagała, Janusz Szemraj, Łukasz Wieteska, Karol Woźniak, Andrzej Witusik, Adam Antczak, Tadeusz Pietras
Background: There is barely any evidence of antipsychotic drugs affecting the molecular clockwork in human, yet it is suggested that clock genes are associated with dopaminergic transmission, i.e. the main target of this therapeutics. We decided to verify if haloperidol and olanzapine affect expression of CLOCK, BMAL1, PER1 and CRY1 in a human central nervous system cell line model. Methods: U-87MG human glioblastoma cell line was used as an experimental model. The cells were incubated with or without haloperidol and olanzapine in the concentration of 5 and 20 μM for 24 h...
November 1, 2016: Biological Rhythm Research
Malini Riddle, Erica Mezias, Duncan Foley, Joseph LeSauter, Rae Silver
The hypothalamic suprachiasmatic nucleus (SCN), locus of the master circadian clock, bears many neuronal types. At the cellular-molecular level, the clock is comprised of feedback loops involving "clock" genes including Period1 and Period2, and their protein products, PERIOD1 and PERIOD2 (PER1/2). In the canonical model of circadian oscillation, the PER1/2 proteins oscillate together. While their rhythmic expression in the SCN as a whole has been described, the possibility of regional differences is unknown...
October 14, 2016: European Journal of Neuroscience
Ryota Nakazato, Shogo Hotta, Daisuke Yamada, Miki Kou, Saki Nakamura, Yoshifumi Takahata, Hajime Tei, Rika Numano, Akiko Hida, Shigeki Shimba, Michihiro Mieda, Eiichi Hinoi, Yukio Yoneda, Takeshi Takarada
Similar to neurons, microglia have an intrinsic molecular clock. The master clock oscillator Bmal1 modulates interleukin-6 upregulation in microglial cells exposed to lipopolysaccharide. Bmal1 can play a role in microglial inflammatory responses. We previously demonstrated that gliotransmitter ATP induces transient expression of the clock gene Period1 via P2X7 purinergic receptors in cultured microglia. In this study, we further investigated mechanisms underlying the regulation of pro-inflammatory cytokine production by clock molecules in microglial cells...
October 11, 2016: Glia
Zsolt Nagy, Alexa Marta, Henriett Butz, Istvan Liko, Karoly Racz, Attila Patocs
Peripheral clocks are set by different nervous, hormonal and metabolic stimuli, and regulate the circadian expression of several genes. We investigated whether a peripheral clock could be induced in the human adrenocortical cell line H295R and whether glucocorticoid receptor isoforms (GRα and GRß) are involved in this clock system. After synchronization of cells with serum shock, the rhythmic oscillation of clock genes PER1, PER2, REV-ERBα, and ARNTL was confirmed. In addition, H295R cells even without serum shock showed rhythmic expression of PER1, PER2, CRY1 and ARNTL...
October 7, 2016: Steroids
Takafumi Katsumura, Yukiko Fukuyo, Shoji Kawamura, Hiroki Oota
BACKGROUND: The circadian clock is set up around a 24-h period in humans who are awake in the daytime and sleep in the nighttime, accompanied with physiological and metabolic rhythms. Most haplorhine primates, including humans, are diurnal, while most "primitive" strepsirrhine primates are nocturnal, suggesting primates have evolved from nocturnal to diurnal habits. The mechanisms of physiological changes causing the habits and of genetic changes causing the physiological changes are, however, unknown...
September 28, 2016: Journal of Physiological Anthropology
Satish Sen, Hélène Raingard, Stéphanie Dumont, Andries Kalsbeek, Patrick Vuillez, Etienne Challet
Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock (PER1) and clock-controlled (vasopressin) proteins. To determine if these SCN changes are due to the metabolic or timing cues of the restricted feeding, mice were challenged with an ultradian 6-meals schedule (1 food access every 4 h) to abolish the daily periodicity of feeding...
September 26, 2016: Chronobiology International
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
Zsofia Kiss, Paramita M Ghosh
The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison to those working regular hours. The common finding in these 'high-risk' groups was that they all experienced a deregulation of the body's internal circadian rhythm. Here we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression...
September 22, 2016: Endocrine-related Cancer
K Solocinski, M Holzworth, X Wen, K-Y Cheng, I J Lynch, B D Cain, C S Wingo, M L Gumz
AIM: Increasing evidence demonstrates that circadian clock proteins are important regulators of physiological functions including blood pressure. An established risk factor for developing cardiovascular disease is the absence of a blood pressure dip during the inactive period. The goal of the present study was to determine the effects of a high salt diet plus mineralocorticoid on PER1-mediated blood pressure regulation in a salt-resistant, normotensive mouse model, C57BL/6J. METHODS: Blood pressure was measured using radiotelemetry...
September 16, 2016: Acta Physiologica
Li Chang, Lan Li, Wenhui Li, Meiping Jiang, Yunhe Jv, Li Wang, Yu Hou, Qing Long, Shuhui Yu
PURPOSE: To investigate the radiation effects and acute damage in inoperable cervical cancer patients irradiated at different times as well as the underlying mechanisms. METHODS: 67 patients were randomized to a morning group (MG, 9:00 - 11:00 AM) and an evening group (EG, 9:00 - 11:00 PM) and both received external beam radiotherapy (RT) (50 Gy in 25 fractions) at different times. Brachytherapy (36 - 42 Gy in 6 - 7 fractions) was also performed to enhance the radiation response twice every week in all patients at the same time...
September 12, 2016: International Journal of Clinical Pharmacology and Therapeutics
Hiroyuki Tamiya, Sumito Ogawa, Yasuyoshi Ouchi, Masahiro Akishita
Period circadian clock (Per) genes Per1 and Per2 have essential roles in circadian oscillation. In this study, we identified a new role of Per1-Per2 cooperation, and its mechanism, using our new experimental methods. Under constant light conditions, the period length of Per1 and Per2 knockout mice depended on the copy number ratio of Per1:Per2. We then established a light-emitting diode-based lighting system that can generate any pattern of light intensity. Under gradually changing light in the absence of phase shift with different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a broader range of period length than wild-type mice...
2016: Scientific Reports
Qin Zhao, Gang Zheng, Kai Yang, Yi-Ran Ao, Xiao-Li Su, Yu Li, Xiao-Qiang Lv
The various clock genes in normal cells, through their interaction, establish a number of positive and negative feedback loops that compose a network structure. These genes play an important role in regulating normal physiological activities. The expression of clock gene PER1 is decreased in many types of cancer. PER1 is highly correlated with the initiation and progression of cancer by regulating numerous downstream genes. However, it is still unclear whether the lower expression of PER1 in cancer can influence the expression of other clock genes in the clock gene network...
September 2, 2016: Oncotarget
Jeff R Jones, Douglas G McMahon
The brain's biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAA receptor-mediated synaptic activity...
2016: PeerJ
Minkyung Kim, Hoyeon Lee, Jin-Hoe Hur, Joonho Choe, Chunghun Lim
Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophila CRTC in sustaining circadian behaviors. Genomic deletion of the crtc locus causes long but poor locomotor rhythms in constant darkness. Overexpression or RNA interference-mediated depletion of CRTC in circadian pacemaker neurons similarly impairs the free-running behavioral rhythms, implying that Drosophila clocks are sensitive to the dosage of CRTC...
2016: Scientific Reports
Laura K Fonken, Meagan M Kitt, Andrew D Gaudet, Ruth M Barrientos, Linda R Watkins, Steven F Maier
Aged animals exhibit diminished circadian rhythms, and both aging and circadian disruption sensitize neuroinflammatory responses. Microglia-the innate immune cell of the central nervous system-possess endogenous timekeeping mechanisms that regulate immune responses. Here, we explored whether aging is associated with disrupted diurnal rhythms in microglia and neuroinflammatory processes. First, hippocampal microglia isolated from young rats (4 months F344XBN) rhythmically expressed circadian clock genes, whereas microglia isolated from the hippocampus of aged rats (25 months) had aberrant Per1 and Per2 rhythms...
August 1, 2016: Neurobiology of Aging
Hasna Lahouaoui, Christine Coutanson, Howard M Cooper, Mohamed Bennis, Ouria Dkhissi-Benyahya
PURPOSE: Diabetic retinopathy is one of the most common consequences of diabetes that affects millions of working-age adults worldwide and leads to progressive degeneration of the retina, visual loss, and blindness. Diabetes is associated with circadian disruption of the central and peripheral circadian clocks, but the mechanisms responsible for such alterations are unknown. Using a streptozotocin (STZ)-induced model of diabetes, we investigated whether diabetes alters 1) the circadian regulation of clock genes in the retina and in the central clocks, 2) the light response of clock genes in the retina, and/or 3) light-driven retinal dopamine (DA), a major output marker of the retinal clock...
2016: Molecular Vision
Seung-Hee Yoo, Kristin Eckel-Mahan
Studies have demonstrated a pronounced dependence of memory formation on circadian time; however, the numerous mechanisms underlying this reliance are only beginning to be understood. While the 24-h cellular clock controls various aspects of hippocampal memory formation, its consolidation in particular (i.e., its conversion from short-term to long-term memory), appears to be heavily dependent on circadian activity in hippocampal neurons. Hippocampal memory consolidation requires phosphorylation of the cAMP Response Element-Binding protein, CREB, which upon phosphorylation promotes the transcription of genes necessary for long-term memory formation...
September 2016: Journal of Neurochemistry
Chul-Hyun Cho, Joung-Ho Moon, Ho-Kyoung Yoon, Seung-Gul Kang, Dongho Geum, Gi-Hoon Son, Jong-Min Lim, Leen Kim, Eun-Il Lee, Heon-Jeong Lee
This study examined the link between circadian rhythm changes due to bright light exposure and subthreshold bipolarity. Molecular circadian rhythms, polysomnography, and actigraphy data were studied in 25 young, healthy male subjects, divided into high and low mood disorder questionnaire (MDQ) score groups. During the first 2 days of the study, the subjects were exposed to daily-living light (150 lux) for 4 hours before bedtime. Saliva and buccal cells were collected 5 times a day for 2 consecutive days. During the subsequent 5 days, the subjects were exposed to bright light (1,000 lux), and saliva and buccal cell samples were collected in the same way...
2016: Scientific Reports
Maristela Oliveira Poletini, Leonardo Vinicius Monteiro de Assis, Maria Nathalia Moraes, Ana Maria de Lauro Castrucci
Melanin production within melanocytes is regulated, among others, by estradiol, whose effects on melanogenesis are still not completely elucidated. Here we show that although 10(-7) M 17β-estradiol (E2) increased tyrosinase mRNA levels in B16-F10 malignant melanocytes, there was a transient decrease and abolishment of the temporal variation of melanin content. Both parameters were much higher in the malignant than in normal Melan-a cells. Considering that silencing clock machinery in human melanocytes increases melanogenesis, we investigated clock gene expression in those cell lines...
October 2016: Molecular and Cellular Biochemistry
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