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https://www.readbyqxmd.com/read/28545154/site-specific-phosphorylation-of-casein-kinase-1-%C3%AE-ck1%C3%AE-regulates-its-activity-towards-the-circadian-regulator-per2
#1
Gracie Wee Ling Eng, Edison, David M Virshup
Circadian rhythms are intrinsic ~24 hour cycles that regulate diverse aspects of physiology, and in turn are regulated by interactions with the external environment. Casein kinase 1 delta (CK1δ, CSNK1D) is a key regulator of the clock, phosphorylating both stabilizing and destabilizing sites on the PER2 protein, in a mechanism known as the phosphoswitch. CK1δ can itself be regulated by phosphorylation on its regulatory domain, but the specific sites involved, and the role this plays in control of circadian rhythms as well as other CK1-dependent processes is not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28535015/the-circadian-clock-gene-per2-plays-an-important-role-in-tumor-suppression-through-regulating-tumor-associated-genes-in-human-oral-squamous-cell-carcinoma
#2
Xiaoli Su, Dan Chen, Kai Yang, Qin Zhao, Dan Zhao, Xiaoqiang Lv, Yiran Ao
Low expression of the clock gene PER2 is closely related to carcinogenesis and the development of cancer; however, the mechanism of the low expression of PER2 that led to cell malignant transformation remains unclear. This study used RNA interference (RNAi) technology to silence PER2 in SCC15 human oral squamous cell carcinoma (OSCC) cells. Then it was found that the ability of cancer cell proliferation, migration, and invasion were markedly increased (P<0.05), and the ability of cancer cell apoptosis and the number of cells in G1/G0 phase were markedly reduced (P<0...
May 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#3
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/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/28506121/mammalian-circadian-period-but-not-phase-and-amplitude-is-robust-against-redox-and-metabolic-perturbations
#5
Marrit Putker, Priya Crosby, Kevin A Feeney, Nathaniel P Hoyle, Ana S H da Costa, Edoardo Gaude, Christian Frezza, John Stuart O'Neill
AIMS: Circadian rhythms permeate all levels of biology to temporally regulate cell and whole-body physiology, although the cell-autonomous mechanism that confers ~24-hour periodicity is incompletely understood. Reports describing circadian oscillations of over-oxidised peroxiredoxin abundance have suggested redox signaling plays an important role in the timekeeping mechanism. Here, we tested the functional contribution that redox state and primary metabolism make to mammalian cellular timekeeping...
May 15, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28498398/per2-is-downregulated-by-the-lps-induced-inflammatory-response-in-synoviocytes-in-rheumatoid-arthritis-and-is-implicated-in-disease-susceptibility
#6
Hwayoung Lee, Seong-Su Nah, Sung-Hae Chang, Hyung-Ki Kim, Jun-Tack Kwon, Sanghyun Lee, Ik-Hyun Cho, Sang Won Lee, Young Ock Kim, Seung-Jae Hong, Hak-Jae Kim
The clinical symptoms of rheumatoid arthritis (RA) present with circadian variation, with joint stiffness and pain more prominent in the early morning. The mammalian clock genes, which include circadian locomotor output cycles kaput, brain and muscle Arnt-like protein 1, period and cryptochrome, regulate circadian rhythms. In order to identify the association between genetic polymorphisms in the circadian clock gene period 2 (PER2) and RA, the present study genotyped three PER2 single nucleotide polymorphisms (SNPs), rs934945, rs6754875, and rs2304674, using genetic information from 256 RA patients and 499 control subjects...
May 11, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28496429/molecular-mechanisms-regulating-temperature-compensation-of-the-circadian-clock
#7
REVIEW
Rajesh Narasimamurthy, David M Virshup
An approximately 24-h biological timekeeping mechanism called the circadian clock is present in virtually all light-sensitive organisms from cyanobacteria to humans. The clock system regulates our sleep-wake cycle, feeding-fasting, hormonal secretion, body temperature, and many other physiological functions. Signals from the master circadian oscillator entrain peripheral clocks using a variety of neural and hormonal signals. Even centrally controlled internal temperature fluctuations can entrain the peripheral circadian clocks...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28487473/epigenetic-regulation-of-the-circadian-clock-role-of-5-aza-2-deoxycytidine
#8
Yoshiaki Onishi, Tatsunosuke Tomita, Ryoji Kurita
We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypo-methylated, respectively and that 5-aza-2'-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 hours in RPMI8402 cells...
May 9, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28486525/hypothesis-driven-single-cell-dual-oscillator-mathematical-model-of-circadian-rhythms
#9
Shiju S, K Sriram
Molecular mechanisms responsible for 24 h circadian oscillations, entrainment to external cues, encoding of day length and the time-of-day effects have been well studied experimentally. However, it is still debated from the molecular network point of view whether each cell in suprachiasmatic nuclei harbors two molecular oscillators, where one tracks dawn and the other tracks dusk activities. A single cell dual morning and evening oscillator was proposed by Daan et al., based on the molecular network that has two sets of similar non-redundant per1/cry1 and per2/cry2 circadian genes and each can independently maintain their endogenous oscillations...
2017: PloS One
https://www.readbyqxmd.com/read/28484984/the-central-clock-controls-the-daily-rhythm-of-aqp5-expression-in-salivary-glands
#10
Hitoshi Uchida, Takahiro J Nakamura, Nana N Takasu, Aya Obana-Koshino, Hitomi Ono, Takeshi Todo, Takayoshi Sakai, Wataru Nakamura
Salivary secretion displays day-night variations that are controlled by the circadian clock. The central clock in the suprachiasmatic nucleus (SCN) regulates daily physiological rhythms by prompting peripheral oscillators to adjust to changing environments. Aquaporin 5 (Aqp5) is known to play a key role in salivary secretion, but the association between Aqp5 and the circadian rhythm is poorly understood. The aim of our study was to evaluate whether Aqp5 expression in submandibular glands (SMGs) is driven by the central clock in the SCN or by autonomous oscillations...
May 8, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28469105/long-term-levodopa-treatment-accelerates-the-circadian-rhythm-dysfunction-in-a-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#11
Si-Yue Li, Ya-Li Wang, Wen-Wen Liu, Dong-Jun Lyu, Fen Wang, Cheng-Jie Mao, Ya-Ping Yang, Li-Fang Hu, Chun-Feng Liu
BACKGROUND: Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD. METHODS: The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days...
May 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28466226/analysis-of-dna-damage-response-to-ionizing-radiation-in-serum-shock-synchronized-human-fibroblasts
#12
Samantha Corrà, Riccardo Salvadori, Leonardo Bee, Vito Barbieri, Maddalena Mognato
Many aspects of cellular physiology, including cellular response to genotoxic stress, are related to the circadian rhythmicity induced by the molecular clock. The current study investigated if the cellular response to DNA damage is in relation to endogenous expression levels of the PER2 protein, a key component of the molecular regulatory system that confers rhythmicity in mammalian cells. Human normal fibroblasts (CCD-34Lu) were subjected to serum shock to induce circadian oscillations of the PER2 protein and then irradiated with γ- rays at times corresponding to the trough and peak expression of the PER2 protein...
May 3, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28461004/disruption-of-normal-circadian-clock-function-in-a-mouse-model-of-tauopathy
#13
Korey Stevanovic, Amara Yunus, Aurelie Joly-Amado, Marcia Gordon, David Morgan, Danielle Gulick, Joshua Gamsby
Disruption of normal circadian rhythm physiology is associated with neurodegenerative disease, which can lead to symptoms such as altered sleep cycles. In Alzheimer's disease (AD), circadian dysfunction has been attributed to β-amyloidosis. However, it is unclear whether tauopathy, another AD-associated neuropathology, can disrupt the circadian clock. We have evaluated the status of the circadian clock in a mouse model of tauopathy (Tg4510). Tg4510 mice display a long free-running period at an age when tauopathy is present, and show evidence of tauopathy in the suprachiasmatic nucleus (SCN) of the hypothalamus - the site of the master circadian clock...
April 28, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28460049/tumor-necrosis-factor-alpha-tnf-%C3%AE-disrupts-kir4-1-channel-expression-resulting-in-m%C3%A3-ller-cell-dysfunction-in-the-retina
#14
Iraj Hassan, Qianyi Luo, Sreeparna Majumdar, James M Dominguez, Julia V Busik, Ashay D Bhatwadekar
Purpose: Diabetic patients often are affected by vision problems. We previously identified diabetic retinopathy (DR) as a disease of clock gene dysregulation. TNF-α, a proinflammatory cytokine, is known to be elevated in DR. Müller cells maintain retinal water homeostasis and K+ concentration via Kir4.1 channels. Notably, Kir4.1 expression is reduced in diabetes; however, the interplay of TNF-α, Kir4.1, and clock genes in Müller cells remains unknown. We hypothesize that the Kir4...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28452286/clock-gene-expression-in-the-suprachiasmatic-nucleus-of-hibernating-arctic-ground-squirrels
#15
Tomoko Ikeno, Cory T Williams, C Loren Buck, Brian M Barnes, Lily Yan
Most organisms have a circadian system, entrained to daily light-dark cycles, that regulates 24-h rhythms of physiology and behavior. It is unclear, however, how circadian systems function in animals that exhibit seasonal metabolic suppression, particularly when this coincides with the long-term absence of a day-night cycle. The arctic ground squirrel, Urocytellus parryii, is a medium-sized, semi-fossorial rodent that appears above-ground daily during its short active season in spring and summer before re-entering a constantly dark burrow for 6 to 9 months of hibernation...
April 1, 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28448534/intense-light-elicited-upregulation-of-mir-21-facilitates-glycolysis-and-cardioprotection-through-per2-dependent-mechanisms
#16
Colleen Marie Bartman, Yoshimasa Oyama, Kelley Brodsky, Ludmila Khailova, Lori Walker, Michael Koeppen, Tobias Eckle
A wide search for ischemic preconditioning (IPC) mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2) to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28439257/high-resolution-recording-of-the-circadian-oscillator-in-primary-mouse-%C3%AE-and-%C3%AE-cell-culture
#17
Volodymyr Petrenko, Yvan Gosmain, Charna Dibner
Circadian clocks have been developed in evolution as an anticipatory mechanism allowing for adaptation to the constantly changing light environment due to rotation of the Earth. This mechanism is functional in all light-sensitive organisms. There is a considerable body of evidence on the tight connection between the circadian clock and most aspects of physiology and metabolism. Clocks, operative in the pancreatic islets, have caught particular attention in the last years due to recent reports on their critical roles in regulation of insulin secretion and etiology of type 2 diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28427145/uncoupling-genotoxic-stress-responses-from-circadian-control-increases-susceptibility-to-mammary-carcinogenesis
#18
Mingzhu Fang, Pamela A Ohman Strickland, Hwan-Goo Kang, Helmut Zarbl
We previously demonstrated that chemopreventive methylselenocysteine (MSC) prevents N-Nitroso-N-methylurea (NMU)-induced mammary carcinogenesis in the susceptible Fischer 344 (F344) rats by enhancing NAD+-dependent SIRT1 activity, restoring circadian expression of Period 2 (Per2) and circadian controlled genes. Here, we show that compared to the genetically resistant Copenhagen (COP) rat strain, mammary glands of the F344 rats have a 4-hour phase delay in circadian expression of Per2. Consequently, F344 rats failed to increase SIRT1 activity and circadian expression of Per2 and DDRR genes after exposure to NMU...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423013/mapping-the-co-localization-of-the-circadian-proteins-per2-and-bmal1-with-enkephalin-and-substance-p-throughout-the-rodent-forebrain
#19
Ariana Frederick, Jory Goldsmith, Nuria de Zavalia, Shimon Amir
Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain...
2017: PloS One
https://www.readbyqxmd.com/read/28422445/transcriptional-profiling-of-shr-ncrl-prefrontal-cortex-reveals-hyperactivity-associated-genes-responsive-to-amphetamine-challenge
#20
Irene Joy I Dela Peña, Ike Dela Peña, June Bryan de la Peña, Hee Jin Kim, Aeree Sohn, Chan Young Shin, Doug Hyun Han, Bung-Nyun Kim, Jong Hoon Ryu, Jae Hoon Cheong
Several studies suggest a strong genetic component of attention-deficit/hyperactivity disorder (ADHD), a complex neurodevelopmental disorder characterized by inappropriate levels of hyperactivity, impulsivity, and inattention. Determining specific genetic risk variants for each symptom dimension of ADHD may aid in the identification of the biological risk factors of the disorder. In this study, we explored the potential genetic underpinnings of the hyperactive phenotype of ADHD. To this end, we examined differentially expressed genes (DEGs) in the prefrontal cortex (PFC) of SHR/NCrl, an animal model of ADHD, compared with its genetic control, the Wistar Kyoto (WKY/NCrl) rat and the Wistar rat, strain used to represent the "normal" heterogeneous population...
April 19, 2017: Genes, Brain, and Behavior
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