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https://www.readbyqxmd.com/read/29784789/ck1%C3%AE-%C3%AE%C2%B5-protein-kinase-primes-the-per2-circadian-phosphoswitch
#1
Rajesh Narasimamurthy, Sabrina R Hunt, Yining Lu, Jean-Michel Fustin, Hitoshi Okamura, Carrie L Partch, Daniel B Forger, Jae Kyoung Kim, David M Virshup
Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784786/two-ck1%C3%AE-transcripts-regulated-by-m6a-methylation-code-for-two-antagonistic-kinases-in-the-control-of-the-circadian-clock
#2
Jean-Michel Fustin, Rika Kojima, Kakeru Itoh, Hsin-Yi Chang, Ye Shiqi, Bowen Zhuang, Asami Oji, Shingo Gibo, Rajesh Narasimamurthy, David Virshup, Gen Kurosawa, Masao Doi, Ichiro Manabe, Yasushi Ishihama, Masahito Ikawa, Hitoshi Okamura
The N 6 -methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA ( Ck1δ ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29770483/melatonin-modulates-dysregulated-circadian-clocks-in-mice-with-diethylnitrosamine-induced-hepatocellular-carcinoma
#3
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29767668/genetic-variations-in-circadian-rhythm-genes-and-susceptibility-for-myocardial-infarction
#4
Ivana Škrlec, Jakov Milic, Marija Heffer, Borut Peterlin, Jasenka Wagner
Disruption of endogenous circadian rhythms has been shown to increase the risk of developing myocardial infarction (MI), suggesting that circadian genes might play a role in determining disease susceptibility. We conducted a case-control study on 200 patients hospitalized due to MI and 200 healthy controls, investigating the association between MI and single nucleotide polymorphisms (SNPs) in four circadian genes (ARNTL, CLOCK, CRY2, and PER2). The variants of all four genes were chosen based on their previously reported association with cardiovascular risk factors, which have a major influence on the occurrence of myocardial infarction...
May 14, 2018: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29765408/the-interaction-between-bmal1-and-per2-in-mouse-bmsc-osteogenic-differentiation
#5
Haiya Zhuo, Yuhong Wang, Qing Zhao
The circadian clock is a system that controls endogenous time of organisms, and it regulates the physiology and behavior of bodies. The transcription factors Brain and Muscle ARNT-like Protein 1 (BMAL1) and Period2 (Per2) are components of the circadian clock, and they play vital roles in circadian clock function. Both Bmal1-/- mice and Per2-/- mice display obvious bone volume changes. In this study, we inhibited the expression of Bmal1 in bone marrow-derived mesenchymal stem cells (BMSCs) using a lentiviral vector harboring RNAi sequences, which increased the osteogenic differentiation capability of BMSCs...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29761750/obesity-disrupts-rhythmic-clock-gene-expression-in-maternal-adipose-tissue-during-rat-pregnancy
#6
Rachael C Crew, Peter J Mark, Brendan J Waddell
Obesity during pregnancy causes numerous maternal and fetal health complications, but the underlying mechanisms remain unclear. Adipose tissue dysfunction in obesity has previously been linked to disruption of the intrinsic adipose clock gene network that is crucial for normal metabolic function. This adipose clock also undergoes major change as part of the maternal metabolic adaptation to pregnancy, but whether this is affected by maternal obesity is unknown. Consequently, in this study we tested the hypothesis that obesity disturbs rhythmic gene expression in maternal adipose tissue across pregnancy...
June 2018: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/29760682/daily-gene-expression-rhythms-in-rat-white-adipose-tissue-do-not-differ-between-subcutaneous-and-intra-abdominal-depots
#7
Rianne van der Spek, Eric Fliers, Susanne E la Fleur, Andries Kalsbeek
White adipose tissue (WAT) is present in different depots throughout the body. Although all depots are exposed to systemic humoral signals, they are not functionally identical. Studies in clock gene knockout animals and in shift workers suggest that daily rhythmicity may play an important role in lipid metabolism. Differences in rhythmicity between fat depots might explain differences in depot function; therefore, we measured mRNA expression of clock genes and metabolic genes on a 3-h interval over a 24-h period in the subcutaneous inguinal depot and in the intra-abdominal perirenal, epididymal, and mesenteric depots of male Wistar rats...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29760192/circadian-rhythms-influence-the-severity-of-sepsis-in-mice-via-a-tlr2-dependent-leukocyte-intrinsic-mechanism
#8
Erica L Heipertz, Jourdan Harper, Charlie A Lopez, Erol Fikrig, Michael E Hughes, Wendy E Walker
Circadian rhythms coordinate an organism's activities and biological processes to the optimal time in the 24-h daylight cycle. We previously demonstrated that male C57BL/6 mice develop sepsis more rapidly when the disease is induced in the nighttime versus the daytime. In this report, we elucidate the mechanism of this diurnal difference. Sepsis was induced via cecal ligation and puncture (CLP) at zeitgeber time (ZT)-19 (2 am) or ZT-7 (2 pm). Like the males used in our prior study, female C57BL/6 mice had a worse outcome when CLP was induced at ZT-19 versus ZT-7, and these effects persisted when we pooled the data from both sexes...
May 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29755411/time-of-day-effects-on-metabolic-and-clock-related-adjustments-to-cold
#9
Frederico Sander Mansur Machado, Zhi Zhang, Yan Su, Paul de Goede, Remi Jansen, Ewout Foppen, Cândido Celso Coimbra, Andries Kalsbeek
Background: Daily cyclic changes in environmental conditions are key signals for anticipatory and adaptive adjustments of most living species, including mammals. Lower ambient temperature stimulates the thermogenic activity of brown adipose tissue (BAT) and skeletal muscle. Given that the molecular components of the endogenous biological clock interact with thermal and metabolic mechanisms directly involved in the defense of body temperature, the present study evaluated the differential homeostatic responses to a cold stimulus at distinct time-windows of the light/dark-cycle...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29749758/the-role-of-mir-92b-in-cholangiocarcinoma-patients
#10
Min-Hang Zhou, Hong-Wei Zhou, Mo Liu, Jun-Zhong Sun
PURPOSE: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. METHODS: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan-Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery...
April 1, 2018: International Journal of Biological Markers
https://www.readbyqxmd.com/read/29746958/hippocampal-microrna-mrna-regulatory-network-is-affected-by-physical-exercise
#11
Jansen Fernandes, Andre Schwambach Vieira, Juliana Carlota Kramer-Soares, Eduardo Alves Da Silva, Kil Sun Lee, Iscia Lopes-Cendes, Ricardo Mario Arida
BACKGROUND: It is widely known that physical activity positively affects the overall health and brain function. Recently, microRNAs (miRNAs) have emerged as potential regulators of numerous biological processes within the brain. These molecules modulate gene expression post-transcriptionally by inducing mRNA degradation and inhibiting the translation of target mRNAs. METHODS: To verify whether the procognitive effects of physical exercise are accompanied by changes in the activity of miRNA-mRNA network in the brain, differential expression analysis was performed in the hippocampus of control (CTL) and exercised (Ex) rats subjected to 4 weeks of treadmill exercise...
May 7, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29686649/a-free-choice-high-fat-high-sugar-diet-alters-day-night-per2-gene-expression-in-reward-related-brain-areas-in-rats
#12
Aurea Susana Blancas-Velazquez, Unga A Unmehopa, Leslie Eggels, Laura Koekkoek, Andries Kalsbeek, Jorge Mendoza, Susanne E la Fleur
Under normal light-dark conditions, nocturnal rodents consume most of their food during the dark period. Diets high in fat and sugar, however, may affect the day-night feeding rhythm resulting in a higher light phase intake. In vitro and in vivo studies showed that nutrients affect clock-gene expression. We therefore hypothesized that overconsuming fat and sugar alters clock-gene expression in brain structures important for feeding behavior. We determined the effects of a free-choice high-fat high-sugar (fcHFHS) diet on clock-gene expression in rat brain areas related to feeding and reward and compared them with chow-fed rats...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29669984/circadian-rhythms-of-micturition-during-jet-lag
#13
Kakeru Ito, Miho Yasuda, Yuki Maeda, Jean-Michel Fustin, Yoshiaki Yamaguchi, Yuka Kono, Hiromitsu Negoro, Akihiro Kanematsu, Osamu Ogawa, Masao Doi, Hitoshi Okamura
Micturition behavior follows regular day/night fluctuations, and unwanted increase in micturition could occur during night in jet lag condition. To clarify the effect of jet lag on micturition behavior, we simultaneously detected circadian micturition patterns and locomotor activity rhythms of mice under experimental jet lag conditions, by applying the improved automated Voided Stain on Paper (aVSOP) method. When wild-type (WT) mice were phase-advanced for 8 hours, day-night variation of micturition was disrupted suddenly, and this irregular daily micturition continued until 8 days, although their activity rhythms entrained gradually day by day until 8 days...
2018: Biomedical Research
https://www.readbyqxmd.com/read/29626648/abnormal-circadian-locomotor-rhythms-and-per-gene-expression-in-six-month-old-triple-transgenic-mice-model-of-alzheimer-s-disease
#14
Meina Wu, Fang Zhou, Xiuli Cao, Junting Yang, Yu Bai, Xudong Yan, Jimin Cao, Jinshun Qi
Circadian rhythm disturbance (CRD) is one of the iconic manifestations in Alzheimer's disease (AD), a disease tightly associated with age, but the characteristics and gender difference of CRD occurred in AD have not been well demonstrated. Using 6-month-old triple transgenic AD mouse model (3xTg-AD) without obvious brain pathological changes, we demonstrated the gender difference of CRD at this age. We further showed abnormal Per gene expression in the central clock suprachiasmatic nucleus (SCN) of the 3xTg-AD mice...
April 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29610316/long-term-in-vivo-recording-of-circadian-rhythms-in-brains-of-freely-moving-mice
#15
Long Mei, Yanyan Fan, Xiaohua Lv, David K Welsh, Cheng Zhan, Eric Erquan Zhang
Endogenous circadian clocks control 24-h physiological and behavioral rhythms in mammals. Here, we report a real-time in vivo fluorescence recording system that enables long-term monitoring of circadian rhythms in the brains of freely moving mice. With a designed reporter of circadian clock gene expression, we tracked robust Cry1 transcription reporter rhythms in the suprachiasmatic nucleus (SCN) of WT, Cry1 -/- , and Cry2 -/- mice in LD (12 h light, 12 h dark) and DD (constant darkness) conditions and verified that signals remained stable for over 6 mo...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29605504/circadian-genes-period1b-and-period2-differentially-regulate-inflammatory-responses-in-zebrafish
#16
Da-Long Ren, Jun-Long Zhang, Lei-Qing Yang, Xiao-Bo Wang, Zong-Yi Wang, Deng-Feng Huang, Chen Tian, Bing Hu
The circadian clock has been shown to regulate various immune processes in different animals. Our previous report demonstrated that the innate immune responses in zebrafish show significant rhythmicity that could be regulated by melatonin. Here, we used diurnal zebrafish to determine the role of circadian genes in the inflammatory responses. Our results indicate that circadian genes exhibit rhythmic oscillations in zebrafish leukocytes, and mutations of the clock genes period1b (per1b) and period2 (per2) considerably affect these oscillations...
March 29, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29593513/zebrafish-lacking-circadian-gene-per2-exhibit-visual-function-deficiency
#17
Deng-Feng Huang, Ming-Yong Wang, Wu Yin, Yu-Qian Ma, Han Wang, Tian Xue, Da-Long Ren, Bing Hu
The retina has an intrinsic circadian clock, but the importance of this clock for vision is unknown. Zebrafish offer many advantages for studying vertebrate vision and circadian rhythm. Here, we explored the role of zebrafish per2 , a light-regulated gene, in visual behavior and the underlying mechanisms. We observed that per2 mutant zebrafish larvae showed decreased contrast sensitivity and visual acuity using optokinetic response (OKR) assays. Using a visual motor response (VMR) assay, we observed normal OFF responses but abnormal ON responses in mutant zebrafish larvae...
2018: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29588368/clock-phosphorylation-by-akt-regulates-its-nuclear-accumulation-and-circadian-gene-expression-in-peripheral-tissues
#18
Amelia K Luciano, Wenping Zhou, Jeans M Santana, Cleo Kyriakides, Heino Velazquez, William C Sessa
Circadian locomotor output cycles kaput (CLOCK) is a transcription factor which activates transcription of clock-controlled genes (CCG) by heterodimerizing with BMAL1 and binding to E-box elements on DNA. While several phosphorylation sites on CLOCK have already been identified, this study characterizes a novel phosphorylation site at Serine 845 (S836 in humans). Here we show that CLOCK is a novel AKT substrate in vitro and in cells, and this phosphorylation site is a negative regulator of CLOCK nuclear localization by acting as a binding site for 14-3-3 proteins...
March 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29577261/clock-genes-alterations-and-endocrine-disorders
#19
REVIEW
Anna Angelousi, Eva Kassi, Narjes Nasiri-Ansari, Martin O Weickert, Harpal Randeva, Gregory Kaltsas
BACKGROUND: Various endocrine signals oscillate over the 24-hour period and so does the responsiveness of target tissues. These daily oscillations do not occur solely in response to external stimuli but are also under the control of an intrinsic circadian clock. DESIGN: We searched the PubMed database to identify studies describing the associations of clock genes with endocrine diseases. RESULTS: Various human single nucleotide polymorphisms of BMAL1 and CLOCK genes exhibited significant associations with type 2 diabetes mellitus...
March 25, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29570674/per-a-circadian-clock-component-mediates-the-suppression-of-mmp-1-expression-in-hacat-keratinocytes-by-camp
#20
Miji Yeom, HansongI Lee, Seoungwoo Shin, Deokhoon Park, Eunsun Jung
Skin circadian clock system responds to daily changes, thereby regulating skin functions. Exposure of the skin to UV irradiation induces the expression of matrix metalloproteinase-1 (MMP-1) and causes DNA damage. It has been reported both DNA repair and DNA replication are regulated by the circadian clock in mouse skin. However, the molecular link between circadian clock and MMP-1 has little been investigated. We found PERIOD protein, a morning clock component, represses the expression of MMP-1 in human keratinocytes by using a PER-knockdown strategy...
March 23, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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