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https://www.readbyqxmd.com/read/27913791/circadian-transcription-factor-bmal1-regulates-innate-immunity-against-select-rna-viruses
#1
Tanmay Majumdar, Jayeeta Dhar, Sonal Patel, Roman Kondratov, Sailen Barik
BMAL1 (brain and muscle ARNT-like protein 1, also known as MOP3 or ARNT3) belongs to the family of the basic helix-loop-helix (bHLH)-PAS domain-containing transcription factors, and is a key component of the molecular oscillator that generates circadian rhythms. Here, we report that BMAL1-deficient cells are significantly more susceptible to infection by two major respiratory viruses of the Paramyxoviridae family, namely RSV and PIV3. Embryonic fibroblasts from Bmal1(-/-) mice produced nearly 10-fold more progeny virus than their wild type controls...
December 1, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27906111/the-functional-significance-of-the-skeletal-muscle-clock-lessons-from-bmal1-knockout-models
#2
REVIEW
Stefano Schiaffino, Bert Blaauw, Kenneth A Dyar
The circadian oscillations of muscle genes are controlled either directly by the intrinsic muscle clock or by extrinsic factors, such as feeding, hormonal signals, or neural influences, which are in turn regulated by the central pacemaker, the suprachiasmatic nucleus of the hypothalamus. A unique feature of circadian rhythms in skeletal muscle is motor neuron-dependent contractile activity, which can affect the oscillation of a number of muscle genes independently of the muscle clock. The role of the intrinsic muscle clock has been investigated using different Bmal1 knockout (KO) models...
October 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#3
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27893733/adarb1-catalyzes-circadian-a-to-i-editing-and-regulates-rna-rhythm
#4
Hideki Terajima, Hikari Yoshitane, Haruka Ozaki, Yutaka Suzuki, Shigeki Shimba, Shinya Kuroda, Wataru Iwasaki, Yoshitaka Fukada
It has been proposed that the CLOCK-ARNTL (BMAL1) complex drives circadian transcription of thousands of genes, including Per and Cry family genes that encode suppressors of CLOCK-ARNTL-dependent transcription. However, recent studies demonstrated that 70-80% of circadian-oscillating mRNAs have no obvious rhythms in their de novo transcription, indicating the potential importance of post-transcriptional regulation. Our CLOCK-ChIP-seq analysis identified rhythmic expression of adenosine deaminase, RNA-specific, B1 (Adarb1, also known as Adar2), an adenosine-to-inosine (A-to-I) RNA-editing enzyme...
November 28, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#5
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27884645/dysregulated-circadian-rhythm-pathway-in-human-osteoarthritis-nr1d1-and-bmal1-suppression-alters-tgf-%C3%AE-signaling-in-chondrocytes
#6
Ryuichiro Akagi, Yorikazu Akatsu, Kathleen M Fisch, Oscar Alvarez-Garcia, Takeshi Teramura, Yuta Muramatsu, Masahiko Saito, Takahisa Sasho, Andrew I Su, Martin 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 21, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27884543/immunometabolism-is-it-under-the-eye-of-the-clock
#7
REVIEW
James O Early, Anne M Curtis
Molecular clocks allow an organism to track time of day, providing the means to anticipate and respond to the daily changes within the environment. In mammals the molecular clock consists of a network of proteins that form auto-regulatory feedback loops that drive rhythms in physiology and behavior. In recent times the extent to which the molecular clock controls key metabolic and immune pathways has begun to emerge. For example, the main clock protein BMAL1 has been linked to mitochondrial metabolism, mitochondrial dynamics and various host defense pathways...
November 21, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27883893/circadian-alterations-during-early-stages-of-alzheimer-s-disease-are-associated-with-aberrant-cycles-of-dna-methylation-in-bmal1
#8
Peter Cronin, Michael J McCarthy, Andrew S P Lim, David P Salmon, Douglas Galasko, Eliezer Masliah, Philip L De Jager, David A Bennett, Paula Desplats
INTRODUCTION: Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are incompletely understood. We hypothesized that aberrant DNA methylation may affect circadian rhythms in AD. METHODS: We investigated DNA methylation, transcription, and expression of BMAL1, a positive regulator of the circadian clock, in cultured fibroblasts and brain samples from two independent cohorts of aging and AD...
November 21, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27864077/trpv1-participates-in-the-activation-of-clock-molecular-machinery-in-the-brown-adipose-tissue-in-response-to-light-dark-cycle
#9
Maria Nathalia Moraes, Nathana Mezzalira, Leonardo Vinicius Monteiro de Assis, Michael Menaker, Ali Guler, Ana Maria L Castrucci
Transient receptor potential (TRPs) channels are involved in thermogenesis, and temperature and energy balance control. Mice lacking TrpV1 become more obese and develop insulin resistance when fed with high fat diet; however, a relationship between metabolic disorders, TRP channels, and clock genes is still unknown. Based on this, we hypothesized that TRPV1 channels would be involved in the synchronization of clock genes in the peripheral tissues. To address this question, we used wild type (WT) and TrpV1 knockout (KO) mice kept in constant darkness (DD) or in light-dark cycle (LD)...
November 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27857215/taurine-treatment-modulates-circadian-rhythms-in-mice-fed-a-high-fat-diet
#10
Ana Lucia C Figueroa, Hugo Figueiredo, Sandra A Rebuffat, Elaine Vieira, Ramon Gomis
Close ties have been made among certain nutrients, obesity, type 2 diabetes and circadian clocks. Among nutrients, taurine has been documented as being effective against obesity and type 2 diabetes. However, the impact of taurine on circadian clocks has not been elucidated. We investigated whether taurine can modulate or correct disturbances in daily rhythms caused by a high-fat diet in mice. Male C57BL/6 mice were divided in four groups: control (C), control + taurine (C+T), high-fat diet (HFD) and HFD + taurine (HFD+T)...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27824722/antioxidant-treatment-improves-cardiac-dysfunction-in-a-murine-model-of-premature-aging
#11
Bianca Hemmeryckx, Philipp Hohensinner, Melissa Swinnen, Ward Heggermont, Johann Wojta, Henri Roger Lijnen
Bmal1-(brain and muscle ARNT-like protein-1) deficient (Bmal1) mice prematurely age because of an increased reactive oxygen species (ROS) production. These mice also show a decline in cardiac function with age. We investigated whether an antioxidant treatment can ameliorate the declining cardiac function in prematurely aged Bmal1 mice. Male Bmal1 and wild-type (Bmal1) mice were exposed for 15 weeks to a high fat and high cholesterol diet with or without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL; 5 mmol/L; in drinking water during the last 10 weeks)...
November 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27821487/circadian-clock-gene-bmal1-inhibits-tumorigenesis-and-increases-paclitaxel-sensitivity-in-tongue-squamous-cell-carcinoma
#12
Qingming Tang, Bo Cheng, Mengru Xie, Yatao Chen, Jiajia Zhao, Xin Zhou, Lili Chen
Circadian clock genes regulate cancer development and chemotherapy susceptibility. Accordingly, chronotherapy based on circadian phenotypes might be applied to improve therapeutic efficacy. In this study, we investigated whether the circadian clock gene Bmal1 inhibited tumor development and increased paclitaxel sensitivity in tongue squamous cell carcinoma (TSCC). Bmal1 expression was downregulated and its rhythmic pattern of expression was affected in TSCC samples and cell lines. Ectopic Bmal1 inhibited cell proliferation, migration and invasion in vitro and tumor growth in mouse xenograft models of TSCC...
November 7, 2016: Cancer Research
https://www.readbyqxmd.com/read/27814361/clockwork-orange-enhances-period-mediated-rhythms-in-transcriptional-repression-by-antagonizing-e-box-binding-by-clock-cycle
#13
Jian Zhou, Wangjie Yu, Paul E Hardin
The Drosophila circadian oscillator controls daily rhythms in physiology, metabolism and behavior via transcriptional feedback loops. CLOCK-CYCLE (CLK-CYC) heterodimers initiate feedback loop function by binding E-box elements to activate per and tim transcription. PER-TIM heterodimers then accumulate, bind CLK-CYC to inhibit transcription, and are ultimately degraded to enable the next round of transcription. The timing of transcriptional events in this feedback loop coincide with, and are controlled by, rhythms in CLK-CYC binding to E-boxes...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27803791/effects-of-lycium-barbarum-polysaccharide-on-type-2-diabetes-mellitus-rats-by-regulating-biological-rhythms
#14
Rui Zhao, Xu Gao, Tao Zhang, Xing Li
OBJECTIVES: Type 2 diabetes mellitus (T2DM) is associated with circadian disruption. Our previous experimental results have showed that dietary Lycium barbarum. polysaccharide (LBP-4a) exhibited hypoglycemic and improving insulin resistance (IR) activities. This study was to explore the mechanisms of LBP-4a for improving hyperglycemia and IR by regulating biological rhythms in T2DM rats. MATERIALS AND METHODS: The rats of T2DM were prepared by the high-sucrose-fat diets and injection of streptozotocin (STZ)...
September 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/27796320/orexin-signaling-regulates-both-the-hippocampal-clock-and-the-circadian-oscillation-of-alzheimer-s-disease-risk-genes
#15
Zhixiong Ma, Weiliang Jiang, Eric Erquan Zhang
Alzheimer's disease (AD) is a circadian clock-related disease. However, it is not very clear whether pre-symptomatic AD leads to circadian disruption or whether malfunction of circadian rhythms exerts influence on development of AD. Here, we report a functional clock that exists in the hippocampus. This oscillator both receives input signals and maintains the cycling of the hippocampal Per2 gene. One of the potential inputs to the oscillator is orexin signaling, which can shorten the hippocampal clock period and thereby regulate the expression of clock-controlled-genes (CCGs)...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27791398/timing-of-glucocorticoid-administration-determines-severity-of-lipid-metabolism-and-behavioral-effects-in-rats
#16
Tao Wu, Jianguo Jiang, Luna Yang, Haifeng Li, Wanjing Zhang, Yangyang Chen, Binggong Zhao, Boda Kong, Ping Lu, Zhenzhen Zhao, Jiawei Zhu, Zhengwei Fu
Glucocorticoids (GCs) are a group of steroid hormones secreted by the adrenal glands in circadian cycles, and the dysregulation of GC signaling has been suggested to cause metabolic syndrome. Even though prolonged GC exposure is associated with serious side effects such as metabolic syndrome and central nervous system disorders, the use of GCs in anti-inflammatory and immunosuppressive therapies has been continuously rising. Meanwhile, the exact mechanisms by which GCs can influence the lipid metabolism as well as behavior and how they are affected by time remain unknown...
October 28, 2016: Chronobiology International
https://www.readbyqxmd.com/read/27782878/npas1-arnt-and-npas3-arnt-crystal-structures-implicate-the-bhlh-pas-family-as-multi-ligand-binding-transcription-factors
#17
Dalei Wu, Xiaoyu Su, Nalini Potluri, Youngchang Kim, Fraydoon Rastinejad
The neuronal PAS domain proteins NPAS1 and NPAS3 are members of the basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) family, and their genetic deficiencies are linked to a variety of human psychiatric disorders including schizophrenia, autism spectrum disorders and bipolar disease. NPAS1 and NPAS3 must each heterodimerize with the aryl hydrocarbon receptor nuclear translocator (ARNT), to form functional transcription complexes capable of DNA binding and gene regulation. Here we examined the crystal structures of multi-domain NPAS1-ARNT and NPAS3-ARNT-DNA complexes, discovering each to contain four putative ligand-binding pockets...
October 26, 2016: ELife
https://www.readbyqxmd.com/read/27773697/reciprocal-regulation-between-the-circadian-clock-and-hypoxia-signaling-at-the-genome-level-in-mammals
#18
Yaling Wu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, Haijiao Zhao, Peihao Chen, Xiangbing Qi, Eric Erquan Zhang
Circadian regulation is critically important in maintaining metabolic and physiological homeostasis. However, little is known about the possible influence of the clock on physiological abnormalities occurring under pathological conditions. Here, we report the discovery that hypoxia, a condition that causes catastrophic bodily damage, is gated by the circadian clock in vivo. Hypoxia signals conversely regulate the clock by slowing the circadian cycle and dampening the amplitude of oscillations in a dose-dependent manner...
October 14, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27773696/circadian-clock-interaction-with-hif1%C3%AE-mediates-oxygenic-metabolism-and-anaerobic-glycolysis-in-skeletal-muscle
#19
Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27771283/rhythmic-bdnf-and-trkb-expression-patterns-in-the-prefrontal-cortex-are-lost-in-aged-rats
#20
Cinthia D Coria-Lucero, Rebeca S Golini, Ivana T Ponce, Nicolas Deyurka, Ana C Anzulovich, Silvia M Delgado, Lorena S Navigatore-Fonzo
Aging brain undergoes several changes leading to a decline in cognitive functions. Memory and learning-related genes such as Creb, Bdnf and its receptor TrkB, are expressed in different brain regions including prefrontal cortex. Those genes' proteins regulate a wide range of functions such as synaptic plasticity and long-term potentiation. In this work, our objectives were: 1) to investigate whether Creb1, Bdnf and TrkB genes display endogenous circadian expression rhythms, in the prefrontal cortex of rats maintained under constant darkness conditions; 2) to study the synchronization of those temporal patterns to the local cellular clock and 3) to evaluate the aging consequences on both cognition-related genes and activating clock transcription factor, BMAL1, rhythms...
October 19, 2016: Brain Research
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