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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
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
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
Joseph F O'Grady, Laura S Hoelters, Martin T Swain, David C Wilcockson
BACKGROUND: Talitrus saltator is an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean. T. saltator exhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species...
2016: PeerJ
Huan Wang, Hui Chen
OBJECTIVE: Circadian rhythm disruption is shown to be the cause of various health disorders. CLOCK and BMAL1, two core circadian transcription factors, were associated with the regulation of glucose homeostasis. This study evaluated the association between single nucleotide polymorphisms in CLOCK and BMAL1 gene and insulin resistance (IR) in hypertensive patients. DESIGN AND METHOD: We collected 334 outpatients with essential hypertension (EH), who have not taken any antihypertensive agents or stopped the medications for at least a week for this case-control study...
September 2016: Journal of Hypertension
Chang-Sheng Sheng, Yi-Bang Cheng, Fang-Fei Wei, Wen-Yi Yang, Qian-Hui Guo, Fei-Ka Li, Qi-Fang Huang, Lutgarde Thijs, Yan Li, Jan A Staessen, Ji-Guang Wang
OBJECTIVE: No previous study addressed the relative contributions of environmental and genetic cues to the diurnal blood pressure rhythmicity. We firstly investigated the explained variance of environmental and clock genes in relation to the night-to-day ratio (NDR) and morning surge (MS), respectively. DESIGN AND METHOD: From 24-h ambulatory recordings of systolic blood pressure (SBP) obtained in untreated Chinese patients (51% women; mean age, 51 years), we computed NDR in 897 and MS in 637...
September 2016: Journal of Hypertension
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...
2016: Skeletal Muscle
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
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
Xiaoyue Pan, Christopher A Bradfield, M Mahmood Hussain
Circadian rhythms controlled by clock genes affect plasma lipids. Here we show that global ablation of Bmal1 in Apoe(-/-) and Ldlr(-/-) mice and its liver-specific ablation in Apoe(-/-) (L-Bmal1(-/-)Apoe(-/-)) mice increases, whereas overexpression of BMAL1 in L-Bmal1(-/-)Apoe(-/-) and Apoe(-/-)mice decreases hyperlipidaemia and atherosclerosis. Bmal1 deficiency augments hepatic lipoprotein secretion and diminishes cholesterol excretion to the bile. Further, Bmal1 deficiency reduces expression of Shp and Gata4...
October 10, 2016: Nature Communications
Dalei Wu, Fraydoon Rastinejad
The mammalian basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) transcription factors share common architectural features that include a bHLH DNA-binding domain and tandemly positioned PAS domains. The sixteen members of this family include the hypoxia-inducible factors (HIF-1α and HIF-2α), ARNT (also known as HIF-1β), CLOCK and BMAL1. Most bHLH-PAS proteins have been genetically linked to variety of diseases in humans, including cancers, metabolic syndromes and psychiatric conditions. To function as transcription factors, the bHLH-PAS proteins must form heterodimeric complexes...
October 6, 2016: Current Opinion in Structural Biology
Xiaoguang Li, Na Liu, Yizhu Wang, Jinglong Liu, Haigang Shi, Zhenzhen Qu, Tingting Du, Bin Guo, Bin Gu
Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while β-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3β (GSK-3β) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs...
October 4, 2016: Molecular and Cellular Endocrinology
Erica L Schoeller, Daniel D Clark, Sandeepa Dey, Nathan V Cao, Sheila J Semaan, Ling W Chao, Alexander S Kauffman, Lisa Stowers, Pamela L Mellon
Circadian rhythms synchronize physiological processes with the light-dark cycle and are regulated by a hierarchical system initiated in the suprachiasmatic nucleus (SCN), a hypothalamic region that receives direct photic input. The SCN then entrains additional oscillators in the periphery. Circadian rhythms are maintained by a molecular transcriptional feedback loop, of which BMAL1 is a key member. Disruption of circadian rhythms by deletion of the BMAL1 gene (Bmal1 KO) induces a variety of disease states, including infertility in males, due to unidentified mechanisms...
October 5, 2016: Endocrinology
Rebecca Dumbell, Alexei Leliavski, Olga Matveeva, Christopher Blaum, Anthony H Tsang, Henrik Oster
The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component BMAL1 leads to ablation of behavioural and physiological rhythms, hypocortisolism, impaired ACTH and behavioural stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context...
October 3, 2016: Endocrinology
Yi-Ying Chiou, Yanyan Yang, Naim Rashid, Rui Ye, Christopher P Selby, Aziz Sancar
The mammalian circadian clock is based on a transcription-translation feedback loop (TTFL) consolidated by secondary loops. In the primary TTFL, the circadian locomotor output cycles kaput (CLOCK)-brain and muscle Arnt-like protein-1 (BMAL1) heterodimer acts as the transcriptional activator, and Cryptochrome (CRY) and Period (PER) proteins function as repressors. PER represses by displacing CLOCK-BMAL1 from promoters in a CRY-dependent manner. Interestingly, genes with complex promoters may either be repressed or de-repressed by PER, depending on the particular promoter regulatory elements...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Carlo Garufi, Elisa Giacomini, Angela Torsello, Isabella Sperduti, Elisa Melucci, Marcella Mottolese, Massimo Zeuli, Giuseppe Maria Ettorre, Teresa Ricciardi, Francesco Cognetti, Mauro Magnani, Annamaria Ruzzo
The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months...
September 26, 2016: Scientific Reports
Rodrigo Antonio Peliciari-Garcia, Rafael Maso Prévide, Maria Tereza Nunes, Martin Elliot Young
Triiodothyronine (T3) is an important modulator of cardiac metabolism and function, often through modulation of gene expression. The cardiomyocyte circadian clock is a transcriptionally based molecular mechanism capable of regulating cardiac processes, in part by modulating responsiveness of the heart to extra-cardiac stimuli/stresses in a time-of-day (TOD)-dependent manner. Although TOD-dependent oscillations in circulating levels of T3 (and its intermediates) have been established, oscillations in T3 sensitivity in the heart is unknown...
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
Chang-Sheng Sheng, Yi-Bang Cheng, Fang-Fei Wei, Wen-Yi Yang, Qian-Hui Guo, Fei-Ka Li, Qi-Fang Huang, Lutgarde Thijs, Yan Li, Jan A Staessen, Ji-Guang Wang
OBJECTIVE: No previous study addressed the relative contributions of environmental and genetic cues to the diurnal blood pressure rhythmicity. We firstly investigated the explained variance of environmental and clock genes in relation to the night-to-day ratio (NDR) and morning surge (MS), respectively. DESIGN AND METHOD: From 24-h ambulatory recordings of systolic blood pressure (SBP) obtained in untreated Chinese patients (51% women; mean age, 51 years), we computed NDR in 897 and MS in 637...
September 2016: Journal of Hypertension
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