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Yiran Ao, Qin Zhao, Kai Yang, Gang Zheng, Xiaoqing Lv, Xiaoli Su
Clock genes are the core of the circadian rhythms in the human body and are important in regulating normal physiological functions. To date, research has indicated that the clock gene, period circadian clock 2 ( PER2 ), is downregulated in numerous types of cancer, and that it is associated with cancer occurrence and progression via the regulation of various downstream cell cycle genes. However, it remains unclear whether the decreased expression of PER2 influences the expression of other clock genes in cancer cells...
April 2018: Oncology Letters
Ning Wei, Michelle L Gumz, Anita T Layton
Major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion are known to exhibit circadian oscillations. However, the underlying mechanisms that govern these variations have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the renal circadian clock, and coupled that model to an epithelial transport model of the proximal convoluted cell of the rat kidney. The activity of the Na$^+$-H$^+$ exchanger 3 (NHE3) is assumed to be regulated by changes in transcription of the NHE3 mRNA due to regulation by circadian clock proteins...
March 14, 2018: American Journal of Physiology. Renal Physiology
Ha Kyun Kim, Hyun Jung Kim, Jae Hyung Kim, Tae Hoon Kim, Sang Hag Lee
Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats...
2018: PloS One
Tim S Nawrot, Nelly D Saenen, Julie Schenk, Bram G Janssen, Valeria Motta, Letizia Tarantini, Bianca Cox, Wouter Lefebvre, Charlotte Vanpoucke, Cristina Maggioni, Valentina Bollati
In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5 ) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing...
March 7, 2018: Environment International
Asuka Mogi, Ryo Yomoda, Syunya Kimura, Chisato Tsushima, Jun Takouda, Miho Sawauchi, Tomoko Maekawa, Hidenobu Ohta, Satoshi Nishino, Masatake Kurita, Nariyasu Mano, Noriko Osumi, Takahiro Moriya
The mitotic activity of certain tissues in the body is closely associated with circadian clock function. However, the effects of growth factors on the molecular clockwork are not fully understood. Stimulation of neural stem cells (NSCs) with epidermal growth factor (EGF), a well-known mitogen, is known to cause synchronized cell cycle progression with a period of approximately 24 h, closely associated with the Per2 gene expression rhythm. Here, we examined the effects of EGF on the molecular clockwork of NSCs...
March 5, 2018: Neuroscience
Halina Binde Doria, Marianna Boia Ferreira, Silvia Daniele Rodrigues, Sze Mei Lo, Cinthia Eloise Domingues, Lia Sumie Nakao, Sandro Xavier de Campos, Ciro Alberto de Oliveira Ribeiro, Marco Antonio Ferreira Randi
The circadian clock is a key cellular timing system that coordinates physiology and behavior. Light is a key regulator of the clock mechanism via its activation of Per and Cry clock gene expression. Evidence points to a key role of reactive oxygen species (ROS) in resetting this process. In this context, the aim of the present study was to explore copper as a ROS generator, using an innovative approach investigating its effects on circadian timing. Liver and brain from Danio rerio specimens exposed to 0, 5, 25 and 45 μg/L copper concentrations were obtained...
February 27, 2018: Ecotoxicology and Environmental Safety
C M McQueen, E E Schmitt, T R Sarkar, J Elswood, R P Metz, D Earnest, M Rijnkels, W W Porter
The molecular clock plays key roles in daily physiological functions, development, and cancer. Period 2 (PER2) is a repressive element, which inhibits transcription activated by positive clock elements, resulting in diurnal cycling of genes. However, there are gaps in our understanding of the role of the clock in normal development outside of its time keeping function. Here we show that PER2 has a non-circadian function that is critical to mammary gland development. Virgin Per2 deficient mice, Per2 -/- , have underdeveloped glands containing fewer bifurcations and terminal ducts...
February 28, 2018: Development
Jennifer Gile, Benjamin Scott, Tobias Eckle
OBJECTIVES: Delirium occurs in approximately 30% of critically ill patients, and the risk of dying during admission doubles in those patients. Molecular mechanisms causing delirium are largely unknown. However, critical illness and the ICU environment consistently disrupt circadian rhythms, and circadian disruptions are strongly associated with delirium. Exposure to benzodiazepines and constant light are suspected risk factors for the development of delirium. Thus, we tested the functional role of the circadian rhythm protein Period 2 (PER2) in different mouse models resembling delirium...
February 27, 2018: Critical Care Medicine
Yen-Sung Huang, Kuo-Cheng Lu, Tai-Kuang Chao, Jin-Shuen Chen, Ann Chen, Cheng-Yi Guo, Hsin-Yi Hsieh, Hsiu-Ming Shih, Huey-Kang Sytwu, Chia-Chao Wu
Membranous nephropathy (MN), a type of glomerular nephritis, is one of the most common causes of nephrotic syndrome in adults. Although it is known that melatonin plays a protective role in MN, the role of melatonin receptors in the pathophysiology of MN is unclear. Using an experimental MN model and clinical MN specimens, we studied melatonin receptor expression and found that melatonin receptor 1A (MTNR1A) expression was significantly downregulated in renal tubular epithelial cells. Molecular studies showed that the transcription factor pituitary homeobox-1 (PITX1) promoted MTNR1A expression via direct binding to its promoter...
February 26, 2018: Journal of Pineal Research
Leila M Guissoni Campos, Alessandre Hataka, Isis Z Vieira, Rogério L Buchaim, Isadora F Robalinho, Giovanna E P S Arantes, Joyce S Viégas, Henrique Bosso, Rafael M Bravos, Luciana Pinato
Oscillations of brain proteins in circadian rhythms are important for determining several cellular and physiological processes in anticipation of daily and seasonal environmental rhythms. In addition to the suprachiasmatic nucleus, the primary central oscillator, the cerebellum shows oscillations in gene and protein expression. The variety of local circuit rhythms that the cerebellar cortex contains influences functions such as motivational processes, regulation of feeding, food anticipation, language, and working memory...
2018: Frontiers in Physiology
Matheus Correa-Costa, David Gallo, Eva Csizmadia, Edward Gomperts, Judith-Lisa Lieberum, Carl J Hauser, Xingyue Ji, Binghe Wang, Niels Olsen Saraiva Câmara, Simon C Robson, Leo E Otterbein
Ischemia reperfusion injury (IRI) is the predominant tissue insult associated with organ transplantation. Treatment with carbon monoxide (CO) modulates the innate immune response associated with IRI and accelerates tissue recovery. The mechanism has been primarily descriptive and ascribed to the ability of CO to influence inflammation, cell death, and repair. In a model of bilateral kidney IRI in mice, we elucidate an intricate relationship between CO and purinergic signaling involving increased CD39 ectonucleotidase expression, decreased expression of Adora1, with concomitant increased expression of Adora2a/2b...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Simone Mocellin, Saveria Tropea, Clara Benna, Carlo Riccardo Rossi
BACKGROUND: Dysfunction of the circadian clock and single polymorphisms of some circadian genes have been linked to cancer susceptibility, although data are scarce and findings inconsistent. We aimed to investigate the association between circadian pathway genetic variation and risk of developing common cancers based on the findings of genome-wide association studies (GWASs). METHODS: Single nucleotide polymorphisms (SNPs) of 17 circadian genes reported by three GWAS meta-analyses dedicated to breast (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Consortium; cases, n = 15,748; controls, n = 18,084), prostate (Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium; cases, n = 14,160; controls, n = 12,724) and lung carcinoma (Transdisciplinary Research In Cancer of the Lung (TRICL) Consortium; cases, n = 12,160; controls, n = 16,838) in patients of European ancestry were utilized to perform pathway analysis by means of the adaptive rank truncated product (ARTP) method...
February 19, 2018: BMC Medicine
Dorjsuren Battogtokh, Shihoko Kojima, John J Tyson
In recent years, it has become increasingly apparent that antisense transcription plays an important role in the regulation of gene expression. The circadian clock is no exception: an antisense transcript of the mammalian core-clock gene PERIOD2 (PER2), which we shall refer to as Per2AS RNA, oscillates with a circadian period and a nearly 12 h phase shift from the peak expression of Per2 mRNA. In this paper, we ask whether Per2AS plays a regulatory role in the mammalian circadian clock by studying in silico the potential effects of interactions between Per2 and Per2AS RNAs on circadian rhythms...
February 15, 2018: PLoS Computational Biology
Matthew Stagl, Mary Bozsik, Christopher Karow, David Wertz, Ian Kloehn, Savin Pillai, Paul J Gasser, Marieke R Gilmartin, Jennifer A Evans
Glucocorticoid production is gated at the molecular level by the circadian clock in the adrenal gland. Stress influences daily rhythms in behavior and physiology, but it remains unclear how stress affects the function of the adrenal clock itself. Here, we examine the influence of stress on adrenal clock function by tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in vitro Relative to non-stressed controls, adrenals from stressed mice displayed marked changes in PER2::LUC rhythms. Interestingly, the effect of stress on adrenal rhythms varied by sex and the type of stress experienced in vivo To investigate the basis of sex differences in the adrenal response to stress, we next stimulated male and female adrenals in vitro with adrenocorticotropic hormone (ACTH)...
February 2018: Journal of Molecular Endocrinology
Sandra Korge, Bert Maier, Franziska Brüning, Lea Ehrhardt, Thomas Korte, Matthias Mann, Andreas Herrmann, Maria S Robles, Achim Kramer
Circadian clocks are molecular timekeeping mechanisms that allow organisms to anticipate daily changes in their environment. The fundamental cellular basis of these clocks is delayed negative feedback gene regulation with PERIOD and CRYPTOCHROME containing protein complexes as main inhibitory elements. For a correct circadian period, it is essential that such clock protein complexes accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly understood. We performed a systematic RNAi-mediated screen in human cells and identified 15 genes associated with the nucleo-cytoplasmic translocation machinery, whose expression is important for circadian clock dynamics...
January 2018: PLoS Genetics
Neha Agarwal, Ila Mishra, Sangeeta Rani, Vinod Kumar
We investigated if the duration and/or frequency of the light period affect 24-h rhythm of circadian clock genes in central and peripheral tissues of a non-photoperiodic songbird, the spotted munia (Lonchura punctulata), in which a circannual rhythm regulates the reproductive cycle. We monitored activity-rest pattern and measured 24-h mRNA oscillation of core clock (Bmal1, Clock, Per2, Cry1 and Cry2) and clock-controlled (E4bp4, Rorα and Rev-erbα) genes in the hypothalamus, retina, liver and gut of spotted munia subjected to an aberrant light-dark (LD) cycle (3...
January 25, 2018: Chronobiology International
I Herichová, K Hasáková, D Lukáčová, B Mravec, Ľ Horváthová, D Kavická
The effects of food reward on circadian system function were investigated in the hypothalamic nuclei, prefrontal cortex and liver. Food rewards of small hedonic and caloric value were provided for 16 days 3 h after light phase onset to male Wistar rats. The daily pattern of locomotor activity was monitored. Gene expression profiling performed in the dorsomedial hypothalamus (DMH) and liver at the time of reward delivery indicated transcriptional factors egr1 and npas2 as possible mediators of food reward effects...
December 30, 2017: Physiological Research
Atsushi Haraguchi, Miyabi Fukuzawa, Shiho Iwami, Yutaro Nishimura, Hiroaki Motohashi, Yu Tahara, Shigenobu Shibata
The circadian clock system is associated with feeding and mood. Patients with night eating syndrome (NES) delay their eating rhythm and their mood declines during the evening and night, manifesting as time-specific depression. Therefore, we hypothesized that the NES feeding pattern might cause time-specific depression. We established new NES model by restricted feeding with high-fat diet during the inactive period under normal-fat diet ad libitum. The FST (forced swimming test) immobility time in the NES model group was prolonged only after lights-on, corresponding to evening and early night for humans...
January 18, 2018: Scientific Reports
Heather Wei, Dominic Landgraf, George Wang, Michael J McCarthy
Most living organisms maintain cell autonomous circadian clocks that synchronize critical biological functions with daily environmental cycles. In mammals, the circadian clock is regulated by inputs from signaling pathways including glycogen synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on inositol metabolism. While it is suspected that lithium's inhibition of GSK3 causes rhythm changes, it is not known if inositol polyphosphates can also affect the circadian clock. We examined whether the signaling molecule inositol hexaphosphate (IP6) has effects on circadian rhythms...
January 10, 2018: Cellular Signalling
Leila Maria Guissoni Campos, Rogerio Leone Buchaim, Nathani Cristina da Silva, Caio Sergio Galina Spilla, Alessandre Hataka, Luciana Pinato
OBJECTIVE: The clock genes Period (per) 1 and 2 are essential components in the generation and adjustment of biological circadian rhythms by the suprachiasmatic nucleus (SCN). Both genes are also rhythmically present in extrahypothalamic areas such as the hippocampus and cerebellum, considered subordinate oscillators. Several pathological conditions alter rhythmic biological phenomena, but the mechanisms behind these changes involving the clock genes are not well defined. The current study investigated changes in PER1 and PER2 immunoreactivity in the SCN, hippocampus, and cerebellum in a neuroinflammation model...
January 5, 2018: Neuroimmunomodulation
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