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Weinert H Weinert D Schurov I Maywood ES Hastings MH 《Chronobiology international》2001,18(3):559-565
The expression of circadian clock genes was investigated in the suprachiasmatic nuclei (SCN) of young adult and old laboratory mice. Samples were taken at two time points, which corresponded to the expected maximum (circadian time 7 [CT7]) or minimum (CT21) of mPer mRNA expression. Whereas the young mice had a stable and well-synchronized circadian activity/rest cycle, the rhythms of old animals were less stable and were phase advanced. The expression of mPer1 mRNA and mPer2 mRNA was rhythmic in both groups, with peak values at CT7. The levels of mClock and mCry1 mRNA were not different depending on the time of day and did not vary with age. In contrast, an age-dependent difference was found in the case of mPer2 (but not mPer1) mRNA expression, with the maximum at CT7 significantly lower in old mice. The decreased expression of mPer2 may be relevant for the observed differences in the overt activity rhythm of aged mice. (Chronobiology International, 18(3), 559-565, 2001) 相似文献
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Hofman MA 《Chronobiology international》2000,17(3):245-259
The suprachiasmatic nucleus (SCN) of the hypothalamus is implicated in the timing of a wide variety of circadian processes. Since the environmental light-dark cycle is the main zeitgeber for many of the rhythms, photic information may have a synchronizing effect on the endogenous clock of the SCN by inducing periodic changes in the biological activity of certain groups of neurons. By studying the brains obtained at autopsy of human subjects, marked diurnal oscillations were observed in the neuropeptide content of the SCN. Vasopressin, for example, one of the most abundant peptides in the human SCN, exhibited a diurnal rhythm, with low values at night and peak values during the early morning. However, with advancing age, these diurnal fluctuations deteriorated, leading to a disrupted cycle with a reduced amplitude in elderly people. These findings suggest that the synthesis of some peptides in the human SCN exhibits an endogenous circadian rhythmicity, and that the temporal organization of these rhythms becomes progressively disturbed in senescence. (Chronobiology International, 17(3), 245-259, 2000) 相似文献
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Yonghua Xu Xiangmin Wang Surong Jiang Chen Men Di Xu Yan Guo Jun Wu 《Cellular & molecular biology letters》2018,23(1):50
Background
Microcystins are waterborne environmental toxins that induce oxidative stress and cause injuries in the heart. On the other hand, many physiological processes, including antioxidant defense, are under precise control by the mammalian circadian clock.Results
In the present study, we evaluated the effect of microcystin-LR (MC-LR) on the rhythmic expression patterns of circadian and antioxidant genes in rat cardiomyocytes using the serum shock technique. We found that a non-toxic dose (10 μm) of MC-LR decreased the amplitudes of rhythmic patterns of clock genes, while it increased the expression levels of antioxidant genes.Conclusions
Our results indicate an influence of MC-LR on the circadian clock system and clock-controlled antioxidant genes, which will shed some light on the explanation of heart toxicity induced by MC-LR from the viewpoint of chronobiology.6.
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The mechanisms of circadian clock function in Arabidopsis rely on the complex relationships among core clock components. The current model of the Arabidopsis oscillator comprises a myriad of repressors but the mechanisms responsible for activation remain largely unknown. In our recent studies, we have demonstrated that the rhythms in H3 acetylation (H3ac) and H3K4 trimethylation (H3K4me3) are a key mechanism at the positive arm of the oscillator. H3K4me3 rhythmic accumulation is delayed compared to that of H3ac, which opens the possibility for separate roles for each mark. Indeed, the use of inhibitors that block H3K4me3 accumulation was concomitant with increased clock repressor binding, suggesting that H3K4me3 might control the timing from activation to repression. Plants mis-expressing the histone methyltransferase SET DOMAIN GROUP 2 (SDG2/ATXR3) displayed altered H3K4me3 accumulation, oscillator gene expression and clock repressor binding, suggesting that SDG2/ATXR3 is a key component contributing to proper circadian expression. 相似文献
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The luteinizing hormone surge regulates circadian clock gene expression in the chicken ovary 总被引:1,自引:0,他引:1
The molecular circadian clock mechanism is highly conserved between mammalian and avian species. Avian circadian timing is regulated at multiple oscillatory sites, including the retina, pineal, and hypothalamic suprachiasmatic nucleus (SCN). Based on the authors' previous studies on the rat ovary, it was hypothesized that ovarian clock timing is regulated by the luteinizing hormone (LH) surge. The authors used the chicken as a model to test this hypothesis, because the timing of the endogenous LH surge is accurately predicted from the time of oviposition. Therefore, tissues can be removed before and after the LH surge, allowing one to determine the effect of LH on specific clock genes. The authors first examined the 24-h expression patterns of the avian circadian clock genes of Bmal1, Cry1, and Per2 in primary oscillatory tissues (hypothalamus and pineal) as well as peripheral tissues (liver and ovary). Second, the authors determined changes in clock gene expression after the endogenous LH surge. Clock genes were rhythmically expressed in each tissue, but LH influenced expression of these clock genes only in the ovary. The data suggest that expression of ovarian circadian clock genes may be influenced by the LH surge in vivo and directly by LH in cultured granulosa cells. LH induced rhythmic expression of Per1 and Bmal1 in arrhythmic, cultured granulosa cells. Furthermore, LH altered the phase and amplitude of clock gene rhythms in serum-shocked granulosa cells. Thus, the LH surge may be a mechanistic link for communicating circadian timing information from the central pacemaker to the ovary. 相似文献
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Whether a clock that generates a circatidal rhythm shares the same elements as the circadian clock is not fully understood. The mangrove cricket, Apteronemobius asahinai, shows simultaneously two endogenous rhythms in its locomotor activity; the circatidal rhythm generates active and inactive phases, and the circadian rhythm modifies activity levels by suppressing the activity during subjective day. In the present study, we silenced Clock (Clk), a master gene of the circadian clock, in A. asahinai using RNAi to investigate the link between the circatidal and circadian clocks. The abundance of Clk mRNA in the crickets injected with double-stranded RNA of Clk (dsClk) was reduced to a half of that in control crickets. dsClk injection also reduced mRNA abundance of another circadian clock gene period (per) and weakened diel oscillation in per mRNA expression. Examination of the locomotor rhythms under constant conditions revealed that the circadian modification was disrupted after silencing Clk expression, but the circatidal rhythm remained unaffected. There were no significant changes in the free-running period of the circatidal rhythm between the controls and the crickets injected with dsClk. Our results reveal that Clk is essential for the circadian clock, but is not required for the circatidal clock. From these results we propose that the circatidal rhythm of A. asahinai is driven by a clock, the molecular components of which are distinct from that of the circadian clock. 相似文献
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In this review, we present evidence from human and animal studies to evaluate the hypothesis that sleep and circadian rhythms have direct impacts on energy metabolism, and represent important mechanisms underlying the major health epidemics of obesity and diabetes. The first part of this review will focus on studies that support the idea that sleep loss and obesity are "interacting epidemics." The second part will discuss recent evidence that the circadian clock system plays a fundamental role in energy metabolism at both the behavioral and molecular levels. These lines of research must be seen as in their infancy, but nevertheless, have provided a conceptual and experimental framework that potentially has great importance for understanding metabolic health and disease. 相似文献
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Background
The suprachiasmatic nucleus (SCN), the master circadian clock, is a heterogeneous oscillator network, yet displays a robust synchronization dynamics. Recent single-cell bioluminescent imaging revealed temporal gradients in circadian clock gene expression in the SCN ex vivo. However, due to technical difficulty in biological approaches to elucidate the entire network structure of the SCN, characteristics of the gradient, which we refer to as phase wave, remain unknown.Methodology/Principal Findings
We implemented new approaches, i.e., quantitative analysis and model simulation to characterize the phase waves in Per2::Luciferase clock reporter gene expression of the rat SCN slice. Our quantitative study demonstrated not only a high degree of synchronization between the neurons and regular occurrence of the phase wave propagation, but also a significant amount of phase fluctuations contained in the wave. In addition, our simulations based on local coupling model suggest that the intercellular coupling strength estimated by the model simulations is significantly higher than the critical value for generating the phase waves. Model simulations also suggest that heterogeneity of the SCN neurons is one of the main factors causing the phase wave fluctuations. Furthermore, robustness of the SCN network against dynamical noise and variation of the natural frequencies inherent in these neurons was quantitatively assessed.Conclusions/Significance
To our knowledge, this is the first quantitative evaluation of the phase wave and further characterization of the SCN neuronal network features generating the wave i.e., intercellular synchrony, phase fluctuation, strong local coupling, heterogeneous periodicity and robustness. Our present study provides an approach, which will lead to a comprehensive understanding of mechanistic and/or biological significance of the phase wave in the central circadian oscillatory system. 相似文献14.
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Cristina Cadenas Leonie van de Sandt Karolina Edlund Miriam Lohr Birte Hellwig Rosemarie Marchan 《Cell cycle (Georgetown, Tex.)》2014,13(20):3282-3291
Several studies suggest a link between circadian rhythm disturbances and tumorigenesis. However, the association between circadian clock genes and prognosis in breast cancer has not been systematically studied. Therefore, we examined the expression of 17 clock components in tumors from 766 node-negative breast cancer patients that were untreated in both neoadjuvant and adjuvant settings. In addition, their association with metastasis-free survival (MFS) and correlation to clinicopathological parameters were investigated. Aiming to estimate functionality of the clockwork, we studied clock gene expression relationships by correlation analysis. Higher expression of several clock genes (e.g., CLOCK, PER1, PER2, PER3, CRY2, NPAS2 and RORC) was found to be associated with longer MFS in univariate Cox regression analyses (HR<1 and FDR-adjusted P < 0.05). Stratification according to molecular subtype revealed prognostic relevance for PER1, PER3, CRY2 and NFIL3 in the ER+/HER2- subgroup, CLOCK and NPAS2 in the ER-/HER2- subtype, and ARNTL2 in HER2+ breast cancer. In the multivariate Cox model, only PER3 (HR = 0.66; P = 0.016) and RORC (HR = 0.42; P = 0.003) were found to be associated with survival outcome independent of established clinicopathological parameters. Pairwise correlations between functionally-related clock genes (e.g., PER2-PER3 and CRY2-PER3) were stronger in ER+, HER2- and low-grade carcinomas; whereas, weaker correlation coefficients were observed in ER- and HER2+ tumors, high-grade tumors and tumors that progressed to metastatic disease. In conclusion, loss of clock genes is associated with worse prognosis in breast cancer. Coordinated co-expression of clock genes, indicative of a functional circadian clock, is maintained in ER+, HER2-, low grade and non-metastasizing tumors but is compromised in more aggressive carcinomas. 相似文献
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Fumiaki Muguruma Shin G. Goto Hideharu Numata Sakiko Shiga 《Cell and tissue research》2010,340(3):497-507
We examined the effect of photoperiod on the expression of circadian clock genes period (per) and timeless (tim), using quantitative real-time polymerase chain reaction (PCR), and the effect of photoperiod on subcellular distribution
of PERIOD (PER), using immunocytochemistry, in the blow fly, Protophormia terraenovae. Under both short-day and long-day conditions, the mRNA levels of per and tim in the brain oscillated, and their peaks and troughs occurred around lights-off and lights-on, respectively. The oscillations
persisted even under constant darkness. In the large ventral lateral neurons (l-LNvs), small ventral lateral neurons (s-LNvs), dorsal lateral neurons (LNds), and medial dorsal neurons (DNms), the subcellular distribution of PER-immunoreactivity changed with time. The number of cells with PER-immunoreactivity
in the nucleus was highest 12 h after lights-off and lowest 12 h after lights-on, regardless of photoperiod, suggesting that
PER nuclear translocation entrains to photoperiod. When temporal changes in the nuclear localization of PER were compared,
the neurons could be classified into 2 groups: the l-LNvs were similar to the s-LNvs, and the LNds were similar to DNms. In LNds and DNms, decreasing rates of the number of cells with PER immunoreactivity in the nucleus per brain from the maximum were large
as compared with those in l-LNvs and s-LNvs under short-day conditions. These results suggest that photoperiodic information is reflected in the expression patterns
of circadian clock genes per and tim and in the subcellular distribution of PER. This observation suggests that the 2 different groups of clock neurons respond
to photoperiod in slightly different manners. 相似文献
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Pardini L Kaeffer B Trubuil A Bourreille A Galmiche JP 《Chronobiology international》2005,22(6):951-961
Biological clock components have been detected in many epithelial tissues of the digestive tract of mammals (oral mucosa, pancreas, and liver), suggesting the existence of peripheral circadian clocks that may be entrainable by food. Our aim was to investigate the expression of main peripheral clock genes in colonocytes of healthy humans and in human colon carcinoma cell lines. The presence of clock components was investigated in single intact colonic crypts isolated by chelation from the biopsies of 25 patients (free of any sign of colonic lesions) undergoing routine colonoscopy and in cell lines of human colon carcinoma (Caco2 and HT29 clone 19A). Per-1, per-2, and clock mRNA were detected by real-time RT-PCR. The three-dimensional distributions of PER-1, PER-2, CLOCK, and BMAL1 proteins were recorded along colonic crypts by immunofluorescent confocal imaging. We demonstrate the presence of per-1, per-2, and clock mRNA in samples prepared from colonic crypts of 5 patients and in all cell lines. We also demonstrate the presence of two circadian clock proteins, PER-1 and CLOCK, in human colonocytes on crypts isolated from 20 patients (15 patients for PER-1 and 6 for CLOCK) and in colon carcinoma cells. Establishing the presence of clock proteins in human colonic crypts is the first step toward the study of the regulation of the intestinal circadian clock by nutrients and feeding rhythms. 相似文献