Diurnal difference in CAR mRNA expression.
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ABSTRACT:
SUBMITTER: Kanno Y
PROVIDER: S-EPMC517509 | biostudies-literature | 2004 Aug
REPOSITORIES: biostudies-literature
Publications
Diurnal difference in CAR mRNA expression.
Kanno Yuichiro Y Otsuka Satoshi S Hiromasa Takuya T Nakahama Takayuki T Inouye Yoshio Y
Nuclear receptor 20040828 1
BACKGROUND: The constitutive androstane receptor (CAR, NR1I3) plays a key role in the transcriptional activation of genes that encode xenobiotic/steroid and drug metabolizing enzymes. RESULTS: The expression of CAR mRNA throughout the circadian rhythm is reported for the first time in phase with the clock gene Bmal1 and in antiphase with the clock-controlled gene Rev-erbalpha mRNAs, with a peak at Zeitgeber time (ZT) 20 and a trough at ZT8, and a peak/trough ratio of 2.0. The diurnal difference ...[more]
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Project description:DNA methyltransferase 3B (DNMT3B) is critically involved in de novo DNA methylation and genomic stability, while the regulatory mechanism in liver is largely unknown. We previously reported that diurnal variation occurs in the mRNA expression of Dnmt3b in adult mouse liver. The aim of this study was to determine the mechanism underlying the diurnal expression pattern. The highest level and the lowest level of Dnmt3b mRNA expression were confirmed to occur at dawn and in the afternoon, respectively, and the expression pattern of Dnmt3b closely coincided with that of Bmal1. Since the diurnal pattern of Dnmt3b mRNA expression developed at weaning and scheduled feeding to separate the feeding cycle from the light/dark cycle led to a phase-shift in the expression, it could be assumed that feeding plays a critical role as an entrainment signal. In liver-specific Bmal1 knockout (L-Bmal1 KO) mice, L-Bmal1 deficiency resulted in significantly higher levels of Dnmt3b at all measured time points, and the time when the expression was the lowest in wild-type mice was shifted to earlier. Investigation of global DNA methylation revealed a temporal decrease of 5-methyl-cytosine percentage in the genome of wild-type mice in late afternoon. By contrast, no such decrease in 5-methyl-cytosine percentage was detected in L-Bmal1 KO mice, suggesting that altered Dnmt3b expression affects the DNA methylation state. Taken together, the results suggest that the feeding and hepatic clockwork generated by the clock genes, including Bmal1, regulate the diurnal variation in Dnmt3b mRNA expression and the consequent dynamic changes in global DNA methylation.
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Project description:BackgroundTo address a critical gap for application of cancer chronotherapy of when would be the best time(s) for treating an individual cancer patient, we conducted a pilot study to characterize diurnal variations of gene expression in oral mucosal tissue, which is vulnerable to damage from cancer therapies.MethodsWe conducted RNA-seq assay on individual oral mucosal samples collected from 11 healthy volunteers every 4 hours (6 time points). Using a cosine-based method, we estimated the individual and average values of peak-time and amplitude for each gene. Correlations between gene expression peak-times and age was examined, adjusting for individual's sleep timing.ResultsAmong candidate gene pathways that are relevant to treatment response, 7 of 16 genes (PER3, CIART, TEF, PER1, PER2, CRY2, ARNTL) involved in circadian regulation and 1 of 118 genes (WEE1) involved in cell cycle regulation achieved p-value ≤ 0.1 and relative amplitude>0.1. The average peak times were approximately 10:15 for PER3, CIART and TEF, 10:45 for PER1, 13:00 for WEE1, PER2 and CRY2, and 19:30 for ARNTL. Ranges in peak times across individuals differed by gene (e.g., 8 hours for PER1; 16.7 hours for WEE1). Older people had later peak times for PER1 (r = 0.77, p = 0.03) and PER3 (r = 0.69, p-value = 0.06).ConclusionIn oral mucosa, expression of some genes relevant to treatment response displayed diurnal variation. These genes may be candidates for development of biomarkers for optimizing individual timing of cancer therapy using non-invasively collected oral mucosa.
| S-EPMC8231453 | biostudies-literature
Project description:IntroductionCortisol levels in adults show a sharp decrease from mid-morning to mid-afternoon. Most toddlers take afternoon naps, which is associated with a less mature diurnal pattern characterized by a midday plateau in cortisol secretion. Napping in preschoolers produces a robust cortisol awakening response (CAR), which may account for such maturational differences. This experimental study extends prior work by examining whether the presence and timing of the nap-dependent CAR influences the diurnal cortisol pattern in toddlers.MethodsToddlers (n = 28; 13 females; 30-36 months) followed a strict biphasic sleep schedule (≥ 12.5h time in bed; ≥ 90 min nap) for ≥ 3 days before each of four randomly ordered, in-home cortisol assessments. For each assessment, saliva samples were obtained at morning awakening, ∼ 09:30, pre-nap, 0, 15, 30, 45, 90, and 135 min post-nap awakening (verified with actigraphy), and ∼ 19:30. On one day, children napped at their scheduled time, and parents collected saliva samples. On another day, children missed their nap, and parents collected saliva samples at matched times. On two other days, children napped 4h (morning) and 7h (afternoon) after awakening in the morning, during which time researchers collected pre- and post-nap saliva samples. Saliva was assayed for cortisol (μg/dl).ResultsThree-level multilevel models were used to estimate the CAR and diurnal cortisol patterns in all four conditions. Compared to the no-nap condition (no observed CAR; b = -0.78, p = 0.65), we found a pronounced cortisol rise following the morning nap (b = 11.00, p < 0.001) and both afternoon naps whether samples were collected by parents (b = 5.19, p < 0.01) or experimenters (b = 4.97, p < 0.01). Napping in the morning resulted in the most robust post-nap cortisol rise (b = 10.21, p < 0.001). Diurnal patterns were analyzed using piecewise growth modeling that estimated linear coefficients for five separate periods throughout the day (corresponding to morning decline, noon decline, post-nap rise, post-nap decline, and evening decline). We observed a significant post-nap rise in cortisol values on the parent-collected afternoon nap (b = 3.41, p < 0.01) and the experimenter-collected morning nap (b = 7.50, p < 0.01) days as compared to the no-nap day (b = -0.17, p = 0.82). No other differences in diurnal profiles were observed between the parent-collected nap and no-nap conditions; however, toddlers had a steeper evening decline on the day of the morning nap compared to the parent-collected afternoon nap (b = 0.30, p < 0.05) and no-nap conditions (b = 0.27, p < 0.05).DiscussionThese well-controlled findings suggest that the presence and timing of daytime naps influence the pattern of diurnal cortisol secretion in toddlers. They also provide support for the hypothesis that napping is the primary state driving the immature midday plateau in cortisol secretion, which becomes more adult-like across childhood. Prior studies of the diurnal cortisol pattern have employed a cubic model, and therefore, have not detected all possible variations due to napping. Our experimental data have important methodological implications for researchers examining associations between the slope of the diurnal cortisol pattern and developmental outcomes, as well as those utilizing afternoon cortisol reactivity protocols in napping children.
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Project description:The study aimed to elucidate the transcriptional changes introduced by genetic engineering of CAR T cells to stably express the homeostatic chemokine receptor CCR7. In vitro killing assays hinted to a higher cytolytic capacity that could be tied to an altered cytoskeletal rearrangement. Human CAR and CAR.CCR7 T cells were generated by retroviral transduction and enriched by FACS at the end of the expansion phase (day 10), either without or with a previous over-night co-culture with target Jeko1 tumor cells that express the CAR target antigen CXCR5. Enriched cells were immediately processed for bulk mRNA Seq
2023-06-30 | E-MTAB-12778 | biostudies-arrayexpress
Project description:We aim to determine the difference of protein expression in the closely related Drosophila species D.melanogaster and D.simulans to gain further insight into protein expression profiles of both species. Analysis of the protein levels might hint to pathways that have evolved into different direction and explain the separation of th species from their common ancestors. Further, we try to characterize novel gene isoform by combining RNA sequencing and proteomics.
2019-02-25 | PXD005060 | Pride
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