scholarly journals Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival

2016 ◽  
Vol 8 (324) ◽  
pp. 324ra16-324ra16 ◽  
Author(s):  
Guangrui Yang ◽  
Lihong Chen ◽  
Gregory R. Grant ◽  
Georgios Paschos ◽  
Wen-Liang Song ◽  
...  
Keyword(s):  
Clock Gene ◽  
The Core ◽  
Core Clock Gene

scholarly journals Circadian Expression of TIMP3 Is Disrupted by UVB Irradiation and Recovered by Green Tea Extracts

2019 ◽  
Vol 20 (4) ◽  
pp. 862 ◽  
Author(s):  
Sunyoung Park ◽  
Eun-Soo Lee ◽  
Nok-Hyun Park ◽  
Kyeonghwan Hwang ◽  
Eun-Gyung Cho
Keyword(s):  
Clock Gene ◽  
Regulatory Gene ◽  
Human Keratinocytes ◽  
Ultraviolet B ◽  
Rhythmic Expression ◽  
The Core ◽  
Circadian Expression ◽  
Tnf Α ◽  
Factor Α ◽  
Core Clock Gene

The human skin is the outermost physical barrier and has its own circadian machinery that works either cooperatively with the central clock, or autonomously. Circadian rhythms have been observed in many functions related to epidermal homeostasis including hydration and inflammation, and this functional oscillation is disturbed by ultraviolet radiation (UVR), which is a strong environmental cue. Among the genes estimated to show circadian expression in the skin, metalloproteinase inhibitor 3 (TIMP3), has a rhythmic expression in synchronized human keratinocytes similar to that of the core clock gene PER1 and an epidermal circadian regulatory gene, aquaporin 3 (AQP3) but was antiphase to the core clock gene BMAL1. Tumor necrosis factor-α (TNF-α), the regulatory target of TIMP3 via a disintegrin and metalloproteinase domain 17 (ADAM17), was inversely regulated when TIMP3 expression was downregulated by ultraviolet B (UVB) treatment. When synthetic TIMP3 peptides were applied to the cells, the secretion of TNF-α did not increase following the UVB treatment. Similar to TIMP3 peptides, Camellia sinensis leaf-derived extracts showed a distinguishing efficacy in recovering TIMP3 expression, downregulated by UVB treatment. Together, our results suggest that TIMP3 reversely mediates UVR-induced inflammation by being highly expressed during the daytime; therefore, recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients could at least in part inhibit the UVR-induced cellular phenomena.

scholarly journals Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization

2020 ◽  
Vol 8 ◽  
Author(s):  
Lee Shaashua ◽  
Shimrit Mayer ◽  
Chen Lior ◽  
Hagar Lavon ◽  
Alexander Novoselsky ◽  
...  
Keyword(s):  
Clock Gene ◽  
Tumor Initiation ◽  
Metastatic Colonization ◽  
The Core ◽  
Period 2 ◽  
Core Clock Gene

scholarly journals The Adrenal Clock Prevents Aberrant Light-Induced Alterations in Circadian Glucocorticoid Rhythms

Endocrinology ◽  
2018 ◽  
Vol 159 (12) ◽  
pp. 3950-3964 ◽  
Author(s):  
William C Engeland ◽  
Logan Massman ◽  
Shubhendu Mishra ◽  
J Marina Yoder ◽  
Sining Leng ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Clock Gene ◽  
Cholesterol Metabolism ◽  
Ex Vivo ◽  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Targeted Deletion ◽  
The Core ◽  
Steroidogenic Acute Regulatory ◽  
Core Clock Gene

Abstract The glucocorticoid (GC) rhythm is entrained to light-dark (LD) cycles via a molecular clock in the suprachiasmatic nucleus (SCN) and is maintained by an adrenal clock synchronized by SCN-dependent signals. Targeted deletion of the core clock gene Bmal1 can disrupt adrenal clock function. The requirement of the adrenal clock to stabilize the circadian GC rhythm during exposure to aberrant LD cycles was determined using novel aldosterone synthase (AS)Cre/+::Bmal1Fl/Fl mice in which Bmal1 deletion occurred during postnatal adrenal transdifferentiation. To examine whether adrenal Bmal1 deletion results in loss of the adrenal clock, mice were crossed with mPER2::Luciferase (mPER2Luc/+) mice. Adrenals from ASCre/+::Bmal1+/+::PER2Luc/+ [control (CTRL)] mice show mPER2Luc rhythms ex vivo, whereas slices from ASCre/+::Bmal1Fl/Fl::PER2Luc/+ [knockout (KO)] mice show dampened rhythms. To monitor corticosterone rhythmicity, mice were implanted with subcutaneous microdialysis probes and sampled at 60-minute intervals for up to 3 days under 12:12-hour [τ (T) 24] LD or 3.5:3.5-hour (T7) LD cycles. Corticosterone rhythms were entrained to T24 LD in CTRL and KO mice. Under T7 LD, circadian corticosterone rhythms persisted in most CTRL mice but not KO mice. Hyperadrenocorticism also was observed in KO mice under T7 LD, reflected by increased corticosterone peak amplitude, total daily corticosterone, and responses to ACTH. Analysis of dysregulated adrenal genes in KO mice exposed to aberrant light identified candidates involved in cholesterol metabolism and trafficking, including steroidogenic acute regulatory protein, which could increase steroidogenesis. Our results show that the adrenal clock functions to buffer steroidogenic responses to aberrant light and stabilize circadian GC rhythmicity.

scholarly journals Cell-intrinsic, Bmal1-dependent Circadian Regulation of Temozolomide Sensitivity in Glioblastoma

2017 ◽  
Vol 32 (2) ◽  
pp. 121-129 ◽  
Author(s):  
Emily A. Slat ◽  
Jasmin Sponagel ◽  
Luciano Marpegan ◽  
Tatiana Simon ◽  
Najla Kfoury ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Growth Inhibition ◽  
Clock Gene ◽  
Daily Rhythms ◽  
The Core ◽  
Circadian Time ◽  
Damage Response ◽  
Human And Mouse ◽  
Core Clock Gene

The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1. Deletion of Bmal1 (Arntl) abolished circadian rhythms in gene expression and TMZ-induced activation of apoptosis and growth inhibition. These data indicate that tumor cell-intrinsic circadian rhythms are common to GBM tumors and can regulate TMZ cytotoxicity. Optimization of GBM treatment by timing TMZ administration to daily rhythms should be evaluated in prospective clinical trials.

scholarly journals Shifting the Circadian Rhythm of Feeding in Mice Induces Gastrointestinal, Metabolic and Immune Alterations Which Are Influenced by Ghrelin and the Core Clock Gene Bmal1

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e110176 ◽  
Author(s):  
Jorien Laermans ◽  
Charlotte Broers ◽  
Kelly Beckers ◽  
Laurien Vancleef ◽  
Sandra Steensels ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Clock Gene ◽  
The Core ◽  
Immune Alterations ◽  
Core Clock Gene

scholarly journals Night-time feeding of Bmal1−/− mice restores SCFA rhythms and their effect on ghrelin

2020 ◽  
Vol 245 (1) ◽  
pp. 155-164 ◽  
Author(s):  
Anneleen Segers ◽  
Louis Desmet ◽  
Shu Sun ◽  
Kristin Verbeke ◽  
Jan Tack ◽  
...  
Keyword(s):  
Clock Gene ◽  
Clock Genes ◽  
Short Chain Fatty Acids ◽  
Inhibitory Effect ◽  
Diurnal Rhythms ◽  
Feeding Time ◽  
Night Time ◽  
The Core ◽  
Core Clock Gene

The known crosstalk between short-chain fatty acids (SCFAs) and the circadian clock is tightly intertwined with feeding time. We aimed to investigate the role of the core clock gene Bmal1 and feeding time in the diurnal rhythms in plasma and caecal SCFA levels and in their effect on the release of the hunger hormone ghrelin in the stomach and colon. WT, Bmal1-/- (ad libitum fed) and night-time-restricted-fed (RF)-Bmal1-/- littermates were killed at zeitgeber time (ZT) 4 and 16. SCFA concentrations were measured by gas chromatography. To investigate the effect of SCFAs on ghrelin release, stomach and colonic full-thickness strips were incubated with Krebs or a SCFA mix mimicking plasma or caecal concentrations, after which octanoyl ghrelin release was measured by RIA. Diurnal rhythms in caecal and plasma SCFAs oscillated in phase but rhythmic changes were abolished in Bmal1-/- mice. RF of Bmal1-/- mice restored fluctuations in caecal SCFAs. Plasma SCFA concentrations failed to affect gastric ghrelin release. The effect of caecal SCFA concentrations on colonic ghrelin release was rhythmic (inhibition at ZT 4, no effect at ZT 16). In Bmal1-/- mice, the inhibitory effect of SCFAs at ZT 4 was abolished. RF Bmal1-/- mice restored the inhibitory effect and increased colonic Clock expression. To conclude, diurnal fluctuations in caecal SCFAs and the effect of SCFAs on colonic ghrelin release are regulated by feeding time, independent of the core clock gene Bmal1. However, local entrainment of other clock genes might contribute to the observed effects.

scholarly journals PI3K-PTEN dysregulation leads to mTOR-driven upregulation of the core clock gene BMAL1 in normal and malignant epithelial cells

Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 42393-42407 ◽  
Author(s):  
Camila S. Matsumoto ◽  
Luciana O. Almeida ◽  
Douglas M. Guimarães ◽  
Manoela D. Martins ◽  
Petros Papagerakis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Clock Gene ◽  
The Core ◽  
Core Clock Gene

scholarly journals The core clock gene, Bmal1, and its downstream target, the SNARE regulatory protein secretagogin, are necessary for circadian secretion of glucagon-like peptide-1

2020 ◽  
Vol 31 ◽  
pp. 124-137 ◽  
Author(s):  
Andrew D. Biancolin ◽  
Alexandre Martchenko ◽  
Emilia Mitova ◽  
Patrick Gurges ◽  
Everan Michalchyshyn ◽  
...  
Keyword(s):  
Clock Gene ◽  
Regulatory Protein ◽  
Downstream Target ◽  
The Core ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Core Clock Gene
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