Caffeine-regulated transcripts in mouse hearts are p27-dependent
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE100489 | GEO | 2017/11/30
SECONDARY ACCESSION(S): PRJNA391941
REPOSITORIES: GEO
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Project description:Interventions: Drinking three cups of coffee with 100 mg caffeine in hot water 100 mL in one day, beginning on the morning after surgery at 7.00, 12.00, 17.00 within 30 minutes under the supervision (a nurse or a doctor).,Drinking three cups of coffee with 50 mg caffeine in hot water 100 mL in one day, beginning on the morning after surgery at 7.00, 12.00, 17.00 within 30 minutes under the supervision (a nurse or a doctor).;Active Comparator Other,Active Comparator Other;100 mg caffeine,50 mg caffeine
Primary outcome(s): the time to first flatus after drink coffee based on the patient own statements
Study Design: Randomized
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Project description:Caffeine is a well-known purine alkaloid commonly found in coffee. Several lines of previous and recent evidence have shown that habitual coffee drinking is associated with lower risks for chronic kidney disease (CKD) and nephrolithiasis. However, cellular and molecular mechanisms underlying its renoprotective effects remain largely unknown due to a lack of knowledge on cellular adaptive response to caffeine. This study investigated cellular adaptive response of renal tubular cells to caffeine at the protein level. Cellular proteome of MDCK cells treated with caffeine at a physiologic concentration (100 μM) for 24 h was analyzed comparing with that of untreated cells by label-free quantitative proteomics. From a total of 936 proteins identified, comparative analysis revealed significant changes in levels of 148 proteins induced by caffeine. These significantly altered proteins were involved mainly in proteasome, ribosome, tricarboxylic acid (TCA) (or Krebs) cycle, DNA replication, spliceosome, biosynthesis of amino acid, carbon metabolism, nucleocytoplasmic transport, cell cycle, cytoplasmic translation, translation initiation, and mRNA metabolic process. Functional validation by various assays confirmed that caffeine decreased cell population at G2/M, increased cell population at G0/G1, increased level of ubiquitinated proteins, increased intracellular ATP and enhanced mitochondrial membrane potential in MDCK cells. These data may help unravelling molecular mechanisms underlying the biological effects of caffeine on renal tubular cells at cellular and protein levels.
2023-12-11 | PXD045313 | Pride
Project description:Our previous research demonstrated that caffeine exposure on embryonic day (E) 8.5 increased body weight, altered cardiac morphology and function in adult male mice. However, these adverse effects were not observed in adenosine A1 receptor knockout (A1AR-/-) mice. Our hypothesis is that A1AR action mediates changes in DNA methylation patterns in mice exposed in utero to caffeine and that these changes in methylation lead to long-term effects in adult mice. To test this hypothesis, DNA Methylation 2.1M Deluxe Promoter Arrays (NimbleGen) were used to examine the methylation patterns of DNA isolated from adult left ventricles of the A1AR knockout line exposed to 20 mg/kg caffeine at E8.5 in utero. In A1AR+/+ mice, 4,896 hypermethylated and 2,823 hypomethylated regions were discovered in the left ventricles of the caffeine group compared to the normal saline group. In A1AR-/- mice, 1,024 hypermethylated and 1,757 hypomethylated regions were found in the caffeine group. The differentially methylated regions (DMRs) in the caffeine treated A1AR+/+ hearts mapped to 6,148 genes, 4,853 promoters, 4,111 primary transcripts, 816 CpG islands, and 98 miRNAs. Functional annotation clustering of genes revealed that many genes were involved in the development of hypertrophic cardiomyopathy and other heart diseases, which may explain our earlier findings of thickening of the left ventricular wall after in utero caffeine treatment. The methylation changes in several DMRs, mef2c, ins2, tnnt2, and myh6, were validated by bisulfite sequencing. In summary, in utero caffeine exposure caused DNA methylation changes in adult left ventricles and that these changes may be mediated by A1ARs. Pregnant mice were injected at embryonic day 8.5 with 0.9% NaCl (vehicle) or 20 mg/kg caffeine in vehicle i.p. Pups were born and raised until 8-10 weeks of age. Analysis was performed on the following groups vehicle A1AR+/+ (veh+/+), vehicle A1AR-/- (veh-/-), caffeine A1AR+/+ (caff+/+), and caffeine A1AR-/- (caff-/-). Genomic DNA from left ventricles of adult male mice was used. Two biological replicates were measured for each group.
2015-12-19 | E-GEOD-43030 | biostudies-arrayexpress
Project description:This project aims to identify p27 modification sites.
2023-01-05 | PXD039223 | Pride
Project description:Genetic variants in gene regulatory sequences can modify gene expression and mediate the molecular response to environmental stimuli. In addition, genotype–environment interactions (GxE) contribute to complex traits such as cardiovascular disease. Caffeine is the most widely consumed stimulant and is known to produce a vascular response. To investigate GxE for caffeine, we treated vascular endothelial cells with caffeine and used a massively parallel reporter assay to measure allelic effects on gene regulation for over 43,000 genetic variants. We identified 665 variants with allelic effects on gene regulation and 6 variants that regulate the gene expression response to caffeine (GxE, false discovery rate [FDR] < 5%). When overlapping our GxE results with expression quantitative trait loci colocalized with coronary artery disease and hypertension, we dissected their regulatory mechanisms and showed a modulatory role for caffeine. Our results demonstrate that massively parallel reporter assay is a powerful approach to identify and molecularly characterize GxE in the specific context of caffeine consumption.
2024-02-26 | GSE221514 | GEO
Project description:Rhodococcus sp. P27 Genome sequencing and assembly
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Project description:Cisplatin (CP) is a chemotherapeutic drug that is used to cure different types of cancer. CP induces DNA damage and leads to cell cycle arrest. The cyclin-dependent kinase inhibitor 1B (CDKN1B), also termed p27, plays an important role in the drug response ; and increased levels of p27 correlated with CP resistance. In HEK293 cells, we observed that p27 mRNAs levels increased whereas protein level drastically decreased in cells treated with CP; suggesting post-transcriptional regulatory events. To further understand the underlying mechanisms, we applied a biochemical approach combined with mass-spectrometry to systematically identify the RNA-binding proteins (RBPs) that are bound to the 3’UTR of p27 mRNAs in CP-treated versus non-treated cells in vivo. We found that 24 proteins, most of them known RBPs such HuR, hNRNPD, changed their association with p27 mRNA upon CP treatement. Furthermore, knock-down of a subset of the identified RBPs led to the inhibition of the CP-induced increase of p27 mRNA levels. In conclusion, these results highlight substantial rearrangement between RBPs and p27 mRNA upon CP treatment and corroborate the importance of post-transcriptional control in cellular drug response.
2019-09-27 | PXD008498 | Pride
Project description:To screen for xenobiotic-metabolizing-enzyme genes (XME) induced by caffeine exposure, a microarray experiment (performed with a Drosophila pangenomic array (Agilent 4 X 44K) was carried out between control and individuals exposed to caffeine (18mM ). Among 23401 genes consistantly found in the three biological replicates, 13108 showed a significant variation. 749 genes were over-expressed whereas 1518 were under-expressed. Interestingly, several genes belonging to all major classes of detoxification enzymes including XME were among the most highly induced such as CYP12d1, CYP6a8 and CYP6d5. Caffeine ingestion induced gene expression in Drosophila melanogaster male thorax and abdomen was mesured at 12h after exposure to doses of 0, 18mM of caffeine. Three independant experiments were performed at each dose using different drosophila for each experiment.
2014-07-04 | E-GEOD-59084 | biostudies-arrayexpress
Project description:We report the genome-wide profile of cJun and p27 in _231 (a line selected for low metastatic ability), _231-1833 (its bone-tropic metastatic derivative line), _231p27CK-DD (a phosphomimetic cell line), and _231-1833shp27 (p27 knockdown cell line). It shows that cJun and p27 broadly binds to genomic DNA and their bindings are regulated by p27 phosphorylation-dependent patterns.
2019-03-19 | GSE112444 | GEO
Project description:Proteasomes hydrolyze most intracellular proteins. Immunoproteasome is a specific form of proteasome implicated in inflammation, cancer and autoimmune diseases. Modulation of immunoproteasome activity and content is a promising direction for the management of socially important pathologies. Using previously obtained reporter colorectal cancer cell lines, we tested how various commonly used compounds including ibuprofen, acetylsalicylic acid, vitamin C, caffeine and others, affect immunoproteasome expression. Methods: Immunoproteasome subunit expression was assessed by flow cytometry, qPCR and Western blot. Proteasome activity was tested using fluorogenic substrates and the activity probe. Transcriptome analysis was performed to identify patterns of gene expression changes. Results: Among the tested compounds caffeine was the only drug that revealed modest reduction in quantity of immunoproteasomes. The effect of caffeine on immunoproteasomes varied between cell lines and was stronger as a result of prolonged treatment. The reduction of immunoproteasome content in cells treated with caffeine coincided with decreased expression of immunoproteasome subunits and downregulation of Nrf3 transcription factor and a PAC4 proteasome assembly chaperone. Moreover, decreased expression of immunoproteasome subunits in cells treated with caffeine coincided with the reduction of oxidative stress levels. Caffeine did not affect the degradation of immunoproteasomes by autophagy. Conclusions: Modulation of immunoproteasome expression by caffeine might help to optimize existing and develop novel strategies for the treatment of colorectal cancer and several autoimmune diseases.
2024-10-22 | GSE279800 | GEO