Comparing effects of rapamycin and caffeine on gene expression in YPD media
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE4584 | GEO | 2006/04/04
SECONDARY ACCESSION(S): PRJNA94431
REPOSITORIES: GEO
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Project description:Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 signaling pathway inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprogramming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Although rapamycin showed a much more subtle effect on global translation than did caffeine, rapamycin was more effective in prolonging chronological lifespan. Rapamycin prolonged the lifespan of non-growing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.
2013-05-05 | E-MTAB-1489 | biostudies-arrayexpress
Project description:To comparatively analyze the transcriptional responses of yeast cells to the presence of rapamycin or caffeine the homozygous hoΔ/hoΔ strain of S. cerevisiae BY4743 were grown in fully controlled fermenters in the presence of 200 nM rapamycin or 5 mM caffeine. Cells were cultured overnight in YPD medium (2% [w/v] D-glucose, 2% [w/v] peptone, 1% [w/v] yeast extract) at 30°C in an orbital shaker at 180 rpm prior to the fermentations. For the cultivations in the fermenters defined synthetic medium was used. The batch cultivations were carried out in duplicates in 2L B-Braun Biostat B Plus fermenters with 1.5L working volume kept at 30°C with the rate of agitation at 800rpm. pH was controlled at 5.5 with 0.5M NaOH and HCl. Sampling was carried out at the mid-exponential phase of growth at an OD range of 0.6-0.8. Samples harvested for the transcriptome analysis were immediately frozen in liquid nitrogen and were stored at -80oC until RNA isolation.
2019-03-15 | E-MTAB-7373 | biostudies-arrayexpress
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: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: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: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
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.
2015-12-19 | GSE43030 | GEO
Project description:A caffeine-resistant Saccharomyces cerevisiae mutant strain was obtained using an evolutionary engineering strategy based on successive batch cultivation at gradually increasing caffeine levels. The mutant strain Caf905-2 was selected at a caffeine concentration where its reference strain could not grow at all. Whole-genome transcriptomic analysis of Caf905-2 was performed with respect to its reference strain.
2018-12-28 | GSE124452 | GEO
Project description:Purpose: This study aimed to identify differentially expressed genes including alternative splice variants in embryonic ventricles following in utero caffeine treatment. Methods: Pregnant CD-1 mice were injected with 20 mg/kg of caffeine or vehicle control daily from embryonic day (E) 6.5-9.5. On E10.5, total RNA was isolated from embryonic ventricles and used for transcriptomic RNA sequencing with Illumina HiSeq 2000 (1X75bp). RNA-seq reads were aligned to the mouse genome (build mm10) with the Tophat for Illumina tool in the PSU galaxy platform. Counting and annotation of RNA-seq reads as well as alternative splicing analysis were performed with Partek Genomics Suite version 6.11. Differential expression of gene and transcript reads between treatments was analyzed with R package EdgeR. Genes/transcripts with false discovery rate (FDR) less than 0.05 and absolute fold change greater than 1.5 were considered as significant. Differentially expressed genes were defined as genes with altered expression at either gene or transcript level. Unique differentially expressed genes were identified by combining the results from annotations with the RefSeq Transcripts (2013-05-10) or Ensembl Transcripts release 71 databases. Results: Differential expression analysis revealed that 59 genes and 451 transcripts were significantly up-regulated, and 65 genes and 398 transcripts were down-regulated by prenatal caffeine treatment (fold change >1.5 or <-1.5; p-value with FDR<0.05). In total, 900 unique genes were identified to have altered expression either at the gene or transcription level. Further analysis with Partek GS revealed that 183 genes had abnormal alternative splicing at the exon level after in utero caffeine treatment. Conclusions: In utero caffeine exposure caused gene expression changes in embryonic ventricles and these changes may lead to long-term effects on cardiac morphology and function. mRNA profiles in E10.5 heart ventricles treated with caffeine were generated by deep sequencing (n=2 for vehicle, n=3 for caffeine), using Illumina HiSeq 2000.
2015-01-07 | E-GEOD-56902 | biostudies-arrayexpress
Project description:Caffeine and trigonelline are the major bioactive compounds in coffee. Caffeine alone or combined with other coffee compounds shows hepatoprotective effects. However, molecular mechanisms underlying such hepatoprotective effects remain unclear. We therefore addressed molecular effects of caffeine and trigonelline on human hepatocytes using quantitative proteomics followed by bioinformatic analyses to obtain topological and functional significance. HepG2 cells were treated with 100 μM caffeine or trigonelline for 24-h and evaluated by quantitative proteomics using nanoLC-ESI-LTQ-Orbitrap MS/MS. A total of 27 and 26 significantly altered proteins were identified in caffeine-treated and trigonelline-treated cells, respectively, compared with control cells. Topological analyses revealed that ribosomal and translation regulatory proteins predominantly served as the hub proteins associated with protein clusters. Functional analyses also revealed that these two bioactive compounds shared some molecular mechanisms via induction of translational processes. There were also other unique molecular functions and biological processes triggered or suppressed by either caffeine or trigonelline. These data highlight common and unique molecular mechanisms underlying the hepatoprotective effects of caffeine and trigonelline that may be useful for future clinical applications.
2023-12-05 | PXD037553 | Pride