Effect of caffeine on WT versus 3HA-TOR1 [I1954V + W2176R]
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE4586 | GEO | 2006/04/04
SECONDARY ACCESSION(S): PRJNA94435
REPOSITORIES: GEO
Similar Datasets
Project description:Effect of caffeine on WT versus 3HA-TOR1 [I1954V + W2176R]
| PRJNA94435 | ENA
Project description:Caffeine is a natural purine analog that elicits pleiotropic effects, which ultimately lead to cell death by a mechanism that is still largely uncharacterized. This drug can activate the PKC1-MAPK cell integrity pathway, as shown by phosphorylation of Mpk1 kinase. However, and contrary to expectation, the caffeine-induced hyperphosphorylation of Mpk1 was accompanied by a negligible activation of its downstream targets Rlm1 and SBF transcription factors, which suggested that the fortification of the cell wall induced by caffeine was independent on the MAP kinase activation. This result was consistent with the finding that the loss of RLM1 had no consequence on the increased resistance of caffeine-treated cells to zymolyase, and was further consolidated by a genome-wide microarray analysis showing that, contrary to the cell wall drugs Congo Red and Calcofluor white, caffeine did not cause upregulation of Rlm1-dependent genes encoding cell wall remodeling enzymes. Interestingly, this global expression analysis revealed a striking resemblance of the transcriptomic responses to caffeine with those of rapamycin, a potent inhibitor of the TOR1 and TOR2 kinases. Consistent with this analysis, we found that the caffeine-induced phosphorylation of Mpk1 was lost in a tor1(delta) mutant but it was conserved in a TOR1-1 strain bearing a rapamycin-insensitive Tor1 kinase. Also, and contrary to the mechanism by which rapamycin led to activation of the PKC pathway, the caffeine-dependent process did not necessitate cell wall sensors and was completely abolished upon deletion of ROM2 encoding a GDP/GTP exchange factor of the Rho1-PKC pathway. Moreover, addition of caffeine to yeast cells resulted in a transient drop in intracellular cAMP, and this effect was not observed in a rom2(delta) mutant. In summary, our results revealed that Tor1 is a potential direct target of caffeine in yeast, whose inhibition leads to activation of the Pkc1-Mpk1 kinase cascade and inhibition of the Ras/cAMP pathway, and that for this specific case, the cross-talk between these signaling pathways is mediated by Rom2. These results may have broad implication for our understanding of caffeine effects in analogous regulatory networks in mammalian cells. Key words: caffeine, antifungal drugs, cell wall, transcript profiling, TOR, PKC1, RAS/cAMP. Keywords: time course, dose response
2006-11-03 | GSE4049 | 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:To identify genes influenced by rapamycin and caffeine in strains W303a, S288c, and Sigma 2000 Keywords: Drug dose response
2006-04-04 | GSE4584 | 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. 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: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: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: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