Mechanisms of AICAR in lung cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE198777 | GEO | 2023/02/21
REPOSITORIES: GEO
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Project description:AICAR monophosphate (5-Aminoimidazole-4-carboxamide ribonucleotide) is a metabolic intermediate of the de novo purine synthesis pathway presenting highly promising metabolic and antiproliferative properties. Yeast mutants accumulating AICAR are auxotroph for histidine. A screening for suppressors of this phenotype identified recessive and dominant mutants that result in lowering intracellular AICAR concentration. The recessive mutants affect adenosine kinase which is shown here to catalyze the phosphorylation of AICAR riboside in yeast. The dominant mutants strongly enhance the capacity of the alkaline phosphatase Pho13p to dephosphorylate succinyl-AICAR monophosphate into the non-toxic riboside form. By combining these mutants to transcriptomic and metabolomic analyses, we establish that in yeast both toxic and physiological responses to AICAR are linked to the concentration of the monophosphate form, while the nucleoside moiety has no effect even at high concentration. Finally, we establish that (S)AICAR concentration varies under physiological conditions, thus modulating transcriptional regulation of purine pathway genes. This SuperSeries is composed of the SubSeries listed below.
2011-07-11 | GSE29324 | GEO
Project description:To identify genes transcriptionally regulated by AICAR under cellular stress, We treated NALM6 cells for 45 min with vehicle (DMSO) or AICAR (15 mM), and examined their RNA profile using RNA-Seq. The immediate early genes (IEGs) were identified as a subset of genes downregulated by AICAR.
2021-07-22 | GSE152917 | GEO
Project description:It has been demonstrated that CHIR99021 promotes self-renewal of mouse embryonic stem cells, however, the target genes of CHIR99021 is not fully understood. AICAR is the activator of AMP-activated protein kinase. It is reported that AICAR plays important role in mouse embryonic stem cells, however the moleculor mechanism of this phenomenon is unknown. To better understand the downstream target genes of CHIR99021 and AICAR, we performed Microarray analyses to identify their downstream targets. The data show the genes regulated by CHIR99021 or AICAR.
2013-01-01 | GSE40959 | GEO
Project description:U937 cells were treated wth 0.2 mM AICAr for 24 h to compare the results on cell line know to differentiate in the presence of AICAr with the results on primary patient sample.
2020-11-15 | E-MTAB-9537 | biostudies-arrayexpress
Project description:It has been demonstrated that CHIR99021 promotes self-renewal of mouse embryonic stem cells, however, the target genes of CHIR99021 is not fully understood. AICAR is the activator of AMP-activated protein kinase. It is reported that AICAR plays important role in mouse embryonic stem cells, however the moleculor mechanism of this phenomenon is unknown. To better understand the downstream target genes of CHIR99021 and AICAR, we performed Microarray analyses to identify their downstream targets. The data show the genes regulated by CHIR99021 or AICAR. J1 mESCs maintained in medium containing 1000 U/mL LIF and supplemented without or with CHIR99021 or AICAR for 24 hours, then total RNA was extracted for analysis.
2013-01-01 | E-GEOD-40959 | biostudies-arrayexpress
Project description:Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to functional cardiac decline and ultimately, congestive heart failure (HF). Impaired mitochondrial function and energetics are thought to be key factors driving progression into HF. We have previously shown in a rat model of chronic intravenous DOX-administration that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and oxidative metabolism, including fatty acid oxidation. We hypothesized that AMPK activation could restore mitochondrial number and function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this clinically relevant rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. This was associated with normalisation of substrate supply to the heart, as AICAR prevented DOX-induced dyslipidaemia. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number. In addition, we found that AICAR reduced the degree of myocardial atrophy, and RNAseq analysis showed that this was driven by normalisation of protein synthesis pathways, which are impaired in DOX-treated rat hearts. Taken together, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass.
2024-11-01 | GSE218397 | GEO
Project description:We have demonstrated AICAR can maintain J1 mouse ES cells pluripotency in our previous research, yet its effects on ES cells miRNAs expression remain a mystery. In this study, we performed small RNA (sRNA) High-throughput sequencing using Illumina HiSeq 2000 to investigate the influence of AICAR on J1 mouse ES cells miRNAs expression and further found the mechanism of how miRNAs affect ES cells pluripotency maintenance. Samples that treated by DMSO is used as a control. Compare microRNA expression of J1 mESC cultured with or without small molecule AICAR
2014-02-06 | E-GEOD-54586 | biostudies-arrayexpress
Project description:We investigated the role of Ado1p associated with AICAr supplementation on the global transcriptome of Y3188. The Y3188 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.
2011-08-31 | E-GEOD-29020 | biostudies-arrayexpress
Project description:We investigated the effects of AICAR and SAICAR accumulation on transcriptional regulation of purine biosynthesis and other metabolic pathways. These data were compared to those obtained in the ade16ade17 vs WT data set to determine the transcriptional effects associated to AICAR/SAICAR accumulation and those due to ade16 and ade17 deletions. In this work, global transcription analyses were combined to measurements of intracellular nucleotides pools by HPLC Keywords: Comparative genomic transcription analysis on total RNA from cells accumulating or lacking AICAR and SAICAR nucleotide derivatives.
2009-05-15 | GSE13183 | GEO
Project description:We investigated the effects of AICAr supplementation on the global transcriptome of Y2950. The Y2950 strain was grown with or without AICAr. For each comparison, we made 2 biological replicates, swapping dyes.
2011-08-31 | E-GEOD-29019 | biostudies-arrayexpress