Project description:AICAR is a metabolite with anti-tumoral properties. Its monophosphate derivative ZMP is an AMP mimetic activator of the protein kinases AMPK. However, AICAR also mediates AMPK-independent effects. A kinetic transcriptome analysis was therefore carried out in Ampkα1/α2 double knockout murine embryonic fibroblasts in response to AICAR in order to unveil these AMPK-independent functions,
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.
Project description:Transcriptional profiling of human prostate cancer cell line LNCaP treated with Metformin or AICAR compared to control non-stimulated LNCaP.
Project description:The purpose of the research is to delineate the mechanism behind AICAR-induced cytotoxicity by understanding the genetic pathways that are affected with AICAR treatment.
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.
Project description:We used microarrays to detail the action of AICAR on the transcriptome response to CD40-ligation and IL-4 stimulation in Daudi cells. Keywords: gene expression array-based, response to anti-CD40 and/or IL-4 with or without AICAR
Project description:Previous stimulation experiments of stimulated primary murine colonic fibroblasts with IL-36R ligands for 4h in vitro showed an upregulation of pro-inflammatory cytokines e.g. IL-6, IL-1b and chemokines e.g. CXCL1, CCL2 indicating an important role for IL-36 in inflammation. We were interested in analyzing long-term stimulation (9 days) of intestinal fibroblasts to identify a putative differential expression profile. The experimental setup included 6 samples from 3 colons in a pairwise design (3 stimulated vs 3 unstimulated).
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.