Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

58 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

ABSTRACT: Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenine and guanine nucleotides. We describe a new early-onset distinct neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new potentially treatable early-onset neurodegenerative disease. An 18 chip study, that compares iPSC derived neural progenitor cells from two individuals: a patient with pontocerebellar hypoplasia and an unaffected parent. Samples are run as either non-treated, treated with Adenosine, or treated with Adenosine and AICAr. Three replicates are included for every individuals in every treatment condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Eric Scott

PROVIDER: E-GEOD-46615 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

AMPD2 Regulates GTP Synthesis and is Mutated in a Potentially-Treatable Neurodegenerative Brainstem Disorder

Project description:Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenine and guanine nucleotides. We describe a new early-onset distinct neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new potentially treatable early-onset neurodegenerative disease.

2013-12-01 | GSE46615 | GEO

EHUA Vibrio alginolyticus EPGS Nimblegen

Project description:Vibrio alginolyticus is a Gram-negative marine bacterium. A limited population of the organisms causes acute gastroenteritis in humans. In this study, Vibrio alginolyticus wild type strain EPGS is compared with the mutants of Ser-Thr kinase PpkA and phosphatase PppA, after cultured for 7h, in Luria-Bertani containing medium 3 % NaCl at 30 C. Our goal is to determine the ppkA and pppA regulon. Three wild type and five mutant Vibrio alginolyticus samples were compared.

2011-12-31 | E-GEOD-24319 | biostudies-arrayexpress

Identification of the Saccharomyces cerevisiae ZMP binders

Project description:5′-phosphoribosyl-5-amino-4-imidazole carboxamide monophosphate (ZMP) is a metabolic intermediate of the de novo purine biosynthesis pathway. Its accumulation in several cell types from bacteria to human is associated with growth impairment. Identification of ZMP-binding proteins was performed to understand the molecular basis of ZMP toxicity. To assess the specificity of ZMP-binding proteins, an affinity chromatography approach was also applied to the closely related molecules AMP, SZMP (Succinyl-ZMP) and AICAR (5-amino-4-imidazole carboxamide ribonucleoside, also named Acadesine).

2018-11-21 | PXD007780 | Pride

Proteomics based analysis for associated PD-L1 in macrophage stimulated with extracellular adenosine signaling

Project description:We performed proteomics analysis to discover effector proteins for the post-transcriptional regulation of PD-L1 onhuman macrophages stimulated by adenosine signal.

2022-10-14 | PXD024512 | Pride

Rat MeDIP Array, naïve, epileptic, and adenosine treated

Project description:Epilepsy causes altered gene expression; transient adenosine treatment inhibits progression of epileptogenesis Hippocampus of epileptic rat is hypermethylated compared to naïve; adenosine treatment causes hypomethylation Metylation state in epileptic rats (9 weeks post kainic acid induced status epilepticus) was compared to naïve (untreated) rats and epileptic rats treated with adenosine for 5 days

2013-09-05 | E-GEOD-45932 | biostudies-arrayexpress

Genome-wide transcriptional responses to nucleotides in zebrafish (Danio rerio) embryos

Project description:Purpose:To investigate the transcriptomic profiles in zebrafish embryos exposed externally to nucleotides at a critical develpomental window (3-7 days post fertilization) determine biological processes and pathways based on differentially expressed gene transcripts using High Throughput Sequencing (HTS). Methods:Total mRNA profiles of 7 dpf zebraifsh embryos after exposure to 10-5M ATP, AMP, adenosine and adenine were generated by deep sequencing, in triplicate, using Illumina HiSeq2500 Results: There were many differentially expressed genes; including ubiquitin-, actin-, and tubulin-related, showing that the cytoskeleton was altered; other DEGs involved with purine binding, specifically guanine, which was expected as the mixture was composed of purines; DEGs involved with GTP binding were also upregulated, suggesting increased cell signaling,

2020-03-23 | GSE97016 | GEO

Expression data from RAW 264.7 macrophage

Project description:IFNg is a pro-inflammatory and pro-atherogenic cytokine that leads to macrophage activation. Adenosine has well-documented anti-inflammatory properties. We used microarrays to compare the global gene expression profile in mouse macrophages stimulated with IFNg alone and those cells treated with IFNg and adenosine. We determined that adenosine suppressed the expression of many IFNg-regulated pro-inflammatory cytokines, chemokines, and other pro-atherogenic genes. Keywords: treatment response RAW 264.7 cells were treated for 4 hours with either IFNg or IFNg plus adenosine. Following treatment, total RNA was extracted and treatment groups were pooled from 2 separate experiments for hybridization of Affymetrix microarrays.

2009-12-30 | E-GEOD-14612 | biostudies-arrayexpress

Transcriptome of primary acute myeloid leukemia (AML) cells treated with AICAr

Project description:Ribonucleoside AICAr, a precursor in purine synthesis and a known activator of AMPK, was shown to induce monocytic differentiation in AML cell lines by inducing pyrimidine depletion followed by activation of ATR/Chk1 pathway and cell cycle arrest. Here we report transcriptional changes induced by AICAr in the primary AML sample (FAB-M2, FLT3 negative, NPM1 negative) in which AICAr induced differentiation and accumulation of macrophage cells in vitro. RNA-seq transcriptome analysis of primary AML cells isolated from the bone marrow of a patient with de novo FAB-M2 AML. Mononuclear cells were isolated from the bone marrow sample by density gradient separation and grown in RPMI supplemented with 10% FBS, 2 mM L-glutamine, 50 U/ml penicillin, 50 μg/ml streptomycin and 50 ng/ml IL-3, IL-6, SCF and FLT3L. Cells were treated with AICAr (0.4 mM) for 24 h. Experiment was performed in biological triplicates and total RNA was isolated for transcriptome analysis using Illumina high throughput sequencing.

2020-11-01 | E-MTAB-9209 | biostudies-arrayexpress

Effect of OVO-like 1 knockdown on global transcript expression in differentiated BeWo trophoblast cells

Project description:We had previously discovered that the transcription factor OVO-like 1 (OVOL1) was highly induced during trophoblast differentiation. In this study, we used an lentiviral shRNA strategy to decrease OVOL1 expression in BeWo trophoblast cells. Control cells were transduced with shRNAs targeting no known mammalian transcript (shCont). Following stimulation of differentiation (48h exposure to 8-bromo-cyclic adenosine monophosphate), a RNA-seq approach was used to determine global transcript differences in OVOL1-knockdown cells compared to control cells. Trophoblast cells transduced with control shRNAs were used as controls. Cells transduced with shRNAs targeting OVOL1 were used as treatment. All cells received 250 uM 8-bromo-cyclic adenosine monophosphate to stimulate differentiation. Three independent replicates of control and treatment groups were analyzed.

2015-08-01 | E-GEOD-66962 | biostudies-arrayexpress

A novel transcription factor PunR and Nac are involved in purine and purine nucleoside transporter punC regulation in E. coli

Project description:Recently, novel analytic methods have divided bacterial transcriptomes into independently modulated sets of genes (iModulons). Functionally annotated iModulons that contain y-genes lead to testable hypotheses to elucidate y-gene function. The inversely correlated expression of a putative transporter gene, ydhC, relative to purine biosynthetic genes, has led to the hypothesis that it encodes a purine-related transporter and revealed a LysR-family regulator, YdhB, with a predicted 23-bp palindromic binding motif. RNA-Seq analysis of a ydhB knockout mutant confirmed the YdhB-dependent activation of ydhC in the presence of adenosine. The deletion of either the ydhC or the ydhB gene led to a substantially decreased growth rate for E. coli in minimal medium with adenosine, inosine, or guanosine as the nitrogen source. Taken together, we provide clear evidence that YdhB activates the expression of the ydhC gene that encodes a novel purine transporter in E. coli. We propose that the genes ydhB and ydhC be re-named as punR and punC, respectively.

2021-04-28 | GSE173410 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data