Modulation of immunomodulatory peptide activity by 2-deoxy-d-glucose
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE74508 | GEO | 2016/10/29
SECONDARY ACCESSION(S): PRJNA300622
REPOSITORIES: GEO
Similar Datasets
Project description:Perinatal brain injury is a major clinical problem associated with high neonatal mortality and morbidity and an increased risk of life-long chronic disabilities. Despite improved survival rates, the absolute numbers of neurological handicaps of perinatal origin have not decreased. There is currently no pharmacological treatment providing neuroprotction in neonates. As activation of the innate immune response is a key contributing factor to brain injury in both term and preterm infants we investigated the therapeutic potential of novel immunomodulatory innate defence regulator peptides (IDRs) in perinatal brain injury. IDR-1018 significantly reduced the production of inflammatory mediators by LPS-stimulated microglia cells in vitro. IDR-1018 was also neuroprotective in a clinically-relevant animal model of neonatal brain injury, exerting effects on regulatory molecules of TLR-, Ca2+- and p53-signaling. Of utmost importance, IDR-1018 markedly protected both white and grey brain matter when administered after the injury, thus has tremendous applicability to the clinical setting. Here we demonstrate for the first time that peripheral administration of an immunomodulatory peptide is neuroprotective in vivo in a clinically relevant model of perinatal brain damage.
2016-09-17 | GSE36215 | GEO
Project description:Perinatal brain injury is a major clinical problem associated with high neonatal mortality and morbidity and an increased risk of life-long chronic disabilities. Despite improved survival rates, the absolute numbers of neurological handicaps of perinatal origin have not decreased. There is currently no pharmacological treatment providing neuroprotction in neonates. As activation of the innate immune response is a key contributing factor to brain injury in both term and preterm infants we investigated the therapeutic potential of novel immunomodulatory innate defence regulator peptides (IDRs) in perinatal brain injury. IDR-1018 significantly reduced the production of inflammatory mediators by LPS-stimulated microglia cells in vitro. IDR-1018 was also neuroprotective in a clinically-relevant animal model of neonatal brain injury, exerting effects on regulatory molecules of TLR-, Ca2+- and p53-signaling. Of utmost importance, IDR-1018 markedly protected both white and grey brain matter when administered after the injury, thus has tremendous applicability to the clinical setting. Here we demonstrate for the first time that peripheral administration of an immunomodulatory peptide is neuroprotective in vivo in a clinically relevant model of perinatal brain damage. In this second data set, adult mice were used for comparison.
2016-09-17 | GSE51026 | GEO
Project description:Background: C. elegans fed with a chemical inhibitor of glucose, namely 2-deoxy-D-glucose (DOG), exhibit considerably extended life span. DOG, in contradiction to D-glucose, cannot be metabolized in the glycolytic pathway. This results in the fact that less glucose is available for ATP production, and thus makes DOG-feeding of the roundworms equivalent to glucose restriction. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
2013-11-06 | GSE46344 | GEO
Project description:Background: C. elegans fed with a chemical inhibitor of glucose, namely 2-deoxy-D-glucose (DOG), exhibit considerably extended life span. DOG, in contradiction to D-glucose, cannot be metabolized in the glycolytic pathway. This results in the fact that less glucose is available for ATP production, and thus makes DOG-feeding of the roundworms equivalent to glucose restriction. The RNA-seq data comprises 4 age groups (1, 5, 10 and 20 days after L4) 11 samples: mRNA profiles of 1-day, 5-day and 10-day old worms as triplicates for DOG treatment; mRNA profiles of 20-day old worms as duplicates for DOG treatment
2013-11-06 | E-GEOD-46344 | biostudies-arrayexpress
Project description:Neuroprotection by a novel immunomodulatory peptide
| PRJNA219711 | ENA
Project description:Single-cell level measurements are necessary to characterize the intrinsic biological variability in a population of cells. In a study of the metabolic response of a clonal Saccharomyces cerevisiae population challenged by the glycolytic inhibitor 2-deoxy-D-glucose (2-DG), this variability is shown here, by comparing measurements at the population and the single-cell level. A novel microarray platform and MALDI mass spectrometric read-out allow us to follow 24 parameters simultaneously, in up to 100 single-cell measurements. Correlation plots for metabolites from the glycolytic pathway, the pentose phosphate pathway, and the observed ATP/ADP ratio as a measure of cellular energy charge give new insight into biochemical and metabolic pathways, which would not be accessible from population-level metabolomics data. Single-cell level measurements are necessary to characterize the intrinsic biological variability in a population of cells. In this study we demonstrate that with the Microarrays for Mass Spectrometry (MAMS) platform we are able to observe this variability. We monitor environmentally-(2-deoxy-D-glucose) and genetically-(∆PFK2) perturbed Saccharomyces cerevisiae cells both at the population and near single-cell levels. Correlation plots between metabolites from the glycolytic pathway, as well as with the observed ATP/ADP ratio as a measure of cellular energy charge give new biological insight that is not accessible from population-level metabolomic data.
2013-05-22 | MTBLS29 | MetaboLights
Project description:2-deoxy-D-glucose (2DG) is a glucose analog that is established to inhibit glucose metabolism via glycolysis. It has long been recognized as a potential chemical mimetic of calorie restriction, and it also has been shown to have anti-viral effects in infected cells, against among others SARS-CoV-2. This study aimed to determine whether intermittent treatment of mice with 2DG could alter nutrient metabolism in vivo and whether this would produce a proteomic signature of altered glucose metabolism and other cellular pathways, with a view to explaining the anti-viral properties of 2DG. Parallel physiological studies of the heart aimed to relate any proteomic changes to the function and performance of the heart, including assessing whether there were any signs of detrimental effects of 2DG.
2022-05-20 | PXD027974 | Pride
Project description:Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defenses peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on macrophages/monocytes. Here we measured the effect of IDR-1018 on macrophage gene expression during differentiation. Differentiation in the presence of IDR-1018 induced a unique signature of immune responses suggesting that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection.
2013-10-16 | GSE40131 | GEO
Project description:Heparan sulfate (HS), a long linear polysaccharide, is implicated in various steps of tumorigenesis, including angiogenesis. We successfully interfered with HS biosynthesis using a peracetylated 4-deoxy analog of the HS constituent GlcNAc and studied the compound’s metabolic fate and its effect on angiogenesis. The 4-deoxy analog was activated intracellularly into UDP-4-deoxy-GlcNAc and HS expression was inhibited up to ~96% (IC50 = 16 µM). HS chain size was reduced, without detectable incorporation of the 4-deoxy analog, likely due to reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity. Comprehensive gene expression analysis revealed reduced expression of genes regulated by HS binding growth factors as FGF-2 and VEGF. Cellular binding and signaling of these angiogenic factors was inhibited. Micro-injection in zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was inhibited in both zebrafish and chicken model systems. All these data identify 4-deoxy-GlcNAc as a potent inhibitor of HS synthesis which hampers pro-angiogenic signaling and neo-vessel formation.
2013-08-23 | GSE48284 | GEO
Project description:The RNA samples from HT-29 (ATCC) colon cancer cell line were reverse transcribed into cDNAs and categorized in 3 groups with different concentrations of 5-aza-deoxy-cytidine (5-Aza); in each group three replicative 150 mm cultures were treated with: 1) dimethyl sulfoxide (vehicle alone, 0 μM 5-Aza); 2) 5μM 5-Aza and 3) 10 μM 5-Aza; for five days We then used Affymetrix microarray platform to profile the gene expression of the 3 HT29 cell groups (3 replicates in each group) in order to search for differentially expressed genes The transcriptional response of HT-29 (ATCC) colon cancer cell line under 3 concentrations of 5-aza-deoxy-cytidine was investigated based on their RNA expression profiles
2013-09-17 | E-GEOD-41364 | biostudies-arrayexpress