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SRP103009
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2000
Description
The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that is commonly deregulated in human diseases. Here we find that mTORC1 controls a transcriptional program encoding amino acid transporters and metabolic enzymes through a mechanism also used to regulate protein synthesis. Bioinformatic analysis of mTORC1-responsive mRNAs identified a promoter element recognized by activating transcription factor 4 (ATF4), a key effector of the integrated stress response. ATF4 translation is normally induced by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2a) through a mechanism that requires upstream open reading frames (uORFs) in the ATF4 5'' UTR. mTORC1 also controls ATF4 translation through uORFs, but independent of changes in eIF2a phosphorylation. mTORC1 instead employs the 4E-binding protein (4E-BP) family of translation repressors. These results link mTORC1-regulated demand for protein synthesis with an ATF4-regulated transcriptional program that controls the supply of amino acids to the translation machinery. Overall design: RNA-seq analysis of wild-type and ATF4-null HEK293T cells treated with Torin 1 or tunicamycin for 6 h, and ribosome profiling analysis of HEK293T cells treated with Torin 1 for 24 h.
Publication Title
mTORC1 Balances Cellular Amino Acid Supply with Demand for Protein Synthesis through Post-transcriptional Control of ATF4.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina Genome Analyzer II
Description
Ribsome profiling analysis of mRNA translation in mouse cells under conditions of mTOR activiation or inhibition. Overall design: embryonic fibroblasts from 4EBP1/2 p53 mutants treated with Torin1
Publication Title
A unifying model for mTORC1-mediated regulation of mRNA translation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
Skeletal muscle of insulin resistant individuals is characterized by lower fasting lipid oxidation and reduced ability to switch between lipid and glucose oxidation. The purpose of the present study was to examine if impaired metabolic switching could be induced by chronic hyperglycemia. Human myotubes were treated with or without chronic hyperglycemia (HG) (20 mmol/l glucose for 4 days), and the metabolism of [14C]oleic acid (OA) and [14C]glucose was studied. Acute glucose (5mmol/l) suppressed OA oxidation by 50% in normoglycemic (NG) (5.5 mmol/l glucose) cells. Myotubes exposed to chronic hyperglycemia showed a significantly reduced OA uptake and oxidation to CO2, whereas acid-soluble metabolites were increased. Glucose suppressibility, the ability of acute glucose to suppress lipid oxidation, was significantly reduced to 21%, while adaptability, the capacity to increase lipid oxidation with increasing fatty acid availability, was unaffected. Glucose uptake and oxidation was significantly reduced by about 40%. Substrate oxidation in presence of mitochondrial uncouplers showed that net and maximal oxidative capacities were significantly reduced after hyperglycemia, and the concentration of ATP was reduced by 25%. However, none of the measured mitochondrial genes were downregulated nor was mitochondrial content. Microarray showed that no genes were significantly regulated by chronic hyperglycemia. Addition of chronic lactate reduced both glucose and OA oxidation to the same extent as hyperglycemia, and this effect was specific for lactate. In conclusions, chronic hyperglycemia reduced substrate oxidation in skeletal muscle cells and impaired the metabolic switching. The effect is most likely due to an induced mitochondrial dysfunction.
Publication Title
Chronic hyperglycemia reduces substrate oxidation and impairs metabolic switching of human myotubes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In this experiment, mucous neck cells from the gastric epithelium of normal, adult C57/B6 mice were laser-capture microdissected to determine gene expression in neck cells relative to pit cells, parietal cells, and zymogenic cells, whose expression profiles were previously deposited in GEO.
Publication Title
Evolution of the human gastrokine locus and confounding factors regarding the pseudogenicity of GKN3.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) upon glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions.
Publication Title
Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The role of peroxisome proliferator-activated receptor (PPAR) activation on global gene expression and mitochondrial fuel utilization were investigated in human myotubes. Only 21 genes were up-regulated and 3 genes were down-regulated after activation by the PPAR agonist GW501516. Pathway analysis showed up-regulated mitochondrial fatty acid oxidation, TCA cycle and cholesterol biosynthesis. GW501516 increased oleic acid oxidation and mitochondrial oxidative capacity by 2-fold. Glucose uptake and oxidation were reduced, but total substrate oxidation was not affected, indicating a fuel switch from glucose to fatty acid. Cholesterol biosynthesis was increased, but lipid biosynthesis and mitochondrial content were not affected. This study confirmed that the principal effect of PPAR activation was to increase mitochondrial fatty acid oxidative capacity. Our results further suggest that PPAR activation reduced glucose utilization through a switch in mitochondrial substrate preference by up-regulating pyruvate dehydrogenase kinase isozyme 4 and genes involved in lipid metabolism and fatty acid oxidation.
Publication Title
PPARδ activation in human myotubes increases mitochondrial fatty acid oxidative capacity and reduces glucose utilization by a switch in substrate preference.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 196 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on peripheral blood mononuclear cells (PBMC) gene expression. We studied obese adults with features of the metabolic syndrom, n=66. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks.
Publication Title
Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome: a SYSDIET sub-study.
Sample Metadata Fields
Age, Time
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to downregulate NF-B; a major contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the observed effects. The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, actual skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting. Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways (e.g.IL-17A, IL-17F,IL-23p19 ). Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis. In conclusion, resveratrol ameliorates psoriasis, and changes in expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner suggests it might have a role in the treatment of psoriasis and should be explored further in a human setting.
Publication Title
Resveratrol ameliorates imiquimod-induced psoriasis-like skin inflammation in mice.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Studies have shown that vitamin D can enhance glucose-stimulated insulin secretion (GSIS) and change the expression of genes in pancreatic β-cells. Still the mechanisms linking vitamin D and GSIS are unknown.
Publication Title
Vitamin D metabolites influence expression of genes concerning cellular viability and function in insulin producing β-cells (INS1E).
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 70 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
We construced combinations of genetic deletions to infer genetic interactions in genomic expression data.
Publication Title
Prediction of phenotype and gene expression for combinations of mutations.
Sample Metadata Fields
No sample metadata fields
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