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GSE56426
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The role of innate immunity in modulating severity of chemotherapy-induced complications is so far unclear. The aim of this study was to determine how TLR2 may influence MTX-induced mucositis in the small intestine in mice. We used microarrays to assess gene expression profiles in proximal jejunum of WT vs. TLR2 KO mice after systemic treatment with MTX.
Publication Title
TLR signaling modulates side effects of anticancer therapy in the small intestine.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 20 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Recent evidence supports a role for RNA as a common pathogenic agent in both the polyglutamine and untranslated dominant expanded repeat disorders. One feature of all repeat sequences currently associated with disease is their predicted ability to form a hairpin secondary structure at the RNA level. In order to investigate mechanisms by which hairpin forming repeat RNAs could induce neurodegeneration, we have looked for alterations in gene transcripts as hallmarks of the cellular response to toxic hairpin repeat RNAs. Three disease associated repeat sequences - CAG, CUG and AUUCU - were specifically expressed in the neurons of Drosophila and resultant common, early, transcriptional changes assessed by microarray analyses. Transcripts that encode several components of the Akt/Gsk3- signalling pathway were altered as a consequence of expression of these repeat RNAs, indicating that this pathway is a component of the neuronal response to these pathogenic RNAs and may represent an important common therapeutic target in this class of diseases.
Publication Title
Perturbation of the Akt/Gsk3-β signalling pathway is common to Drosophila expressing expanded untranslated CAG, CUG and AUUCU repeat RNAs.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Methionine adenosyltransferase (MAT) enzymes generate SAMe (S-adenosylmethionine), the main biological methyl donor. There are two MAT encoding genes in mammals (Mat1a and Mat2a), which show different activities and cellular distribution. Mat1a encodes the enzyme mainly expressed in normal liver. Mat1a ablation in mice results in the spontaneous development of non-alcoholic steatohepatitis (NASH). We observed that SAMe depletion in Mat1a KO mice had three main effects on hepatic lipid metabolism: 1) impaired TG (triglyceride) export via VLDL; 2) impaired mitochondrial FA (fatty acid) oxidation (as evidenced by membrane depolarization, downregulation of Phb1 (prohibitin 1, a mitochondrial chaperone protein) and Mcj/Dnajc15 (endogenous mitochondrial repressor of respiratory chain), and accumulation of long-chain acylcarnitines); and 3) increased FA uptake. The convergence of these three factors induced TG accumulation in LD (lipid droplets). LD expansion confronts hepatocytes with a high demand of PC (phosphatidylcholine) molecules to cover the LD surface since other phospholipids, such as PE (phosphatidylethanolamine), cannot stabilize LD and prevent coalescence. In Mat1a KO this situation is aggravated, since SAMe-dependent PC synthesis via PE methylation is decreased, the PC/PE ratio reduced and mitochondrial FA oxidation impaired. To put a brake to this drain of PC molecules to LD, FA are rerouted in Mat1a KO mice liver to other catabolic (endoplasmic reticulum and peroxisome oxidation) and biosynthetic (ceramides synthesis) pathways, causing oxidative stress, inflammation and fibrosis. SAMe treatment for two months in 8-9 month old Mat1a KO mice ameliorated mitochondrial dysfunction (reduces membrane depolarization, improves Phb1 and Mcj expression, and increases SAMe transport to mitochondria) improving FA oxidation efficiency (FA and acylcarnitine levels decrease), which results in a drastic reduction in TG accumulation. SAMe treatment in Mat1a KO mice resulted in more PC available for proper membrane function, improving liver lipid homeostasis, histology (H&E, Sudan red, Sirius red) and liver injury (ALT, AST).
Publication Title
Metabolomic Identification of Subtypes of Nonalcoholic Steatohepatitis.
Sample Metadata Fields
Age, Specimen part
View Samples