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GSE49817
Homo sapiens
18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study determined the genes that are differetially expressed when regulatory T cells were stimulated in vitro with IL-2
Publication Title
Selective IL-2 responsiveness of regulatory T cells through multiple intrinsic mechanisms supports the use of low-dose IL-2 therapy in type 1 diabetes.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Objective: identify novel and relevant aspects of Sorafenib action on liver cancer cells. We found that in rat hepatocholangiocarcinoma (LCSC-2) cells, exposure to the MEK/multikinase inhibitor sorafenib did not inhibit ERK phosphorylation nor induced appreciable cell death in the low micromolar range; instead, the drug elicited a raise of intracellular reactive oxygen species (ROS) accompanied by a severe decrease of oxygen consumption and intracellular ATP levels, all changes consistent with mitochondrial damage. Moreover, Sorafenib induced depolarization of isolated rat liver mitochondria, indicating a possible direct effect on the organelle. Microarray analysis of gene expression in sorafenib-trated cells revealed a metabolic reprogramming toward aerobic glycolysis, that likely accounts for resitance to drug toxicity in this cell line. Importantly, cytotoxicity was strongly potentiated by glucose withdrawal from the culture medium or by the glycolytic inhibitor 2-deoxy-glucose, a finding also confirmed in the highly malignant melanoma cell line B16F10. Mechanistic studies revealed that ROS are pivotal to cell killing by the Sorafenib + 2DG combination, and that a low content of intracellular oxidants is associated with resistance to the drug; instead, Thr172phosphorylation/activation of the AMP-activated protein kinase (AMPK), induced by Sorafenib, may exert protective effects, since cytotoxicity was enhanced by an AMPK specific inhibitor and prevented by the AMPK activator Metformin. Overall, this study identifies novel and relevant aspects of Sorafenib action on liver cancer cells, including mitochondrial damage, induction of ROS and a metabolic cell reprogramming towards glucose addiction, potentially exploitable in therapy.
Publication Title
The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mitochondrial DNA (mtDNA) mutations may contribute to aging and age-related disorders. Previously, we created mice expressing a proofreading-deficient version of the mtDNA polymerase gamma (Polg) which accumulate age-related mtDNA mutations and display premature aging. Here we performed microarray gene expression profiling to identify mtDNA mutation-responsive genes in the cochlea of aged mitochondrial mutator mice. Age-related accumulation of mtDNA mutations was associated with transcriptional alternations consistent with reduced inner ear function, mitochondrial dysfunction, neurodegeneration, and reduced cell structural modulation. Hearing assessment and histopathological results confirmed that aged PolgD257A/D257A (D257A) mice exhibited moderate hearing loss and severe cochlear degenerations. Age-related accumulation of mtDNA mutations also resulted in alternations in gene expression consistent with induction of apoptosis, proteolysis, stress response, and reduced DNA repair. TUNEL (Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) assay confirmed that the cochleae from aged D257A mice showed significantly more TUNEL positive cells compared to wild-type (WT) mice. The levels of cleaved caspase-3 were also found to increase in the cochleae of aged D257A mice. These observations provide evidence that age-related accumulation of mtDNA mutations is associated with apoptotic cell death in aged cochlea. Our results provide the first global view of molecular events associated with mtDNA mutations in postmitotic tissue, and suggest that apoptosis is the major mechanism of mtDNA mediated cell death in the development of age-related hearing disorder.
Publication Title
The role of mtDNA mutations in the pathogenesis of age-related hearing loss in mice carrying a mutator DNA polymerase gamma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
PAD4 is overexpressed in many cancer cells. We developed PAD inhibitors that efficiently inhibit the cancer cell growth. One inhibitor YW3-56 could efficently induce cell death of triple negative breast cancer MDA-MB-231 cells.
Publication Title
ATF4 Gene Network Mediates Cellular Response to the Anticancer PAD Inhibitor YW3-56 in Triple-Negative Breast Cancer Cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
Illumina HiSeq 2500
Description
Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with its Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing at the Mediator level. In sum, we provide insight into how NPC-associated adaptor complexes can access the core transcription machinery. Overall design: RNAseq was performed from WT, sac3?, cdk8? and Sac3 R288D mutant cells. For each strain triplicates were analyzed. WT strain was sac3? transformed with pRS315 SAC3 WT
Publication Title
The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 448 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 112 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The effect of a short-term calorie restricted diet was evaluated in heart in seven strains of mice
Publication Title
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 112 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The effect of a short-term calorie restricted diet was evaluated in gastrocnemius muscle (GASTROC) in seven strains of mice
Publication Title
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 112 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The effect of a short-term calorie restricted diet was evaluated in epididymal white adipose tissue (WAT) in seven strains of mice
Publication Title
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 112 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The effect of a short-term calorie restricted diet was evaluated in cerebral cortex in seven strains of mice
Publication Title
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sample Metadata Fields
Sex, Specimen part
View Samples