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GSE15129
Mus musculus
72 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Our present study reveals significant decelerating effects on senescence processes in middle-aged SAMP1 mice supplemented for 6 or 14 months with the reduced form (QH2, 500 mg/ kg BW/ day) of coenzyme Q10 (CoQ10). To unravel molecular mechanisms of these CoQ10 effects, a genome-wide transcript profiling in liver, heart, brain and kidney of SAMP1 mice supplemented with the reduced (QH2) or oxidized form of CoQ10 (Q10) was performed. Liver seems to be the main target tissue of CoQ10 intervention, followed by kidney, heart and brain. Stringent evaluation of the resulting data revealed that QH2 has a stronger impact on gene expression than Q10, which was primarily due to differences in the bioavailability. Indeed, we found that QH2 supplementation was more effective than Q10 to increase levels of CoQ10 in the liver of SAMP1 mice (54.92-fold and 30.36-fold, respectively). To identify functional and regulatory connections of the top 50 (p < 0.05) up- and down-regulated QH2-sensitive transcripts in liver (fold changes ranging from 21.24 to -6.12), text mining analysis (Genomatix BiblioSphere, GFG level B3) was used. Hereby, we identified 11 QH2-sensitive genes which are regulated by PPAR- and are primarily involved in cholesterol synthesis (e.g. HMGCS1, HMGCL, HMGCR), fat assimilation (FABP5), lipoprotein metabolism (PLTP) and inflammation (STAT-1). Thus, we provide evidence that QH2 is involved in the reduction of fat and cholesterol synthesis via modulation of the PPAR- signalling pathway. These data may explain, at least in part, the observed effects on decelerated age-dependent degeneration processes in QH2-supplemented SAMP1 mice.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Colorectal cancer (CRC) is still one of the most common causes of cancer-related death worldwide (World Health Organization, Fact sheet N297, October 2011). Though, therapeutic options improved over the past years, the prognosis of metastatic colorectal cancer (mCRC) remains poor with a median survival of 18-21 months.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Monocytes are key players in inflammatory processes which are triggered by lipopolysaccharide (LPS), the major outer membrane component of gram-negative bacteria. The present study in human monocytic THP-1 cells was designed in order to identify LPS-inducible genes which are down-regulated by the reduced form of CoQ10 (ubiquinol, Q10H2). For this purpose, THP-1 cells were incubated with 10 M Q10H2 for 24 h. Subsequently, cells were stimulated for 4 h with 1g/ml LPS and the resulting gene expression levels were determined using microarrays. 14 LPS-inducible genes were identified to be significantly (p < 0.05) down-regulated by Q10H2 pre-treatment between a factor of 1.32 and 1.65. The strongest effect of Q10H2 incubation was found for the nuclear receptor coactivator 2 gene (NCOA2). Gene Ontology (GO) terms revealed for the Q10H2-sensitive genes an involvement in e.g. signal transduction processes (CENTD1, NCOA2, PSD3, PPP2R5C), transcriptional regulation (NCOA2, POU2F1, ETV3) and cell proliferation pathways (CCDC100, EPS15). In conclusion, we provide evidence in THP-1 cells that the reduced form of CoQ10 (Q10H2) modulates LPS-induced gene expression.
Publication Title
The reduced form of coenzyme Q10 decreases the expression of lipopolysaccharide-sensitive genes in human THP-1 cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Coenzyme Q10 (CoQ10) is an obligatory element in the respiratory chain and functions as a potent antioxidant of lipid membranes. More recently, anti-inflammatory effects as well as an impact of CoQ10 on gene expression have been observed. To reveal putative effects of Q10 on LPS-induced gene expression, whole genome expression analysis was performed in the monocytic cell line THP-1. 1129 probe sets have been identified to be significantly up-regulated (p < 0.05) in LPS-treated cells when compared to controls. Text mining analysis of the top 50 LPS up-regulated genes revealed a functional connection in the NFB pathway and confirmed our applied in vitro stimulation model. Moreover, 33 LPS-sensitive genes have been identified to be significantly down-regulated by Q10-treatment between a factor of 1.32 and 1.85. GeneOntology (GO) analysis revealed for the Q10-sensitve genes a primary involvement in protein metabolism, cell proliferation and transcriptional processes. Three genes were either related to NFB transcription factor activity, cytokinesis or modulation of oxidative stress. In conclusion, our data provide evidence that Q10 down-regulates LPS-inducible genes in the monocytic cell line THP-1. Thus, the previously described effects of Q10 on the reduction of pro-inflammatory mediators might be due to its impact on gene expression.
Publication Title
Identification of LPS-inducible genes downregulated by ubiquinone in human THP-1 monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in vitro and in mice indicate a role for Coenzyme Q10 (CoQ10) in gene expression. To determine this function in relationship to physiological readouts, a 2-week supplementation study with the reduced form of CoQ10 (ubiquinol, Q10H2, 150 mg/d) was performed in 53 healthy males. Mean CoQ10 plasma levels increased 4.8-fold after supplementation. Transcriptomic and bioinformatic approaches identified a gene-gene interaction network in CD14-positive monocytes, which functions in inflammation, cell differentiation and PPAR-signaling. These Q10H2-induced gene expression signatures were also described previously in liver tissues of SAMP1 mice. Biochemical as well as NMR-based analyses showed a reduction of LDL cholesterol plasma levels after Q10H2 supplementation. This effect was especially pronounced in atherogenic small dense LDL particles (19-21 nm, 1.045 g/l). In agreement with gene expression signatures, Q10H2 reduces the number of erythrocytes but increases the concentration of reticulocytes. In conclusion, Q10H2 induces characteristic gene expression patterns, which are translated into reduced LDL cholesterol levels and erythropoiesis in humans.
Publication Title
Ubiquinol-induced gene expression signatures are translated into altered parameters of erythropoiesis and reduced low density lipoprotein cholesterol levels in humans.
Sample Metadata Fields
Sex, Disease, Disease stage
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Quercetin has been described to have a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reduced risk of cardiovascular disease. We tested whether a daily supplementation of quercetin leads to reproducible changes in gene expression profiles of human monocytes.
Publication Title
Quercetin supplementation and its effect on human monocyte gene expression profiles in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer is one of the most common causes of cancer-related deaths worldwide. The lymph node status represents the strongest prognostic factor. Due to its extremely poor prognosis, the identification of novel therapeutic targets is urgently needed. Therefore, we aimed to assess differentially expressed genes in nodal negative versus nodal positive intestinal type gastric carcinoma by GeneChip array technique. The transcriptional profile of 6 gastric cancers with and without lymphatic dissemination was analyzed. A total of 115 transcripts were found to be up- and 219 to be down-regulated in node positive compared with node negative gastric cancers. Next we searched for differentially expressed GPCRs. We identified 52 GPCRs and GPCR-related genes, which were up- or down-regulated with a fold change factor greater 1.5.
Publication Title
Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer?
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-B, e.g. TNFAIP3 (A20) and IER3.
Publication Title
Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling regulates a variety of developmental cell fates decisions in a cell-context dependent manner. Although Notch signaling directly regulates transcription via the RBP-J/CSL DNA binding protein, little is known about the genes in the respective tissues that are directly activated by Notch.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
ClC-2 is a broadly expressed Cl- channel of the CLC family of Cl- channels and transporters which is abundantly expressed in brain. Here it was proposed to participate in lowering the cytoplasmic Cl- concentration of neurons, a process that establishes an inhibitory response to the neurotransmitters GABA and glycine (Staley et al., 1996). Heterozygous mutations in CLCN2 (the gene encoding ClC-2) were recently reported in a few patients with three clinically distinct forms of epilepsy (Haug et al, 2003). However, the disruption of ClC-2 in mice (ClC-2 KO mouse) did not entail epilepsy (Bösl et al., 2001; Nehrke et al., 2002) but myelin vacuolation in fiber tracts of the central nervous system. We used a gene expression profiling of the ClC-2 KO mouse in brain to identify possible disease mechanism which cause the observed myelin phenotype. As these myelin vacuolation became apparent in the fiber tracts of ClC-2 KO cerebellum at P28 and increased with age, we analysed the cerebellum of ClC-2 KO mice at different postnatal ages, before (P14) and after (P35) the KO cerebellum has been affected by myelin vacuolation.
Publication Title
Leukoencephalopathy upon disruption of the chloride channel ClC-2.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples