Gene expression analyses were carried out to identify genes regulated by 17-beta estradiol (E2) and Hydroxytamoxifen (OHT) through GPR30 in SKBR3 cells, a breast cancer cell-line which expresses GPR30 but lacks Estrogen Receptor alpha or beta.
Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF.
No sample metadata fields
View SamplesNon-steroidal anti-inflammatory drugs, principally aspirin (acetylsalicylic acid, ASA), have anti-neoplastic properties, as shown by epidemiological studies on colorectal cancer and many other types of tumours. The chemopreventive and anti-proliferative properties of aspirin towards tumour cells have been shown to be due to the induction of programmed cell death such as apoptosis. Yeast cells are among the experimental models used extensively for the study of oxidative stress and apoptosis in living organisms because yeast, such as S. cerevisiae, retains many of the core eukaryotic cellular processes, including the hallmarks of eukaryotic apoptosis. An important contribution of our previous work has been the clarification of the critical defensive role of the antioxidant mitochondrial enzyme manganese superoxide dismutase (MnSOD) against apoptosis, confirmed to be the attenuation of aspirin-induced superoxide radical accumulation in the yeast mitochondria (Farrugia et al. (2013) FEMS Yeast Res 13, 755-768). To study the possible differential expression of gene transcripts in relation to the induction of apoptosis by aspirin, we used gene expression profiling by means of GeneChip Microarray Technology (Affymetrix). The yeast strains considered for this study included (1) the wild type strain S. cerevisiae EG103, which contains both MnSOD and cytosolic copper, zinc superoxide dismutase (CuZnSOD) and (2) the redox-compromised MnSOD-deficient S. cerevisiae EG110 strain. [This work was financed by the Malta Council for Science and Technology through the R&I Technology Development Programme (Project R&I-2015-001)].
Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells.
No sample metadata fields
View SamplesCaspase-1 activation senses metabolic danger-associated molecular patterns and mediates the initiation of inflammation. Here, we reported that caspase-1 contributes to hyperlipidemia-induced modulation of vascular cell gene expression during early atherosclerosis in vivo. Our results demonstrate the therapeutic potential of caspase-1 inhibition in the treatment of cardiovascular diseases.
Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation.
Sex, Age, Specimen part
View SamplesExposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
Erbb2 regulates inflammation and proliferation in the skin after ultraviolet irradiation.
No sample metadata fields
View SamplesEstrogen receptors (ERs), which mediate the proliferative action of estrogens in breast cancer cells, are ligand-dependent transcription factors that regulate expression of their primary target genes through several mechanisms. In addition to direct binding to cognate DNA sequences, ERs can be recruited to DNA through other transcription factors (tethering), or affect gene transcription through modulation of signaling cascades by non-genomic mechanisms of action. To better characterize the mechanisms of gene regulation by estrogens, we have identified more than 700 putative primary and more than 1500 putative secondary target genes of estradiol in MCF7 cells through microarray analysis performed in the presence or absence of the translation inhibitor cycloheximide.
Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells.
No sample metadata fields
View SamplesGenome-wide gene expression was measured in peripheral blood mononuclear cells (PBMCs) from patients with cystic fibrosis (CF) after treatment in vitro with the flagellin protein fliC, and/or synthetic peptide IDR-1018 to assess patterns of gene expression. The patterns of gene expression suggest that CF cells have a hyperinflammatory phenotype including dysfunctional autophagy processes. The synthetic peptide IDR-1018 attentuates this hyperinflammatory phenotype. Overall design: Total RNA was obtained from PBMCs obtained from CF patients after treatment with the fliC flagellin protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.
Rescue of dysfunctional autophagy attenuates hyperinflammatory responses from cystic fibrosis cells.
Specimen part, Treatment, Subject
View SamplesHuman subjects were randomized for treatment with a GnRH-analogue, Goserelin, which suppresses endogenous testosterone or placebo for 12 weeks. Strength training was performed during the last 8 weeks. The suppression of testosterone resulted in an attenuation of the normal muscle adaptation to strength training (increased muscle mass and strength). To identify molecular signals involved in the response to testosterone levels, biopsies were obtained 4 hours after the last training session and gene expression compared with Affymetrix 3' microarrays. This timepoint should capture goserelin effect on both constitutive expression, training induced changes as well as acute exercise induced (4 hours) differences in mRNA levels.
The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels.
Sex, Age, Specimen part, Treatment
View SamplesmRNA sequencing was used to identify genome wide transcriptional changes occuring in fly heads in response to spermidine feeding. This study shed light on the molecular mechanisms through wich spermidine can protect against age-dependent memory impairment. Overall design: mRNA profiles from 3 and 10 day old Drosophila melanogaster heads were generated in duplicate by deep sequencing using Illumina GAIIx. mRNA profiles from flies that were fed food with 5mM spermidine were compared to profiles from flies that had no spermidine in thier food.
Restoring polyamines protects from age-induced memory impairment in an autophagy-dependent manner.
Age, Specimen part, Subject
View SamplesU.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.
Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.
Specimen part, Treatment
View SamplesWe applied RNA sequencing (RNA-seq) to map the global changes in gene expression of interscapular brown adipose tissue (iBAT) of mice subjected to acute cold exposure for 3 days. Here we find extensive changes in the iBAT transcriptome in response to cold with a prominent induction of genes associated to lipid-related metabolic processes. Overall design: RNA-seq of poly-A enriched RNA isolated from brown adipose tissue of 5 mice housed at room temperature (22°C) and 5 mice exposed to cold (4°C) for 3 days.
RNA-Seq and Mass-Spectrometry-Based Lipidomics Reveal Extensive Changes of Glycerolipid Pathways in Brown Adipose Tissue in Response to Cold.
No sample metadata fields
View Samples