Whole genome analysis regulation in HepG2 cells exposed to cadmium
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: marco fabbri
PROVIDER: E-GEOD-31286 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:BACKGROUND: Cadmium (Cd) is implicated in prostate carcinogenesis but its oncogenic action remains unclear. OBJECTIVES: This study aims to decipher changes in cell growth and the transcriptome in an immortalized human normal prostate epithelial cell line (NPrEC) following exposure to low-dose Cd. METHODS: Synchronized NPrEC cells were exposed to different doses of Cd and assayed for cell viability and cell-cycle progression. Temporal changes in transcriptome were investigated by global profiling. Ingenuity Pathways Analyses were used to develop propositions about functional connections among differentially expressed genes. A neutralizing antibody was used to negate the effect of Cd-induced upregulation of TNF in NPrEC. RESULTS: Exposure of NPrEC to 2.5 microM of Cd enhanced cell viability and accelerated cell-cycle progression. Global expression profiling identified 48 genes that exhibited â?¥1.5-fold changes in expression after 4, 8, 16 and 32 hr of Cd treatment. Pathway analyses inferred a functional connection among 35 of these genes in one major network with TNF as the most prominent node. Fourteen out of the 35 genes in the network are related to TNF with 11 exhibited an average of â?¥2-fold changes in gene expression. Real-time RT-PCR confirmed the upregulation of 7 of the 11 genes (ADAM8, EDN1, IL8, IL24, IL13RA2, COX2/PTGS2 and SERPINB2) and uncovered a 28-fold transient increase in TNF expression in Cd-treated NPrEC. A TNF-neutralizing antibody effectively blocked Cd-induced elevations in the expression of these genes. CONCLUSIONS: Non-cytotoxic, low-dose Cd has growth-promoting effects on NPrEC and induces transient overexpression of TNF, leading to upregulation of genes with oncogenic and immunomodulation functions. Experiment Overall Design: A total of 19 samples were analyzed, each experimental condition having two biological replicates, except Cadmium 4hr which has only 1 sample. Cadmium-treated and control samples were taken at 0, 4, 8, 16, and 32 hours.
2008-04-06 | E-GEOD-9951 | biostudies-arrayexpress
Project description:The transcriptomic changes induced in the human liver cell line HepG2 by 100M-BM-5M menadione, 200M-BM-5M TBH or 50M-BM-5M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h. The study investigated differential gene expression in HepG2 cell line mRNA following 0.5, 1, 2, 4, 6, 8 and 24h hours of exposure to 100M-BM-5M menadione, 200M-BM-5M TBH or 50M-BM-5M H2O2 and medium without compound. Three biological replicates per compound/solvent. In total 126 arrays.
2013-05-31 | E-GEOD-39291 | biostudies-arrayexpress
Project description:DNA microarray analysis revealed that the genes related to cell cycle regulation were significantly induced at non- and sub-lethal concentrations (i.e., 0.05-6 M-BM-5M), while the common feature of heavy metal toxicity such as oxidative damage and following increase in glutathione, heat shock proteins, and metallothionein were confirmed at high concentrations (i.e., 6-40 M-BM-5M). The concentration dependent modulation of gene expression (induction of cell cycle genes, induction of cell cycle arrest genes and apoptotic genes) following exposure to arsenic was further supported by acceleration of cell proliferation, ROS generation, and cytotoxicity. Furthermore, three cell cycle genes (i.e., CDC25B, UBE2C, and PTTG1) were proposed as marker genes of inorganic arsenic exposure. Those results indicated the potential pro-carcinogenic actions of inorganic arsenic occur in environmentally relevant exposures (as low as 0.07 M-BM-5M). In this study, we examined the gene expression alteration in HepG2 cells exposed to arsenic trioxide (5 nM to 40 M-BM-5M as As2O3 for 48 hours) by DNA microarray with 8795 human genes. HepG2 cells were also exposed to M-NM-5-caprolactam as a reference of non carcinogen since it is the only chemical categorized in IARCM-bM-^@M-^Ys group 4 (Probably Not Carcinogenic). MQ water was used as control. For replicate, three dishes were prepared for each sample and individually treated in parallel.
2013-07-02 | E-GEOD-48441 | biostudies-arrayexpress
Project description:We investigated the impact of cadmium on the global transcriptome of E. coli wild type, â??gshA and â??gshB mutant cells to evaluate the molecular basis of cadmium toxicity in the presence or absence of cellular thiols. This global transcriptome analysis were done with cells synthezising GSH (wild type), gamma-glutamyl-cysteine (â??gshB mutant) or neither of the two cellular thiols (â??gshA mutant) under the influence of 100 µM Cd(II). E. coli cells, wild type, â??gshA and â??gshB mutant strain, were grown at 37 °C . At a cell turbidity of 100 Klett, cells were treated for 10 min with 100 µM Cd(II) or no metal as a control in TMM medium. Total RNA was extracted, DNAse digested and reverse-transcribed with either Cy3- or Cy5-labeled dCTP. Both labeled cDNA were hybridized to a slide at 42 °C. All experiments were performed with three independent biological repeats.
2008-05-31 | E-GEOD-11562 | biostudies-arrayexpress
Project description:The only group of organisms in which a biological function for cadmium has been shown is the diatoms, which are unicellular phytoplankton. Yet diatoms exhibit similar sensitivity to Cd as other groups of phytoplankton. We have investigated responses of Cd on molecular, metabolic and physiological levels in the diatom Phaeodactylum tricornutum. P. tricornutum apparently has a high tolerance to Cd; only minor responses were observed on growth, pigment and transcriptional changes at cadmium concentrations of 123 µg/l. No significant changes in chlorophyll and xanthophyll levels were observed, and the very few transcripts affected strongly indicate that the cells were able to respond to the increased Cd2+ levels without changing proteins levels. At 10 times this concentration, 1230 µg/l, a much clearer response was observed, including transcripts encoding proteins involved in metal transport, cell signalling and detoxification processes. Our results point towards putative pathways for the removal or detoxification of Cd and its metabolites, as well as a possible Cd uptake mechanism. We predict that ATPase5-1B is involved in removal of Cd by pumping Cd2+ ions out of the cell, whereas VIT1/CCC1 sequesters Cd2+ in the vacuole. Cultures of Phaeodactylum tricornutum were treated with two concentrations of Cd2+, 123 µg/l and 1230 µg/l. The reference samples were grown in artificial seawater base AK modified with added f/2-medium nutrients. Three biological replicates were harvested for all samples.
2011-08-01 | E-GEOD-31131 | biostudies-arrayexpress
Project description:Many heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays. We identified both common and unique biological responses to exposure to the three metals. Nickel, cadmium, chromium all induced oxidative stress with both similar and unique genes and pathways responding to this stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure, perhaps by replacing iron in key proteins. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells. H4-II-E-C3 cells were were exposed to nickel (II) chloride (NiCl2), cadmium chloride (CdCl2), or sodium dichromate (Na2Cr2O7) for 24 hours. The cells were treated with a low, mid, and high concentration of each chemical and shared a control for each biological replicated, and we exposed 4 biologcial replicates for a total of 44 samples.
2011-08-18 | E-GEOD-31503 | biostudies-arrayexpress
Project description:The transcriptomic changes induced in the human liver cell line HepG2 by 7M-BM-5M of cisplatin after treatment for 12, 24 and 48h The study investigated differential gene expression in HepG2 cell line mRNA following 12,24 and 48 hours of exposure to 7M-BM-5M of cisplatin and its solvent. Three biological replicates per compound/solvent. In total 18 arrays .
2013-12-05 | E-GEOD-38122 | biostudies-arrayexpress
Project description:An 8X15k oligonucleotide microarray was developed consisting of 2334 E. glacialis probes and 2166 Tursiops truncatus probes and used to measure the transcriptome level effects of right whale kidney fibroblast cells exposed to cadmium. Cells were exposed to three concentrations of cadmium chloride (CdCl2) for three exposure times. Cells exposed to 10-6M CdCl2 for 4 hours and 24 hours showed upregulated genes involved in protection from metal toxicity, oxidative stress, protein renaturation, apoptosis inhibition, and several regulators of cellular processes. Downregulated genes represented a suite of functions including cell proliferation, transcription regulation, actin polymerization, and stress fiber synthesis. The collection of differentially expressed genes in this study support proposed mechanisms of cadmium-induced apoptosis such as mitochondrial membrane potential collapse, reactive oxygen species (ROS) influx, and cell cycle arrest. The results confirm the right whale microarray as a reproducible tool in measuring differentiated gene expression and should be a valuable asset for transcriptome analysis of other baleen whales and potential health assessment protocols. 35 Samples were analyzed representing 3 biological replicates for each treatment and corresponding controls except treatment 4hour_0.01uMCdCl2 had only two biological replicates due to spot intensity values. There are 3 spot replicates/probe on the array, along with Agilent control grid specific for 8X15K arrays, and 4 Karenia brevis sequences used as a negative control (K.brevis.chlorophyllA/Bbindingprotein, K.brevis.flavodoxin,K.brevis.photolyase,K.brevis.photosystemcoreprotein).
2009-08-03 | E-GEOD-17457 | biostudies-arrayexpress
Project description:Several metals are essential nutrients for plants but metals are toxic in excess, deleteriously affecting crop yield and quality. Various kinds of genes involved in metal homeostasis have been investigated in detail over the past few decades and the mechanisms of how metals are absorbed from soil and distributed in plants have been elucidated. However, numerous genes related to metal homeostasis remain to be investigated and a comprehensive analysis of the expressions of these genes is required. In the present study, we investigated the spatial gene expression profile of iron (Fe)-deficient and cadmium (Cd)-stressed rice by a combination of laser capture microdissection and microarray analysis. We performed comprehensive microarray analysis of a rice root using laser microdissection and collected a total of 13 samples (3 replicates for each sample, 39 total microarray data). Roots of normal, Fe-deficient (-Fe) and Cd-stressed (+Cd) rice were separated into the vascular bundle (VB), cortex (Cor), and epidermis plus exodermis (EP). In addition, vascular bundles from new leaves (newDC) and old leaves (oldDC) at the lowest node, which are important for metal distribution, were separately analyzed.
2013-12-31 | E-GEOD-40549 | biostudies-arrayexpress
Project description:Thermococcus gammatolerans, the most radioresistant archaeon known to date, is an anaerobic and hyperthermophilic sulfur-reducing organism living in deep-sea hydrothermal vents. Knowledge of mechanisms underlying archaeal metal tolerance in such metal-rich ecosystem is still poorly documented. We showed that T. gammatolerans exhibits high resistance to cadmium (Cd), cobalt (Co) and zinc (Zn), a weaker tolerance to nickel (Ni), copper (Cu) and arsenate (AsO4) and that cells exposed to 1mM Cd exhibit a cellular Cd concentration of 66M-BM-5M. A time-dependent transcriptomic analysis using microarrays was performed at a non-toxic (100M-NM-<M) and a toxic (1mM) Cd dose. The reliability of microarray data was strengthened by real time RT-PCR validations. Altogether, 114 Cd responsive genes were revealed and a substantial subset of genes is related to metal homeostasis, drug detoxification, re-oxidization of cofactors and ATP production. This first genome-wide expression profiling study of archaeal cells challenged with Cd showed that T. gammatolerans withstands induced stress through pathways observed in both prokaryotes and eukaryotes but also through new and original strategies. T. gammatolerans cells challenged with 1mM Cd basically promote: 1) the induction of several transporter/permease encoding genes, probably to detoxify the cell; 2) the upregulation of Fe transporters encoding genes to likely compensate Cd damages in iron-containing proteins; 3) the induction of membrane-bound hydrogenase (Mbh) and membrane-bound hydrogenlyase (Mhy2) subunits encoding genes involved in recycling reduced cofactors and/or in proton translocation for energy production. By contrast to other organisms, redox homeostasis genes appear constitutively expressed and only a few genes encoding DNA repair proteins are regulated. We compared the expression of 27 Cd responsive genes in other stress conditions (Zn, Ni, heat shock, M-NM-3-rays), and showed that the Cd transcriptional pattern is comparable to other metal stress transcriptional responses (Cd, Zn, Ni) but not to a general stress response. Kinetics of gene expression changes induced by Cd were performed at two different concentrations (0.1mM and 1mM) and at 3 time points (30, 120 and 270 min). A 0.1mM Cd concentration did not affect the growth rate, whereas 1mM Cd induced a transitory growth arrest for 270min. Late exponentially growing cells (7x107 cells/mL) were exposed to Cd and were collected after 30min, 120 min and after 270 min. For each time point, four slides containing the 2157 oligonucleotide gene probes printed in duplicate were hybridized. The experiment was repeated twice leading to eight data sets per time point (four per biological replicate). Microarray analyses monitored 161 transcriptional changes (M-bM-^NM-^_Fold Change (FC)M-bM-^NM-^\M-bM-^IM-%2 and p-Value M-bM-^IM-$ 0.01) in response to Cd exposure corresponding to 114 unique genes i.e. 5,3% of T. gammatolerans gene content, most of them being upregulated. While about 25% of the upregulated genes exhibited a FC>3 with a maximum of almost 10 for one encoding a conserved hypothetical protein (tg0885, 1mM Cd at 120min), the large majority of the up- and down-regulated genes exhibited a 2 to 3-fold transcriptional change as already described in many archaeal transcriptomic studies.
2012-07-31 | E-GEOD-13546 | biostudies-arrayexpress