Project description:From the result of comparative the gene expression analyses of human hepatoma cell line, HepG2 following exposures of three heavy metals; arsenic, cadmium and nickel and three carcinogens; N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA) and tetrachloroethylene (TCE), 31-55% of the genes altered by As, Cd and Ni exposure were overlapped with those by three model carcinogen exposures in our experiments. In particular, three heavy metals shared certain characteristics with TPA and TCE in remarkable up-regulations of the genes associated with progression of cell cycle, which might play a central role in heavy metal carcinogenesis. In addition, this characteristic of gene expressions alteration was counteracted by intracellular accumulation of vitamine C in As-exposed cells but not in Cd- and Ni-exposed cells. These results suggest that the cell proliferative responses are caused by reactive oxygen species mainly in As exposure, while other mechanisms would be involved in these responses in Cd and Ni exposures. Experiment Overall Design: In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2 following exposures of three heavy metals; arsenic, cadmium and nickel and three carcinogens; N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA) and tetrachloroethylene (TCE) using DNA microarray with 8795 human genes. Furthermore, we also performed the DNA microarray analyses for the heavy metal exposed-cells that were loaded with vitamine C beforehand to examine the effects of antioxidant molecule to heavy metal exposures.
Project description:From the result of comparative the gene expression analyses of human hepatoma cell line, HepG2 following exposures of three heavy metals; arsenic, cadmium and nickel and three carcinogens; N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA) and tetrachloroethylene (TCE), 31-55% of the genes altered by As, Cd and Ni exposure were overlapped with those by three model carcinogen exposures in our experiments. In particular, three heavy metals shared certain characteristics with TPA and TCE in remarkable up-regulations of the genes associated with progression of cell cycle, which might play a central role in heavy metal carcinogenesis. In addition, this characteristic of gene expressions alteration was counteracted by intracellular accumulation of vitamine C in As-exposed cells but not in Cd- and Ni-exposed cells. These results suggest that the cell proliferative responses are caused by reactive oxygen species mainly in As exposure, while other mechanisms would be involved in these responses in Cd and Ni exposures. Keywords: other
Project description:From the results of gene expression analyses of HepG2 under the exposure of 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ), N-nitrosodimethylamine (DMN), phenol and six heavy metals We showed that biological action of six heavy metals were clearly related to that of DMNQ and distinguishable from the other chemicals. These results suggest that oxidative stress is major apparent biological action of high dose heavy metals, supporting the previous reports. Experiment Overall Design: Using Affymetrix HG-Focus arrays, we compared the gene expression patterns of Hep G2 cells induced by six heavy metals (As, Cd, Ni, Sb, Hg or Cr) with that of DMNQ, DMN or phenol, and evaluated the toxicities of these heavy metals.
Project description:Background: The high number of heavy metal resistance genes in the soil bacterium Cupriavidus metallidurans CH34 makes it an interesting model organism to study microbial responses to heavy metals. Results: In this study the transcriptional response of this bacterium was measured after challenging it to a wide range of sub-lethal concentrations of various essential or toxic metals. Considering the global transcriptional responses for each challenge as well as by identifying the overlap in upregulated genes between different metal responses, the sixteen metals could be clustered in three different groups. Additionally, next to the assessment of the transcriptional response of already known metal resistance genes, new metal response gene clusters were identified. The majority of the metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex cross-talk at transcriptional level between the different metal responses. The highly redundant nature of these metal resistant regions – illustrated by the large number of paralogous genes – combined with the phylogenetic distribution of these metal response regions within evolutionary related and other metal resistant bacteria, provides important insights on the recent evolution of this naturally soil dwelling bacterium towards a highly metal-resistant strain found in harsh and anthropogenic environments. Conclusions: The metal-resistant soil bacterium Cupriavidus metallidurans CH34 displays myriads of gene expression patterns when exposed to a wide range of heavy metals at non-lethal concentrations. The interplay between the different gene expression clusters points towards a complex cross-regulated regulatory network governing heavy metal resistance in C. metallidurans CH34. Keywords: Cupriavidus metallidurans CH34, transcriptional regulation, heavy metal resistance Two-condition experiments. Comparing samples after induction with heavy metals versus non-induced samples. Biological duplicate or triplicate. Each array contains 3 or 4 technical replicates.
Project description:Background: The high number of heavy metal resistance genes in the soil bacterium Cupriavidus metallidurans CH34 makes it an interesting model organism to study microbial responses to heavy metals. Results: In this study the transcriptional response of this bacterium was measured after challenging it to a wide range of sub-lethal concentrations of various essential or toxic metals. Considering the global transcriptional responses for each challenge as well as by identifying the overlap in upregulated genes between different metal responses, the sixteen metals could be clustered in three different groups. Additionally, next to the assessment of the transcriptional response of already known metal resistance genes, new metal response gene clusters were identified. The majority of the metal response loci showed similar expression profiles when cells were exposed to different metals, suggesting complex cross-talk at transcriptional level between the different metal responses. The highly redundant nature of these metal resistant regions – illustrated by the large number of paralogous genes – combined with the phylogenetic distribution of these metal response regions within evolutionary related and other metal resistant bacteria, provides important insights on the recent evolution of this naturally soil dwelling bacterium towards a highly metal-resistant strain found in harsh and anthropogenic environments. Conclusions: The metal-resistant soil bacterium Cupriavidus metallidurans CH34 displays myriads of gene expression patterns when exposed to a wide range of heavy metals at non-lethal concentrations. The interplay between the different gene expression clusters points towards a complex cross-regulated regulatory network governing heavy metal resistance in C. metallidurans CH34. Keywords: Cupriavidus metallidurans CH34, transcriptional regulation, heavy metal resistance
Project description:Transcription profile of HepG2 cells treated with hepatocyte growth factor and control cells Two condition experiment, Hep G2 vs. Hep G2-HGF. Biological replicates: 1 control and 1 HGF-treated (no replication)
Project description:Heavy metals residue in the natural ecosystem had become one global environmental problem that was eager to solve. Due to the non-biodegradability, organism could deposit excessive heavy metals elements into tissues. Existing literature proposed that prolonged heavy metals enrichment had comprehensive toxicity to multi-organs of vertebrates. However, little research focus on the molecular mechanism for the hepatotoxicity of heavy metal enrichment to Chiroptera. In the present study, ten Hipposideros armiger individuals from Yingde City (YD, relatively pollution-free) and Chunwan City (CW, excessive heavy metals emission) were dissected while environment samples were also obtained. To corroborate the toxicity mechanism of heavy metals to bats liver, multi-omics, pathology and molecular biology methods were performed. Our results showed that more Cd and Pb elements were significantly enriched in bats liver and food sources in the CW group. In addition, prolonged heavy metals accumulation disturbed the hepatic transcription profiling associated with solute carriers family, ribosome pathway, ATP usage and heat shock proteins. Excessive heavy metals enrichment also altered the relative abundance of typical gut microbe taxa to inhibit the tight-junction protein expression. We also found that the levels of superoxide dismutase, glutathione peroxidase and glutathione were decreased while ROS density and malondialdehyde content were elevated after excessive heavy metals enrichment. Besides, hepatic fat accumulation and inflammation injury were also observed under the excessive heavy metals enrichment while the metabolism biomarkers contents were decreased. Therefore, prolonged heavy metals enrichment would induce a series of hepatotoxicity by disturbing the microbes-gut-liver axis and hepatic transcription modes, which could decrease the overall metabolism level in bats. Our study provided protection strategy for biodiversity conservation and raised public attention to environment pollution.
Project description:From the results of gene expression analyses of HepG2 under the exposure of 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ), N-nitrosodimethylamine (DMN), phenol and six heavy metals We showed that biological action of six heavy metals were clearly related to that of DMNQ and distinguishable from the other chemicals. These results suggest that oxidative stress is major apparent biological action of high dose heavy metals, supporting the previous reports. Keywords: other