Yu Ri An

Lipid metabolic effect of Korean red ginseng extract in mice fed on a high-fat diet

BACKGROUND Ginseng saponin and ginsenosides exert anti-obesity effects via the modulation of physiological lipid metabolism in vivo or intracellular signalling in cell culture systems. However, the complicated relationship between the anti-obesity effects of ginseng and gene expression has yet to be defined under in vivo conditions. Therefore, we evaluated the relationship between the anti-obesity effects of Korean red ginseng extract (KRGE) and hepatic gene expression profiles in mice fed long-term on a high-fat diet (HFD) in this study. RESULTS KRGE reduces the levels of cholesterol, low-density lipoprotein-cholesterol (LDL-C), serum triglycerides, and atherogenic indices. Levels of leptin, adiponectin and insulin, which regulate glucose and lipid metabolism, were impaired profoundly by HFD. However, KRGE treatment brought these levels back to normal. KRGE was found to down-regulate genes associated with lipid metabolism or cholesterol metabolism (Lipa, Cyp7a1, Il1rn, Acot2, Mogat1, Osbpl3, Asah3l, Insig1, Anxa2, Vldlr, Hmgcs1, Sytl4, Plscr4, Pla2g4e, Slc27a3, Enpp6), all of which were up-regulated by HFD. CONCLUSION KRGE regulated the expression of genes associated with abnormal physiology via HFD. Leptin, insulin, and adiponectin, which carry out critical functions in energy and lipid metabolism, were shown to be modulated by KRGE. These results show that KRGE is effective in preventing obesity.

Impact of miRNA deregulation on mRNA expression profiles in response to environmental toxicant, nonylphenol

MicroRNA (miRNA) are approximately 22nt RNA molecules with the ability to regulate gene expression by interacting with its target mRNA. Recent studies demonstrated that miRNA are responsible for determining cell fate and also plays an important role in cellular response to xenobiotics stress and other toxicological phenomenon. Also a number of reports have strengthened the correlation between altered miRNA expression and various cancers. In this study miRNA and mRNA expression profiling was carried out in in-vitro differentiating MCF-7 and HepG2 cell line to understand the effect of nonylphenol (NP), an industrially synthesized environmental toxicant. Analyzing the mRNA-miRNA interaction, we observed correlation between deregulated miRNAs and its predictive differentially expressed target mRNA. We also observed differential expression of two widely studied miRNAs, miR-21 and miR-34 in these cell lines. CTCF is found to be the predictive target of expressed miR-21 in MCF-7. In HepG2 cell line expressed MDM2 is found to be a predictive target of miR-34b. These results support the possible role of miRNA interaction in the expression of its target genes and also ability of environmental toxicant to deregulate miRNA expression.

Toxicology study with microRNA

AbstractmicroRNAs have a principal role in many biological processes, such as gene expression, control and development, as well as cellular processes. In recent years, microRNAs have attracted great interest in the field of toxicology. When organisms are exposed to toxic compounds, microRNAs expression is altered, which affects mRNA transcription and protein translation and causes adverse biological effects. Here, we introduce microRNAs as research tools, the specific expression profile of microRNAs following exposure to different toxicants or diseases that were found to be sensitive biomarkers. Finally, we address several issues related to microRNAs in toxicological studies.

Gene expression profiling of HepG2 cells treated with endocrine disrupting chemicals using the HazChem human array V3

The endocrine system is a system of glands that secrete hormones to regulate the body. This system is disrupted by endocrine disrupting chemicals (EDCs), which are similar to sex hormones. These chemicals function as androgen antagonists or estrogen agonists. To determine the effect of EDCs on the gene expression profile in human cells, we treated HepG2 cells with 3 chemicals (bisphenol A, 17β-estradiol, vinclozolin), and analyzed common gene expression using a custom-made HazChem human array V3. The Haz-Chem human array V3 included a total of 1136 genes, all of which were differentially expressed by exposure to VOCs, PAHs, POPs, and LTCs. Of these genes, 24 genes were commonly expressed after exposure to all 3 chemicals, based on the SAM (Significant Analysis of Microarray) method (q-value < 0.5%). These genes were analyzed further and found to be involved in coagulation, hemostasis, wound healing, angiogenesis, homeostasis, cell redox homeostasis, and cell proliferation based on GO function and pathway networks.

Identification of genetic/epigenetic biomarkers for supporting decision of VOCs exposure

Ethylbenzene, toluene and xylene are widely used volatile organic compounds (VOCs). VOCs are dangerous to human health or cause harm to the environment. The assessment of VOC exposure maybe carried out through a number of techniques. One of them, the epigenetic biomarker applies a new technology. Environmental epigenetics focuses on how cells or organisms respond to environmental factors to create altered phenotypes or diseases. In this study, our intention was to conduct an investigation of epigenetic biomarkers in VOCs. For the experiment, we used the DNAs and RNAs from VOC exposed human blood and VOCs treated cell lines. Then, we compared the data using microarray fold change, real-time PCR and methylation specific PCR. As a result, we identified five microRNAs (miR-520g, miR-424, miR-210, miR-21, and miR-142-3p), three methylation regions (SERPINB5, ZC3H3, and PCSK6) and four transcripts (CRCT1, RUNX3, PCDH11X, and PCSK6), which could be used as biomarkers for VOCs, becommings the foundation for a system which can predict VOC exposure.

Analysis of toxicity of tetrabutyltin: comparing with EDC chemicals

Exposure to environmental chemicals has been implicated in a number of adverse health effects, including immunotoxic, neurotoxic, reproductive toxic effects, and, above all, cancers. In the present study, we investigated toxicity of three environmental chemicals-bisphenol A (BPA), nonylphenol (NP), and tetrabutyltin (TTBT) in a human breast cancer cell line by HazChem Human array. We then found toxicity markers of TTBT through comparison with BPA and NP. Fifty three genes were differentially expressed and seventeen genes showed similar expression patterns. Ontology analysis showed differential expression of genes related to aging and apoptosis and genes having similarities associated with pregnancy and insemination. In this paper, we revealed potential TTBT toxic markers and endotoxicity of TTBT. This study could be a foundation for additional studies of TTBT toxicity.

Genomic comparison of insecticides and herbicide in human hepatoma (HepG2) cell line

Pesticide is a chemical substance, biological agent, antimicrobial, disinfectant or device used against any pest, and it can be grouped in several different ways. Atrazine is one of the most commonly used herbicides found in the rural environments, permethrin and prallethrin are pyrethroid insecticides. In this study, we compared the characters of herbicide and insecticide by cytotoxicity and microarray experiments. In the cytotoxicity tests, we couldn’t find specific chemical features. However, in the gene expression analysis, we found that insecticides affects to RNA processing and RNA metabolism, and especially, in the energy metabolism, such as generation of precursor metabolites and energy, and energy derivation by oxidation of organic compounds, herbicides and insecticides are differently working. This study provides characteristics of two pesticides by checking the transcriptional change.

Functional analysis of endocrine disruptor pesticides affected transcriptome and microRNA regulation in human hepatoma cell line

Endocrine disrupting chemicals (EDCs) alter the normal endocrine system of wildlife and humans. Among pesticides, a large number of chemicals have been identified as endocrine disruptors. Pesticides are designed to be toxic to pests and vectors of disease; however, human beings can easily be exposed to these chemicals because they are present in the environment at very low levels. In the present study, we examined the adverse effects of endocrine disrupting chemicals by screening transcripts and microRNAs. microRNAs are known as regulators of many protein coding genes. Therefore, the microRNAs regulating mRNAs were analyzed, including functional analysis. In addition, we tried to compare two types of chemicals, endocrine disruptor pesticides and EDCs. Endocrine disruptor pesticides were found to affect the reproductive or development systems by altering the Wnt signaling pathway, similar to EDCs. On the other hand, the genes involved in axon guidance and ubiquitin-mediated proteolysis were differentially regulated by treatment with endocrine disruptor pesticides compared with EDCs.

Analysis of microRNA and gene expression profiling in triazole fungicide-treated HepG2 cell line.

MicroRNA (miRNA) plays an important role in various diseases and in cellular and molecular responses to toxicants. In the present study, we investigated differential expression of miRNAs in response to three triazole fungicides (myclobutanil, propiconazole, and triadimefon). The human hepatoma cell line (HepG2) was treated with the above triazoles for 3 h or 48 h. miRNA-based microarray experiments were carried out using the Agilent human miRNA v13 array. At early exposure (3h), six miRNAs were differentially expressed and at late exposure (48 h), three miRNAs were significantly expressed. Overall, this study provides an array of potential biomarkers for the above triazole fungicides. Furthermore, these miRNAs induced by triazoles could be the foundation for the development of a miRNA-based toxic biomarker library that can predict environmental toxicity.

Prediction of VOCs based on functional analysis by decision supporting system

In the industrial age, people are exposed to many hazardous substances in many ways. Generally, exposure is of low doses, but chronic symptoms are associated with many industrial pollutants, and therefore, early prediction of exposure is important. In this study, we intended to determine the reliability of the predictive modeling and biomarkers of a previous study, and to determine the related pathway of that biomarkers. We analyzed the key pathways and biological processes associated with volatile organic compounds (VOCs) from previous data — VOCs biomarker CRCT1, RUNX3, PCDH11X and PCSK6. In the analysis, inflammation and neoplasm were remarkably frequently occurring disease within the VOCs exposed body, and especially, exposure to toluene, presents a great likelihood of nerve disease or nervous system disease. Those diseases were related with the several biological processes, they are cell proliferation, apoptosis, inflammatory response, and nervous system development. This study shows probability that application of decision supporting systems, moreover it is helpful to decide whether VOCs exposure has occurred or not, and to predict negative effects.