Jae-Chun Ryu

Korea University of Science and Technology, Sŏul, Seoul, South Korea

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Publications (95)152.83 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM2.5), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM2.5[water (W-PM2.5) and organic (O-PM2.5) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM2.5 and O-PM2.5, respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM2.5 and O-PM2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM2.5-induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
    No preview · Article · Jan 2016 · Environmental Toxicology
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    ABSTRACT: Many epidemiological and in vitro studies have shown that particulate matter 2.5 (PM2.5) is associated with adverse health effects in humans, especially respiratory morbidity and mortality1–3. While the mechanisms for these effects have been vigorously investigated for many years, they still remain uncertain. In previous studies, we collected PM2.5 samples in Seoul, Korea, where pollution results from a high level of automobile traffic, and analyzed the chemical composition of PM2.5. In the present study, we used gene expression profiling and gene ontology (GO) analysis to identify the gene expression changes in A549 human alveolar epithelial cells induced by exposure to water and organic extracts of PM2.5 (W-PM2.5 and O-PM2.5) in order to evaluate the adverse health effects of PM2.5. Transcriptomic profiling indicates that the O-PM2.5 exposure group was more sensitive in gene alterations than the W-PM2.5 exposure group. Through analysis of gene expression profiles, we identified 149 W-PM2.5-specific genes and 516 O-PM2.5-specific genes, as well as 173 commonly expressed genes in both the W-PM2.5 and O-PM2.5 exposure groups. After gene ontology (GO) analysis on the O-PM2.5-specific genes, we determined several key pathways that are known to be related to increasing pulmonary toxicity, such as immune response, regulation of inflammatory response, metabolism of xenobiotics by cytochrome P450, and retinol metabolism. However, we did not find the pulmonary toxicity-related pathways through GO analysis on the W-PM2.5-specific genes. In addition, 173 commonly expressed genes are involved in tyrosine catabolic process, retinol metabolism pathway, and steroid hormone biosynthesis — all of which are known to induce adverse health effects. In conclusion, this report describes changes in gene expression profiles in an in vitro respiratory system in response to exposure to PM2.5 water and organic extracts and relates these gene expression changes to pulmonary toxicity related pathways. This experiment adds to the understanding of how cells respond to PM2.5 exposure through transcriptional regulation. © 2014, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht.
    No preview · Article · Dec 2015 · Molecular and Cellular Toxicology
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    ABSTRACT: In previous studies, we have investigated the relationships between environmental chemicals and health risk based on omics analysis and identified significant biomarkers. Our current findings indicate that hexanal may be an important toxicant of the pulmonary system in epigenetic insights. MicroRNA (miRNA) is an important indicator of biomedical risk assessment and target identification. Hexanal is highly detectable in the exhaled breath of patients with chronic obstructive pulmonary disease (COPD) and chronic inflammatory lung disease. In this study, we aimed to identify hexanal-characterized miRNA-mRNA correlations involved in lung toxicity. Microarray analysis identified 56 miRNAs that commonly changed their expression more than 1.3-fold in three doses (600, 1000, and 1500 ppm) within hexanal-exposed Fischer 344 rats by inhalation, and 226 genes were predicted to be target genes of miRNAs through TargetScan analysis. By integrating analyses of miRNA and mRNA expression profiles, we identified one anti-correlated target gene (Chga; chromogranin A; parathyroid secretory protein 1). Comparative toxicogenomics database (CTD) analysis of this gene showed that Chga is involved with several disease categories such as cancer, respiratory tract disease, nervous system disease, and cardiovascular disease. Further research is necessary to elucidate the mechanisms of hexanal-responsive toxicologic pathways at the molecular level. This study concludes that our integrated approach to miRNA and mRNA enables us to identify molecular events in disease development induced by hexanal in an in vivo rat model. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.
    No preview · Article · Sep 2015 · Environmental Toxicology
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    ABSTRACT: The removal of heavy metals from industrial wastewater is important, owing to its eco-toxicity in aqueous environment. In this study, the mechanism and efficiency of the removal of toxic heavy metals by an eco-friendly adsorbent was investigated. Various types of adsorbents made from jujube were synthesized by varying the drying temperature of gel-type beads and elution method for jujube constituents. The maximum adsorption capacity for lead and copper ions was determined using the Langmuir isotherm model, with DJB-A-S-F (freeze-dried jujube bead made from a solution of squeezed autoclaved jujube) having the highest values at 60.44 mg/g (lead) and 20.33 mg/g (copper). In addition, the characteristics of the various adsorbents were determined by the Brunauer–Emmett–Teller (BET) method, scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Gas chromatography–mass spectrometry (GC–MS) was used to identify the constituents of DJB-A-S-F before and after adsorption of heavy metals (Pb- and Cu-DJB-A-S-F). Furthermore, in vitro cytotoxicity assay was performed to investigate whether the binding of heavy metals to DJB-A-S-F increases cellular toxicity. As a result, no differences in cell viability between DJB-A-S-F and the ones coupled to heavy metals were observed, indicating that the developed adsorbents are non-cytotoxic with good compatibility. Thus, DJB-A-S-F is a promising adsorbent for the removal of toxic heavy metal cations from wastewater.
    No preview · Article · Aug 2015 · Reactive and Functional Polymers
  • Mi-Kyung Song · Jae-Chun Ryu
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    ABSTRACT: To date, there is still shortage of highly sensitive and specific minimally invasive biomarkers for assessment of environmental toxicants exposure. Because of the significance of microRNA (miRNA) in various diseases, circulating miRNAs in blood may be unique biomarkers for minimally invasive prediction of toxicants exposure. We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis. We identified 467 miRNAs for TOL, 211 miRNAs for XYL, and 695 miRNAs for XYL as characteristic discernible exposure indicator, which could discerned each VOC from the control group with higher accuracy, sensitivity, and specificity than urinary biomarkers. Current observations from this study point out that the altered levels of circulating miRNAs can be a reliable novel, minimally invasive biological indicator of occupational exposure to VOCs. Copyright © 2015 Elsevier GmbH. All rights reserved.
    No preview · Article · Jun 2015 · International journal of hygiene and environmental health
  • Mi-Kyung Song · Hyo-Sun Lee · Jae-Chun Ryu
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    ABSTRACT: We have shown that aldehydes impact the bronchial airway gene expression associated with inflammatory responses. In this study, we sought to determine whether microRNA (miRNA) plays a role in regulating the airway gene expression response to aldehyde exposure. We analyzed the whole genome miRNA and mRNA expression profiles of human alveolar epithelial cells exposed to 3 aldehydes (propanal, butanal, and pentanal) to identify aldehyde-sensitive miRNAs and to characterize the relationships between miRNAs and the expression of candidate cytokine-related genes, which are activated in response to inflammatory signals. Microarray analysis identified 15 miRNAs for propanal, 25 miRNAs for butanal, and 10 miRNAs for pentanal, which were differentially expressed in A549 human alveolar epithelial cells compared with vehicle control samples. Integrated analyses of miRNA and mRNA expression profiles identified significant miRNA-mRNA correlations. Gene ontology (GO) analysis of putative target genes (443 genes for propanal, 2166 genes for butanal, and 364 genes for pentanal) showed that the biological category "Cytokine-cytokine receptor interaction" was prominently annotated. Moreover, we detected increased levels of interleukin (IL)-6 and IL-8 released in the 3 aldehyde exposure groups. Through an integrated analysis of the miRNA and mRNA expression profiles of aldehydes, we provide evidence that aldehyde can affect cytokine-induced toxicity signaling. Therefore, this study demonstrates the added value of an integrated miRNA-mRNA approach for identifying molecular events altered by environmental pollutants in an in vitro human model. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Jun 2015 · Toxicology
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    ABSTRACT: Although hexanal is considered to be a major air pollutant the correlation between hexanal and health risk is largely unknown. Identifying aldehyde toxicity in eukaryotic cells will be useful for preventing and treating environmental diseases and disorders. However, it is important to note that previous microRNA (miRNA) studies of hexanal have not yet identified the functional relationship between miRNA and mRNA. The aim of this study is to investigate the modulation of the integrated miRNA-mRNA relationship following exposure to hexanal. A549 human alveolar epithelial cells were treated to a 20% inhibitory concentration (IC20) of hexanal for 48 h. The microarray analysis results showed that 6 miRNA were altered in the hexanal-exposed A549 cells. Integrated analysis of miRNA and mRNA expression profiles identified 445 miRNA-mRNA correlations. KEGG analysis of 445 putative target genes of hexanal-induced miRNAs indicated that 8 genes (ATP2B3, ATP2B4, CACNA1G, EDNRA, GRM5, ITPR2, ITPKB, PTGER3) are involved in the calcium signaling pathway, which plays an important role in Alzheimer’s and several inherited immunodeficiency diseases. Therefore, this study suggests the value of miRNA-mRNA networks in order to identify molecular regulation in response to hexanal exposure in an in vitro model. Furthermore, this approach provides insight into the potential biological process of toxicity and a better understanding of the toxicological mechanism of toxicants. © 2015, Korean Society of Environmental Risk Assessment and Health Science and Springer Science+Business Media Dordrecht.
    No preview · Article · Jun 2015 · Toxicology and Environmental Health Sciences
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    ABSTRACT: A pure clay ball and surface-modified clay ball were investigated to remove phosphate from synthetic wastewater; phosphate causes eutrophication in hydro-ecological systems. Adsorption tests of phosphate from aqueous solutions onto two types of adsorbents were conducted. The maximum phosphate adsorption capacities of the pure and surface-modified clay ball were found to be 0.084 and 8.869 mg/g, respectively. In a fixed-bed column packed with surface-modified clay balls, the first breakthrough of phosphate appeared after approximately 4000 min. In addition, the phosphate adsorbed on the surface-modified clay ball was effectively desorbed using a 1 M zirconium sulfate solution, and the adsorbent was regenerated for four adsorption and three desorption cycles by maintaining the adsorption capacity at the value before regeneration. X-ray diffraction (XRD), scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), and Brunauer-Emmett-Teller (BET) analysis method were performed to reveal the characteristics of the surface-modified clay ball. Cytotoxicity experiment was conducted on the developed adsorbents, and as a result, these showed low cytotoxic effect on the human cells. These results indicated that the surface-modified clay ball, due to the low cost, high adsorption capacity, and non-toxicity, has the potential to be utilized in the cost-effective removal of phosphate from aqueous solutions.
    No preview · Article · Apr 2015 · Water Air and Soil Pollution
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    ABSTRACT: Pure and surface-modified basanites (SMBs) were investigated for treatment of nutrients such as ammonium nitrogen and phosphate in aqueous solution. Basanite is a volcanic rock with a large specific surface area due to its vesicular structure. Moreover, basanite contains silica and calcium, promoting surface fixation of hydroxyl groups. The equilibrium adsorption of ammonium nitrogen and phosphate in aqueous solutions by four types of basanite adsorbents was evaluated. The adsorption isotherms were well described by a Langmuir adsorption model. Among the adsorbents, the SMB prepared by reaction with 20 % sodium hydroxide had the highest adsorption capacities for ammonium nitrogen (5.38 mg/g) and phosphate (19.74 mg/g). In addition, cytotoxicity of the pure basanite and SMBs was also evaluated. None of the basanite adsorbents showed cytotoxic effects to human cells at concentration in effluents. Thus, the SMBs were found to be promising materials for removal of ammonium nitrogen and phosphate from sewage.
    No preview · Article · Aug 2014 · Water Air and Soil Pollution
  • Mi-Kyung Song · Han-Seam Choi · Hyo-Sun Lee · Jae-Chun Ryu
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    ABSTRACT: In current study, we aimed to investigate the transcriptomic responses and identify specific molecular signatures of Low-molecular-weight saturated aliphatic aldehydes (LSAAs). To evaluate the change in gene expression levels, A549 human alveolar epithelial cells were exposed to six LSAAs (propanal, butanal, pentanal, hexanal, heptanal, and octanal) for 48 h. Clustering analysis of gene expression data show that the low carbon number group (LCG; propanal, butanal, and pentanal) was distinguished from the high carbon number group (HCG; hexanal, heptanal, and octanal). Also, transcriptomic profiling indicates that LCG exposure group was more sensitive in gene alterations than HCG group. Supervised analysis revealed 703 LCG specific genes and 55 HCG specific genes. After Gene Ontology (GO) analysis on LCG specific genes, we determined several key pathways which are known as related to increase pulmonary toxicity such as cytokine-cytokine receptor interaction and chemokine signaling pathway. But we did not find pulmonary toxicity-related pathways through GO analysis on HCG specific genes. Genes that are expressed in only low carbon LSAAs exposure group were regarded as biomarker of aldehydes-induced pulmonary toxicity. In conclusion, this study describes changes in gene expression profiles in in vitro respiratory system in response to exposure to 6 LSAAs with different carbon number and relates these gene alterations to pulmonary toxicity related pathways. Moreover, novel carbon number-specific genes and pathways can be more widely implemented in combination with traditional technique for assessment and prediction of exposure to environmental toxicants.
    No preview · Article · Jul 2014 · Chemical Research in Toxicology
  • Yoon Cho · Mi-Kyung Song · Han-Seam Choi · Jae-Chun Ryu
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    ABSTRACT: The problems of analyzing dose effects on gene expression are gaining attention in toxicological research. Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and elucidating their modes of toxic action. In the present study, we focused on determining the dose-dependent alterations of gene expression profiles with hexanal exposure and we identified the possible biomarkers of hexanal in A549 human alveolar cells. A549 cells were exposed to a 5% inhibitory concentration (IC5) and a 20% inhibitory concentration (IC20) of hexanal for 48 h. Through microarray analysis using an oligonucleotide chip, we identified that the gene expression patterns were differentially shown in the control group and the hexanalexposed groups. The hexanal-exposed groups are more sensitive to gene alteration than the control group, and gene expressions are more significantly altered in the IC20 exposure group than in the IC5 exposure group. With clustering analysis of gene expression profiles, we identified 2,929 IC5− and 3,678 IC20-specific genes, and 302 dose-dependently expressed genes. Gene ontology (GO) analysis with 246 annotated genes of the 302 dosedependent expressed genes showed correlation with the key biological processes involved in neurological system processes, immune system development, cell activation, and cell-cell signaling. In conclusion, current study describes alterations in gene expression profiles in response to exposure to different doses of hexanal and related toxic pathways induced by significantly expressed genes. Moreover, novel genes and pathways that could potentially play a role in the prevention of respiratory disease due to aldehydes are identified.
    No preview · Article · Jun 2014 · BioChip journal
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    ABSTRACT: The composites of mesostructured iron oxyhydroxide and/or commercial synthetic zeolite were investigated for use in the removal of toxic heavy metals, such as cadmium, copper, lead and arsenic, from aqueous solution. Four types of adsorbents, dried alginate beads (DABs), synthetic-zeolite impregnated beads (SZIBs), meso-iron-oxyhydroxide impregnated beads (MIOIBs) and synthetic-zeolite/meso-iron-oxyhydroxide composite beads (SZMIOIBs), were prepared for heavy metal adsorption tests. Laboratory experiments were conducted to investigate the removal efficiencies of cations and anions of heavy metals and the possibility of regenerating the adsorbents. Among these adsorbents, the MIOIBs can simultaneously remove cations and anions of heavy metals; they have high adsorption capacities for lead (60.1mgg(-1)) and arsenic (71.9mgg(-1)) compared with other adsorbents, such as DABs (158.1 and 0.0mgg(-1)), SZIB (42.9 and 0.0mgg(-1)) and SZMIOIB (54.0 and 5.9mgg(-1)) for lead and arsenic, respectively. Additionally, the removal efficiency was consistent at approximately 90%, notwithstanding repetitive regeneration. The characteristics of meso-iron-oxyhydroxide powder were confirmed by X-ray diffraction, Brunauer-Emmett-Teller and transmission electron microscopy. We also performed a comparative toxicity study that indicated that much lower concentrations of the powdered form of mesostructured iron oxyhydroxide had stronger cytotoxicity than the granular form. These results suggest that the granular form of meso iron oxyhydroxide is a more useful and safer adsorbent for heavy metal treatment than the powdered form. This research provides promising results for the application of MIOIBs as an adsorbent for various heavy metals from wastewater and sewage.
    No preview · Article · Jan 2014 · Journal of hazardous materials
  • Han-Seam Choi · Mi-Kyung Song · Jae-Chun Ryu
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    ABSTRACT: We have shown that aldehydes impact gene expression profiles of bronchial airway associated with pulmonary toxicity. In this study, we aimed to determine whether microRNA (miRNA) plays a role in regulating the airway gene expression response to aldehyde exposure. We analyzed whole genome miRNA and mRNA expression profiles upon nonanal exposure of human alveolar epithelial cells to identify nonanalsensitive miRNAs and to characterize the relationships between miRNAs and the expression of the candidate target genes involved in aldehyde-induced toxicity. Microarray analysis identified six miRNAs that were differentially expressed in nonanal-exposed A549 human alveolar cells. Integrated anti-correlation analyses of miRNA and mRNA expression profiles identified 157 putative target genes. GO analysis of 157 putative target genes demonstrated that the biological category “apoptosis-related pathway” was prominently annotated. Moreover, we detected an increased number of apoptotic cells in the nonanal-exposed group. By integrating the transcriptome and microRNAome, we provide evidence that nonanal can affect apoptosisinduced toxicity signaling. Therefore, this study proves the benefit of an integrated miRNA-mRNA approach for identifying toxicity mechanisms induced by environmental toxicants using an in vitro human model.
    No preview · Article · Dec 2013 · Molecular and Cellular Toxicology
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    ABSTRACT: Low-molecular weight saturated aliphatic aldehydes (LSAAs), which include propanal, butanal, pentanal, hexanal, octanal, nonanal and heptanal, are volatile organic compounds (VOCs). They are ubiquitous in the environment of our daily life. Although LSAAs are harmful, with mutagenic and carcinogenic effects, the mechanisms underlying the toxicity of volatile aldehydes are still unclear. Therefore, in this study, we performed genome-wide expression profile analysis of A549 human alveolar epithelial cells exposed to seven LSSAs. We selected genes whose expression was changed more than 1.5-fold in A549 cells exposed to LSAAs by analysis of gene expression profiles using human oligonucleotide chips. Through gene expression profiling, we showed that LSSAs are related to the key biological processes “defense response”, “inflammatory response” and “immune response” in gene ontology (GO) analysis. In addition, we identified two genes that were up-regulated (GREB1, BC009808) and four that were down-regulated (UCP1, TCP11, FNDC3A, LOC645206) by all the tested LSAAs. Our data suggest that LSAAs exert toxic effects on A549 cells by modulating mRNA expression. Moreover, we suggest that genes expressed in response to LSAAs represent a molecular signature that can be widely used, in combination with more traditional techniques, to assess and predict the toxicity caused by exposure to LSAAs.
    Preview · Article · Dec 2013 · Toxicology and Environmental Health Sciences
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    ABSTRACT: Previous environmental microRNA (miRNA) studies have investigated a limited number of candidate miRNAs and have not evaluated functional effects on gene expression. In this study, we aimed to identify octanal (OC)-sensitive miRNAs and to characterize the relationships between miRNAs and expression of candidate genes involved in OC-induced toxicity. Microarray analysis identified 15 miRNAs that were differentially expressed in OC-exposed A549 human alveolar cells. Integrated analyses of miRNA and mRNA expression profiles identified significant miRNA-mRNA anti-correlations. GO analysis of 101 putative target genes showed that the biological category 'MAPK signaling pathway' was prominently annotated. Moreover, we detected increased phosphorylation of p38 MAPK in the OC-exposed group. By integrating the transcriptome and microRNAome, we provide evidence that OC can affect MAPK-induced toxicity signaling. Therefore, this study demonstrates the added value of an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model.
    No preview · Article · Nov 2013
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    ABSTRACT: Gene expression data may be very promising for the classification of toxicant types, but the development and application of transcriptomic-based gene classifiers for environmental toxicological applications are lacking compared to the biomedical sciences. Also, simultaneous classification across a set of toxicant types has not been investigated extensively. In the present study, we determined the transcriptomic response to three types of ubiquitous toxicants exposure in two types of human cell lines (HepG2 and HL-60), which are useful in vitro human model for evaluation of toxic substances that may affect human hepatotoxicity (e.g., polycyclic aromatic hydrocarbon [PAH] and persistent organic pollutant [POP]) and human leukemic myelopoietic proliferation (e.g., volatile organic compound [VOC]). The findings demonstrate characteristic molecular signatures that facilitated discrimination and prediction of the toxicant type. To evaluate changes in gene expression levels after exposure to environmental toxicants, we utilized 18 chemical substances; nine PAH toxicants, six VOC toxicants, and three POP toxicants. Unsupervised gene expression analysis resulted in a characteristic molecular signature for each toxicant group, and combination analysis of two separate multi-classifications indicated 265 genes as surrogate markers for predicting each group of toxicants with 100 % accuracy. Our results suggest that these expression signatures can be used as predictable and discernible surrogate markers for detection and prediction of environmental toxicant exposure. Furthermore, this approach could easily be extended to screening for other types of environmental toxicants.
    No preview · Article · Nov 2013 · Environmental Science and Pollution Research
  • Youn-Jung Kim · Jina Lee · Mi-Kyung Song · Taejun Han · Jae-Chun Ryu
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    ABSTRACT: Valproic acid is commonly used to treat seizure disorders, bipolar disorder, migraine prophylaxis, and neuropathic pain. Despite its effectiveness and widespread use, valproic acid has been proven to exert considerable teratogenic potential, such as neural tube defects and malformations of the heart in both the humans and animals. However, the molecular mechanism of the teratogenic effects of valproic acid has not been fully elucidated. Because adverse effects in fetus by teratogens are obviously detectable only after birth and there are the limits of teratogenicity testing using rodents, such as thalidomide tragedy, new strategies for pre-determining teratogenic effects are required. Here, we try to elucidate the indirect teratogenicity of valproic acid in a human placenta-derived cell line (JEG-3) using a transcriptomic approach. In this study, using human whole genome oligonucleotide microarray, we identified 2,076 up- and 1,730 down-regulated genes which were changed more than 1.5-fold in JEG-3 cells exposed to valproic acid. Many of these genes have associations with lysosome, transport, tight junction, splicesome, cell cycle and mammalian target of rapamycin (mTOR)-signaling pathway. Among these, we focused on the adenosine monophosphate (AMP)-dependent kinase or AMP-activated kinase (AMPK)-mediated mTOR signaling pathway, and hypothesized that the negative control of mTOR signaling by AMPK might induce inhibition of the growth of JEG-3 cell exposed to valproic acid. First, flow cytometry analysis showed that valproic acid induced the inhibition of cell growth caused by G1 phase arrest. Second, the expression of genes related to mTOR signaling was changed. Using quantitative real-time RT-PCR data, it was confirmed that PTEN, PIK3CB, PIK3CD, PIK3R3, IRS2, and PRKAA2 (AMPKα2) were overexpressed, and that GβL and AKT1 were under-expressed in valproic acid treated JEG-3 cells compared to a control. We also confirmed the protein expression and the activation of AMPK and raptor after valproic acid exposure. Thus, this study suggests that valproic acid affects AMPK, and then AMPK may influence cell growth through mTOR signaling, and particularly, mTOR activity is suppressed by raptor activation. From this point of view, these genes may provide potential biomarkers that may contribute to decrease the number of candidate drugs showing teratogenicity in large-scale tests using placenta cells.
    No preview · Article · Sep 2013 · BioChip journal
  • Mi-Kyung Song · Yong-Keun Park · Jae-Chun Ryu
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    ABSTRACT: Growing evidence indicates that changes in microRNA (miRNA) expression in cancer induced by chemical carcinogens play an important role in cancer development and progression by regulating related genes. However, the mechanisms underlying miRNA involvement in hepatocarcinogenesis induced by polycyclic aromatic hydrocarbons (PAHs) remain unclear. Thus, identification of aberrant miRNA expression during PAH-induced cancer cell migration will lead to a better understanding of the substantial role of miRNAs in cancer progression. In the present study, miRNA expression profiling showed significant upregulation of miR-181a, -181b, and -181d in human hepatocellular carcinoma cells (HepG2 line) exposed to benzo[a]anthracene (BA) and benzo[k]fluoranthene (BF). MAPK phosphatase-5 (MKP-5), a validated miR-181 target that deactivates MAPKs, was markedly suppressed while phosphorylation of p38 MAPK was increased after BA and BF exposure. The migration of HepG2 cells, observed using the scratch wound-healing assay, also increased in a dose-dependent manner. Depletion of miR-181 family members by miRNA inhibitors enhanced the expression of MKP-5 and suppressed the phosphorylation of p38 MAPK. Furthermore, depletion of the miR-181 family inhibited cancer cell migration. Based on these results, we conclude that the miR-181 family plays a critical role in PAH-induced hepatocarcinogenesis by targeting MKP-5, resulting in regulation of p38 MAPK activation.
    No preview · Article · Aug 2013 · Toxicology and Applied Pharmacology
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    ABSTRACT: Particulate matter (PM) air pollution is a significant environmental issue. PM is divided into three main fractions based on its size: coarse (2.5–10 μm), fine (0.1–2.5 μm), and ultrafine fractions (<0.1 μm). Fine particles and ultrafine fractions which are designated as particulate matter 2.5 (PM2.5) is small enough to reach alveoli in the lungs. Although the correlation between the chemical composition of PM2.5 and its toxic mechanisms has not been elucidated, several studies of PM2.5 have found evidence that ambient air PM2.5 is associated with adverse health effects. In the present study, the chemical compositions of water- and organic-soluble extracts of PM2.5 from 50 sample filters collected in the winter in the middle part of Seoul were measured. The water-soluble extract was analyzed to determine its contents of inorganic ions and metals using ion chromatography, atomic absorption spectrometry, and inductively coupled plasma-atomic emission spectrometry. The main inorganic ions were Cl−, NO3−, SO42−, and NH4+, with a total quantity in the range of 20.02 to 40.22 μg/m3 in ambient air. In a sample of all five groups, Na, K, Ca, Mg, Cd, Cr, Cu, Fe, Mn, Ni, V, and Zn together accounted for 902.14 to 1631.25 ng/m3 in ambient air. The concentrations of thirteen polycyclic aromatic hydrocarbons (PAHs) in the organic-soluble extract were analyzed using gas chromatography/time of flight-mass spectrometry. The thirteen PAHs combined constituted 6.24–76.05 ng/m3 in ambient air. In this study, we report the chemical composition of PM2.5 during the winter season in Seoul and suggest using a high-volume air sampler to create water- and organic-soluble extracts from large amounts of PM2.5, which could be used to conduct in vitro and in vivo experiments, including studying genomic changes following PM exposure.
    Full-text · Article · Jun 2013 · Toxicology and Environmental Health Sciences
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    ABSTRACT: 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.
    No preview · Article · Mar 2013 · BioChip journal

Publication Stats

743 Citations
152.83 Total Impact Points

Institutions

  • 2014-2016
    • Korea University of Science and Technology
      Sŏul, Seoul, South Korea
  • 1996-2015
    • Korea Institute of Science and Technology
      • • Center for Water Resource Cycle Research
      • • Center for Integrated Risk Research
      • • Doping Control Center
      Sŏul, Seoul, South Korea
  • 2010-2012
    • Korea Institute of Toxicology
      Sŏul, Seoul, South Korea
  • 2008
    • Yeungnam University
      • College of Pharmacy
      Onyang, South Chungcheong, South Korea
  • 2003
    • Chungnam National University
      • College of Pharmacy
      Daiden, Daejeon, South Korea