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      Ecotoxicogenomic Approaches for Understanding Molecular Mechanisms of Environmental Chemical Toxicity Using Aquatic Invertebrate, Daphnia Model Organism

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          Abstract

          Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term “ecotoxicogenomics” has recently emerged to describe integration of omics studies ( i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development’s toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s) and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses) necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics.

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          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            Toxicity of nanosized and bulk ZnO, CuO and TiO2 to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus.

            As the production of nanoparticles of ZnO, TiO2 and CuO is increasing, their (eco)toxicity to bacteria Vibrio fischeri and crustaceans Daphnia magna and Thamnocephalus platyurus was studied with a special emphasis on product formulations (nano or bulk oxides) and solubilization of particles. Our innovative approach based on the combination of traditional ecotoxicology methods and metal-specific recombinant biosensors allowed to clearly differentiate the toxic effects of metal oxides per se and solubilized metal ions. Suspensions of nano and bulk TiO2 were not toxic even at 20 g l(-1). All Zn formulations were very toxic: L(E)C50 (mg l(-1)) for bulk ZnO, nanoZnO and ZnSO4.7H2O: 1.8, 1.9, 1.1 (V. fischeri); 8.8, 3.2, 6.1 (D. magna) and 0.24, 0.18, 0.98 (T. platyurus), respectively. The toxicity was due to solubilized Zn ions as proved with recombinant Zn-sensor bacteria. Differently from Zn compounds, Cu compounds had different toxicities: L(E)C50 (mg l(-1)) for bulk CuO, nano CuO and CuSO4: 3811, 79, 1.6 (V. fischeri), 165, 3.2, 0,17 (D. magna) and 95, 2.1, 0.11 (T. platyurus), respectively. Cu-sensor bacteria showed that toxicity to V. fischeri and T. platyurus was largely explained by soluble Cu ions. However, for Daphnia magna, nano and bulk CuO proved less bioavailable than for bacterial Cu-sensor. This is the first evaluation of ZnO, CuO and TiO2 toxicity to V. fischeri and T. platyurus. For nano ZnO and nano CuO this is also a first study for D. magna.
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              DNA methylation and histone modifications: teaming up to silence genes.

              DNA methylation, histone deacetylation, and methylation of histone H3 at lysine 9 are the three best-characterized covalent modifications associated with a repressed chromatin state. Recent advances highlight an essential, intricate web of interactions among these processes, generating a self-reinforcing, self-perpetuating cycle of epigenetic events that lead to long-term transcriptional repression. Histone deacetylation and methylation at lysine 9 of H3 might also contribute to the establishment of DNA methylation patterns, a long-standing mystery in epigenetics. What's more, recent clues suggest a potential link between CpG methylation and other histone modifications. A complex picture is emerging in which DNA methylation and histone modifications work hand-in-hand as parts of an epigenetic program that integrates gene-silencing networks within the cell.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                29 May 2015
                June 2015
                : 16
                : 6
                : 12261-12287
                Affiliations
                [1 ]Institute of Environmental Medicine for Green Chemistry, Dongguk University Biomedi Campus 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Korea; E-Mails: hd414@ 123456naver.com (H.J.K.); pkoedrith@ 123456gmail.com (P.K.)
                [2 ]Department of Life Science, Dongguk University Biomedi Campus 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-820, Korea
                [3 ]Faculty of Environment and Resource Studies, Mahidol University, 999 Phuttamonthon 4 Rd., Phuttamonthon District, Nakhon Pathom 73170, Thailand
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: seoyr@ 123456dongguk.edu ; Tel.: +82-31-961-5172.
                Article
                ijms-16-12261
                10.3390/ijms160612261
                4490443
                26035755
                700944be-b536-4a93-a4c7-9872ed9db4a5
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 March 2015
                : 15 May 2015
                Categories
                Review

                Molecular biology
                water flea,daphnia spp.,ecological risk assessment,ecotoxicogenomics,predictive toxicology

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