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Identification of potential molecular biomarkers in response to thioredoxin reductase 1 deficiency under nickel exposure

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Abstract

Nickel (II) is a ubiquitous environmental contaminant and it is known to be a highly toxic metal. The level of nickel in the environment has been raised with advances in industrialization and the role of nickel in human diseases is of increasing concern. Thioredoxin reductase 1 (Trr 1) is one of major redox factors having a potential role in cellular defense system against exposure to environmental toxicants. In this study, we investigated the protective roles of the Trr 1 against nickel-induced DNA damage. We found significantly higher amounts of DNA strand break in Trr 1 silencing cells compared to Trr 1 wild-type cells under nickel exposure, using γ-H2AX immunofluorescence staining. We also identified the potential molecular biomarkers that participated in gene-environment interaction between Trr 1 deficiency and nickel exposure via microarray analysis. In particular, seven upregulated genes (AHNAK, FZR1, LGALS7, PLD1, PPM1F, RHOB and SFRP1) and three down-regulated genes (IFITM1, MAPK8 and RCN1), whose functions are principally in toxicity-prone as well as cytoprotection processes, including cell proliferation, cell survival, apoptosis, inflammation and DNA repair. Our findings demonstrate gene-environment interaction between Trr 1 deficiency and nickel-induced toxicity, as evidence that insufficient of redox factor Trr 1 accelerated DNA lesions caused by nickel exposure. These results suggest that the candidate genes might be further useful in the establishment of Trr 1-mediated strategies by which modulate cellular defense against environmental toxicants, nickel.

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Authors and Affiliations

  1. Department of Life Science, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul, 100-715, Korea

    Hye Lim Kim & Young Rok Seo

  2. Institute of Environmental Medicine for Green Chemistry, Dongguk University, 30 Pildong-ro 1-gil, Jung-gu, Seoul, 100-715, Korea

    Hye Lim Kim & Young Rok Seo

  3. Department of Pharmacology, Institute for Biomedical Science Institute (IBMS), School of Medicine, Kyung Hee University, Seoul, 130-701, Korea

    Hye Lim Kim & Young Rok Seo

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  1. Hye Lim Kim
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Correspondence to Young Rok Seo.

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Kim, H.L., Seo, Y.R. Identification of potential molecular biomarkers in response to thioredoxin reductase 1 deficiency under nickel exposure. BioChip J 6, 157–164 (2012). https://doi.org/10.1007/s13206-012-6208-2

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  • DOI: https://doi.org/10.1007/s13206-012-6208-2

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