McNeill, Rhiannon Victoria, Mason, Andrew Stephen orcid.org/0000-0002-8222-3974, Hodson, Mark Edward orcid.org/0000-0002-8166-1526 et al. (2 more authors) (2019) Specificity of the Metallothionein-1 Response by Cadmium-Exposed Human Urothelial Cells. International Journal of Molecular Sciences. ISSN 1422-0067
Abstract
Occupational and environmental exposure to cadmium is associated with the development of urothelial cancer. The metallothionein (MT) family of genes encodes proteins that sequester metal ions and modulate physiological processes, including zinc homeostasis. Little is known about the selectivity of expression of the different MT isoforms. Here, we examined the effect of cadmium exposure on MT gene and isoform expression by normal human urothelial (NHU) cell cultures. Baseline and cadmium-induced MT gene expression was characterized by next generation sequencing and RT-PCR; protein expression was assessed by western blotting using isoform specific antibodies. Expression of the zinc transporter-1 (SLC30A1) gene was also assessed. NHU cells displayed transcription of MT-2A, but neither MT-3 nor MT-4 genes. Most striking was a highly inducer-specific expression of MT-1 genes, with cadmium inducing transcription of MT-1A, MT-1G, MT-1H and MT-1M. Whereas MT-1G was also induced by zinc and nickel ions and MT-1H by iron, both MT-1A and MT-1M were highly cadmium-specific, which was confirmed for protein using isoform-specific antibodies. Protein but not transcript endured post exposure, probably reflecting sequestration. SLC30A1 transcription was also affected by cadmium ion exposure, potentially reflecting perturbation of intracellular zinc homeostasis. We conclude that human urothelium displays a highly inductive profile of MT-1 gene expression, with two isoforms identified as highly specific to cadmium providing candidate transcript and long-lived protein biomarkers of cadmium exposure
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) The University of York > Faculty of Sciences (York) > Environment and Geography (York) The University of York > Faculty of Sciences (York) > Biology (York) > Jack Birch Unit for Molecular Carcinogenesis (York) |
Depositing User: | Pure (York) |
Date Deposited: | 13 Mar 2019 12:10 |
Last Modified: | 31 Oct 2024 01:00 |
Published Version: | https://doi.org/10.3390/ijms20061344 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.3390/ijms20061344 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:143632 |
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Filename: Southgate_Int_J_Mol_Sci_Manuscript_Revised_for_Reviewers_Comments_Round_2_12.03.19.pdf
Description: Southgate - Int J Mol Sci Manuscript Revised for Reviewers' Comments Round 2 12.03.19