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Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells
Exposure to the endocrine disruptor bisphenol A (BPA) has been linked with immune disorders and increased tumour risk. Our previous work in activated human peripheral blood mononuclear cells demonstrated that exposure to “low-dose” BPA diminished telomerase activity via an ER/GPR30-ERK signalling pa...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519100/ https://www.ncbi.nlm.nih.gov/pubmed/32978426 http://dx.doi.org/10.1038/s41598-020-72546-x |
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author | Tran, Hoai Thi Thu Herz, Corinna Lamy, Evelyn |
author_facet | Tran, Hoai Thi Thu Herz, Corinna Lamy, Evelyn |
author_sort | Tran, Hoai Thi Thu |
collection | PubMed |
description | Exposure to the endocrine disruptor bisphenol A (BPA) has been linked with immune disorders and increased tumour risk. Our previous work in activated human peripheral blood mononuclear cells demonstrated that exposure to “low-dose” BPA diminished telomerase activity via an ER/GPR30-ERK signalling pathway. Leukocyte telomerase activity and telomere maintenance are crucial for normal immune function and homeostasis. We thus here further studied the effects of BPA on human T cell subpopulations. Exposure to 0.3–3 nM BPA, i. e. at doses in the realm of human exposure, notably reduced telomerase activity in activated CD8 + T but not CD4 + T cells in a non-monotonic response pattern as determined by the TRAP-ELISA assay. Under long-term BPA exposure, significant telomere length shortening, reduction in mitochondrial DNA copy number, cell proliferation and IFN-γ as well as hTERT protein suppression could be observed in CD8 + lymphocytes, as analysed by qRT-PCR, flow cytometry and western blot analysis. This study extends our previous in vitro findings that “low-dose” BPA has potential negative effects on healthy human cytotoxic T cell response. These results might merit some special attention to further investigate chronic BPA exposure in the context of adaptive immune response dysfunction and early onset of cancer in man. |
format | Online Article Text |
id | pubmed-7519100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75191002020-09-29 Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells Tran, Hoai Thi Thu Herz, Corinna Lamy, Evelyn Sci Rep Article Exposure to the endocrine disruptor bisphenol A (BPA) has been linked with immune disorders and increased tumour risk. Our previous work in activated human peripheral blood mononuclear cells demonstrated that exposure to “low-dose” BPA diminished telomerase activity via an ER/GPR30-ERK signalling pathway. Leukocyte telomerase activity and telomere maintenance are crucial for normal immune function and homeostasis. We thus here further studied the effects of BPA on human T cell subpopulations. Exposure to 0.3–3 nM BPA, i. e. at doses in the realm of human exposure, notably reduced telomerase activity in activated CD8 + T but not CD4 + T cells in a non-monotonic response pattern as determined by the TRAP-ELISA assay. Under long-term BPA exposure, significant telomere length shortening, reduction in mitochondrial DNA copy number, cell proliferation and IFN-γ as well as hTERT protein suppression could be observed in CD8 + lymphocytes, as analysed by qRT-PCR, flow cytometry and western blot analysis. This study extends our previous in vitro findings that “low-dose” BPA has potential negative effects on healthy human cytotoxic T cell response. These results might merit some special attention to further investigate chronic BPA exposure in the context of adaptive immune response dysfunction and early onset of cancer in man. Nature Publishing Group UK 2020-09-25 /pmc/articles/PMC7519100/ /pubmed/32978426 http://dx.doi.org/10.1038/s41598-020-72546-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Tran, Hoai Thi Thu Herz, Corinna Lamy, Evelyn Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title | Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title_full | Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title_fullStr | Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title_full_unstemmed | Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title_short | Long-term exposure to “low-dose” bisphenol A decreases mitochondrial DNA copy number, and accelerates telomere shortening in human CD8 + T cells |
title_sort | long-term exposure to “low-dose” bisphenol a decreases mitochondrial dna copy number, and accelerates telomere shortening in human cd8 + t cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519100/ https://www.ncbi.nlm.nih.gov/pubmed/32978426 http://dx.doi.org/10.1038/s41598-020-72546-x |
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