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Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide
To examine the role of intracellular labile iron pool (LIP), ferritin (Ft), and antioxidant defence in cellular resistance to oxidative stress on chronic adaptation, a new H(2)O(2)-resistant Jurkat T cell line “HJ16” was developed by gradual adaptation of parental “J16” cells to high concentrations...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046229/ https://www.ncbi.nlm.nih.gov/pubmed/24333634 http://dx.doi.org/10.1016/j.freeradbiomed.2013.12.006 |
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author | Al-Qenaei, Abdullah Yiakouvaki, Anthie Reelfs, Olivier Santambrogio, Paolo Levi, Sonia Hall, Nick D. Tyrrell, Rex M. Pourzand, Charareh |
author_facet | Al-Qenaei, Abdullah Yiakouvaki, Anthie Reelfs, Olivier Santambrogio, Paolo Levi, Sonia Hall, Nick D. Tyrrell, Rex M. Pourzand, Charareh |
author_sort | Al-Qenaei, Abdullah |
collection | PubMed |
description | To examine the role of intracellular labile iron pool (LIP), ferritin (Ft), and antioxidant defence in cellular resistance to oxidative stress on chronic adaptation, a new H(2)O(2)-resistant Jurkat T cell line “HJ16” was developed by gradual adaptation of parental “J16” cells to high concentrations of H(2)O(2). Compared to J16 cells, HJ16 cells exhibited much higher resistance to H(2)O(2)-induced oxidative damage and necrotic cell death (up to 3 mM) and had enhanced antioxidant defence in the form of significantly higher intracellular glutathione and mitochondrial ferritin (FtMt) levels as well as higher glutathione-peroxidase (GPx) activity. In contrast, the level of the Ft H-subunit (FtH) in the H(2)O(2)-adapted cell line was found to be 7-fold lower than in the parental J16 cell line. While H(2)O(2) concentrations higher than 0.1 mM fully depleted the glutathione content of J16 cells, in HJ16 cells the same treatments decreased the cellular glutathione content to only half of the original value. In HJ16 cells, H(2)O(2) concentrations higher than 0.1 mM increased the level of FtMt up to 4-fold of their control values but had no effect on the FtMt levels in J16 cells. Furthermore, while the basal cytosolic level of LIP was similar in both cell lines, H(2)O(2) treatment substantially increased the cytosolic LIP levels in J16 but not in HJ16 cells. H(2)O(2) treatment also substantially decreased the FtH levels in J16 cells (up to 70% of the control value). In contrast in HJ16 cells, FtH levels were not affected by H(2)O(2) treatment. These results indicate that chronic adaptation of J16 cells to high concentrations of H(2)O(2) has provoked a series of novel and specific cellular adaptive responses that contribute to higher resistance of HJ16 cells to oxidative damage and cell death. These include increased cellular antioxidant defence in the form of higher glutathione and FtMt levels, higher GPx activity, and lower FtH levels. Further adaptive responses include the significantly reduced cellular response to oxidant-mediated glutathione depletion, FtH modulation, and labile iron release and a significant increase in FtMt levels following H(2)O(2) treatment. |
format | Online Article Text |
id | pubmed-4046229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40462292014-06-06 Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide Al-Qenaei, Abdullah Yiakouvaki, Anthie Reelfs, Olivier Santambrogio, Paolo Levi, Sonia Hall, Nick D. Tyrrell, Rex M. Pourzand, Charareh Free Radic Biol Med Original Contribution To examine the role of intracellular labile iron pool (LIP), ferritin (Ft), and antioxidant defence in cellular resistance to oxidative stress on chronic adaptation, a new H(2)O(2)-resistant Jurkat T cell line “HJ16” was developed by gradual adaptation of parental “J16” cells to high concentrations of H(2)O(2). Compared to J16 cells, HJ16 cells exhibited much higher resistance to H(2)O(2)-induced oxidative damage and necrotic cell death (up to 3 mM) and had enhanced antioxidant defence in the form of significantly higher intracellular glutathione and mitochondrial ferritin (FtMt) levels as well as higher glutathione-peroxidase (GPx) activity. In contrast, the level of the Ft H-subunit (FtH) in the H(2)O(2)-adapted cell line was found to be 7-fold lower than in the parental J16 cell line. While H(2)O(2) concentrations higher than 0.1 mM fully depleted the glutathione content of J16 cells, in HJ16 cells the same treatments decreased the cellular glutathione content to only half of the original value. In HJ16 cells, H(2)O(2) concentrations higher than 0.1 mM increased the level of FtMt up to 4-fold of their control values but had no effect on the FtMt levels in J16 cells. Furthermore, while the basal cytosolic level of LIP was similar in both cell lines, H(2)O(2) treatment substantially increased the cytosolic LIP levels in J16 but not in HJ16 cells. H(2)O(2) treatment also substantially decreased the FtH levels in J16 cells (up to 70% of the control value). In contrast in HJ16 cells, FtH levels were not affected by H(2)O(2) treatment. These results indicate that chronic adaptation of J16 cells to high concentrations of H(2)O(2) has provoked a series of novel and specific cellular adaptive responses that contribute to higher resistance of HJ16 cells to oxidative damage and cell death. These include increased cellular antioxidant defence in the form of higher glutathione and FtMt levels, higher GPx activity, and lower FtH levels. Further adaptive responses include the significantly reduced cellular response to oxidant-mediated glutathione depletion, FtH modulation, and labile iron release and a significant increase in FtMt levels following H(2)O(2) treatment. Elsevier Science 2014-03 /pmc/articles/PMC4046229/ /pubmed/24333634 http://dx.doi.org/10.1016/j.freeradbiomed.2013.12.006 Text en © 2013 Elsevier Inc. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Original Contribution Al-Qenaei, Abdullah Yiakouvaki, Anthie Reelfs, Olivier Santambrogio, Paolo Levi, Sonia Hall, Nick D. Tyrrell, Rex M. Pourzand, Charareh Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title | Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title_full | Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title_fullStr | Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title_full_unstemmed | Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title_short | Role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted Jurkat T cells to hydrogen peroxide |
title_sort | role of intracellular labile iron, ferritin, and antioxidant defence in resistance of chronically adapted jurkat t cells to hydrogen peroxide |
topic | Original Contribution |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046229/ https://www.ncbi.nlm.nih.gov/pubmed/24333634 http://dx.doi.org/10.1016/j.freeradbiomed.2013.12.006 |
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