Cargando…
Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells
Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. T...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431854/ https://www.ncbi.nlm.nih.gov/pubmed/22949856 http://dx.doi.org/10.3390/ijms130810212 |
_version_ | 1782242116648304640 |
---|---|
author | Wilkinson, Sarah T. Tome, Margaret E. Briehl, Margaret M. |
author_facet | Wilkinson, Sarah T. Tome, Margaret E. Briehl, Margaret M. |
author_sort | Wilkinson, Sarah T. |
collection | PubMed |
description | Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. This suggests that adaptation to chronic oxidative stress can contribute to chemoresistance seen in lymphoma patients. Oxidative stress-resistant WEHI7.2 cell variants in a lymphoma tissue culture model exhibit a range of apoptosis sensitivities. We exploited this phenotype to test for mitochondrial changes affecting sensitivity to apoptosis in cells made resistant to oxidative stress. We identified impaired release of cytochrome c, and the intermembrane proteins adenylate kinase 2 and Smac/DIABLO, indicating inhibition of the pathway leading to permeabilization of the outer mitochondrial membrane. Blunting of a glucocorticoid-induced signal and intrinsic mitochondrial resistance to cytochrome c release contributed to both points of resistance. The level of Bcl-2 family members or a difference in Bim induction were not contributing factors. The extent of cardiolipin oxidation following dexamethasone treatment, however, did correlate with apoptosis resistance. The differences found in the variants were all proportionate to the degree of resistance to glucocorticoid treatment. We conclude that tolerance to oxidative stress leads to mitochondrial changes that confer resistance to apoptosis. |
format | Online Article Text |
id | pubmed-3431854 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-34318542012-09-04 Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells Wilkinson, Sarah T. Tome, Margaret E. Briehl, Margaret M. Int J Mol Sci Article Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. This suggests that adaptation to chronic oxidative stress can contribute to chemoresistance seen in lymphoma patients. Oxidative stress-resistant WEHI7.2 cell variants in a lymphoma tissue culture model exhibit a range of apoptosis sensitivities. We exploited this phenotype to test for mitochondrial changes affecting sensitivity to apoptosis in cells made resistant to oxidative stress. We identified impaired release of cytochrome c, and the intermembrane proteins adenylate kinase 2 and Smac/DIABLO, indicating inhibition of the pathway leading to permeabilization of the outer mitochondrial membrane. Blunting of a glucocorticoid-induced signal and intrinsic mitochondrial resistance to cytochrome c release contributed to both points of resistance. The level of Bcl-2 family members or a difference in Bim induction were not contributing factors. The extent of cardiolipin oxidation following dexamethasone treatment, however, did correlate with apoptosis resistance. The differences found in the variants were all proportionate to the degree of resistance to glucocorticoid treatment. We conclude that tolerance to oxidative stress leads to mitochondrial changes that confer resistance to apoptosis. Molecular Diversity Preservation International (MDPI) 2012-08-16 /pmc/articles/PMC3431854/ /pubmed/22949856 http://dx.doi.org/10.3390/ijms130810212 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Wilkinson, Sarah T. Tome, Margaret E. Briehl, Margaret M. Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title | Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title_full | Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title_fullStr | Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title_full_unstemmed | Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title_short | Mitochondrial Adaptations to Oxidative Stress Confer Resistance to Apoptosis in Lymphoma Cells |
title_sort | mitochondrial adaptations to oxidative stress confer resistance to apoptosis in lymphoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3431854/ https://www.ncbi.nlm.nih.gov/pubmed/22949856 http://dx.doi.org/10.3390/ijms130810212 |
work_keys_str_mv | AT wilkinsonsaraht mitochondrialadaptationstooxidativestressconferresistancetoapoptosisinlymphomacells AT tomemargarete mitochondrialadaptationstooxidativestressconferresistancetoapoptosisinlymphomacells AT briehlmargaretm mitochondrialadaptationstooxidativestressconferresistancetoapoptosisinlymphomacells |