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Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response
Mitochondrial functions play a central role in energy metabolism and provide survival fitness to both normal and tumor cells. Mitochondrial chaperonin Hsp60 is involved in both pro- and anti-apoptotic functions, but how Hsp60 senses the mitochondria selective oxidative stress response is unknown. In...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Libertas Academica
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767580/ https://www.ncbi.nlm.nih.gov/pubmed/24027419 http://dx.doi.org/10.4137/DTI.S12513 |
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author | Sarangi, Upasana Singh, Manish Kumar Abhijnya, Kanugovi Vijaya Vittal Reddy, Lebaka Prasanna Anjaneya Prasad, Badabagni Siva Pitke, Vikrant Vinay Paithankar, Khanderao Sreedhar, Amere Subbarao |
author_facet | Sarangi, Upasana Singh, Manish Kumar Abhijnya, Kanugovi Vijaya Vittal Reddy, Lebaka Prasanna Anjaneya Prasad, Badabagni Siva Pitke, Vikrant Vinay Paithankar, Khanderao Sreedhar, Amere Subbarao |
author_sort | Sarangi, Upasana |
collection | PubMed |
description | Mitochondrial functions play a central role in energy metabolism and provide survival fitness to both normal and tumor cells. Mitochondrial chaperonin Hsp60 is involved in both pro- and anti-apoptotic functions, but how Hsp60 senses the mitochondria selective oxidative stress response is unknown. In this study, by using rotenone, an irreversible inhibitor of oxidative phosphorylation against IMR-32 and BC-8 tumor cells containing differential heat shock transcriptional machinery, we studied whether the oxidative stress response is related to Hsp60. The accelerated cytotoxicity in response to rotenone has been correlated with enhanced production of O(2)(•−), H(2)O(2), reactive oxygen species, and Hsp60 translocation from the mitochondria to the cytoplasm. The inability of cells to resist oxidative stress mediated Hsp60 translocation appeared to depend on mitochondrial oxyradical scavenging system and Bax translocation. A delayed oxidative stress response in hsp60 shRNA-treated cells was found to be due to increased mitochondrial translocation of Hsp60 on shRNA pre-sensitization. Overexpression of Hsp60 failed to protect cells from oxidative stress due to a lack of its mitochondrial retention upon post-rotenone treatment. These results also revealed that Hsp60 mitochondrial localization is indispensable for decreasing O(2)(•−) levels, but not H(2)O(2) and ROS levels. However, cycloheximide treatment alone induced Hsp60 translocation, while rotenone combination delayed this translocation. In contrast to oxidative stress, MG132 and 17AAG treatments showed mitochondrial retention of Hsp60; however, MG132 combination either with hsp60 shRNA or 17AAG induced its translocation. Additionally, overexpression of Huntingtin gene also resulted in Hsp60 mitochondrial accumulation. We suggest that Hsp60 may act as a barrier to pharmacological targeting of mitochondria. |
format | Online Article Text |
id | pubmed-3767580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Libertas Academica |
record_format | MEDLINE/PubMed |
spelling | pubmed-37675802013-09-11 Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response Sarangi, Upasana Singh, Manish Kumar Abhijnya, Kanugovi Vijaya Vittal Reddy, Lebaka Prasanna Anjaneya Prasad, Badabagni Siva Pitke, Vikrant Vinay Paithankar, Khanderao Sreedhar, Amere Subbarao Drug Target Insights Original Research Mitochondrial functions play a central role in energy metabolism and provide survival fitness to both normal and tumor cells. Mitochondrial chaperonin Hsp60 is involved in both pro- and anti-apoptotic functions, but how Hsp60 senses the mitochondria selective oxidative stress response is unknown. In this study, by using rotenone, an irreversible inhibitor of oxidative phosphorylation against IMR-32 and BC-8 tumor cells containing differential heat shock transcriptional machinery, we studied whether the oxidative stress response is related to Hsp60. The accelerated cytotoxicity in response to rotenone has been correlated with enhanced production of O(2)(•−), H(2)O(2), reactive oxygen species, and Hsp60 translocation from the mitochondria to the cytoplasm. The inability of cells to resist oxidative stress mediated Hsp60 translocation appeared to depend on mitochondrial oxyradical scavenging system and Bax translocation. A delayed oxidative stress response in hsp60 shRNA-treated cells was found to be due to increased mitochondrial translocation of Hsp60 on shRNA pre-sensitization. Overexpression of Hsp60 failed to protect cells from oxidative stress due to a lack of its mitochondrial retention upon post-rotenone treatment. These results also revealed that Hsp60 mitochondrial localization is indispensable for decreasing O(2)(•−) levels, but not H(2)O(2) and ROS levels. However, cycloheximide treatment alone induced Hsp60 translocation, while rotenone combination delayed this translocation. In contrast to oxidative stress, MG132 and 17AAG treatments showed mitochondrial retention of Hsp60; however, MG132 combination either with hsp60 shRNA or 17AAG induced its translocation. Additionally, overexpression of Huntingtin gene also resulted in Hsp60 mitochondrial accumulation. We suggest that Hsp60 may act as a barrier to pharmacological targeting of mitochondria. Libertas Academica 2013-09-01 /pmc/articles/PMC3767580/ /pubmed/24027419 http://dx.doi.org/10.4137/DTI.S12513 Text en © 2013 the author(s), publisher and licensee Libertas Academica Ltd. This is an open access article published under the Creative Commons CC-BY-NC 3.0 license. |
spellingShingle | Original Research Sarangi, Upasana Singh, Manish Kumar Abhijnya, Kanugovi Vijaya Vittal Reddy, Lebaka Prasanna Anjaneya Prasad, Badabagni Siva Pitke, Vikrant Vinay Paithankar, Khanderao Sreedhar, Amere Subbarao Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title | Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title_full | Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title_fullStr | Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title_full_unstemmed | Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title_short | Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response |
title_sort | hsp60 chaperonin acts as barrier to pharmacologically induced oxidative stress mediated apoptosis in tumor cells with differential stress response |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767580/ https://www.ncbi.nlm.nih.gov/pubmed/24027419 http://dx.doi.org/10.4137/DTI.S12513 |
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