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PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation
Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing ‘oxidative stress’. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027479/ https://www.ncbi.nlm.nih.gov/pubmed/27198223 http://dx.doi.org/10.1093/nar/gkw442 |
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author | Andersson, Anneli Bluwstein, Andrej Kumar, Nitin Teloni, Federico Traenkle, Jens Baudis, Michael Altmeyer, Matthias Hottiger, Michael O. |
author_facet | Andersson, Anneli Bluwstein, Andrej Kumar, Nitin Teloni, Federico Traenkle, Jens Baudis, Michael Altmeyer, Matthias Hottiger, Michael O. |
author_sort | Andersson, Anneli |
collection | PubMed |
description | Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing ‘oxidative stress’. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H(2)O(2) was mediated by the PLC/IP3R/Ca(2+)/PKCα signaling axis. Mechanistically, H(2)O(2)-induced PAR formation correlated with Ca(2+)-dependent DNA damage, which, however, was PKCα-independent. In contrast, PAR formation was completely lost upon knockdown of PKCα, suggesting that DNA damage alone was not sufficient for inducing PAR formation, but required a PKCα-dependent process. Intriguingly, the loss of PAR formation observed upon PKCα depletion was overcome when the chromatin structure-modifying protein HMGB1 was co-depleted with PKCα, suggesting that activation and nuclear translocation of PKCα releases the inhibitory effect of HMGB1 on PAR formation. Together, these results identify PKCα and HMGB1 as important co-regulators involved in H(2)O(2)-induced PAR formation, a finding that may have important relevance for oxidative stress-associated pathophysiological conditions. |
format | Online Article Text |
id | pubmed-5027479 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50274792016-09-21 PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation Andersson, Anneli Bluwstein, Andrej Kumar, Nitin Teloni, Federico Traenkle, Jens Baudis, Michael Altmeyer, Matthias Hottiger, Michael O. Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Harmful oxidation of proteins, lipids and nucleic acids is observed when reactive oxygen species (ROS) are produced excessively and/or the antioxidant capacity is reduced, causing ‘oxidative stress’. Nuclear poly-ADP-ribose (PAR) formation is thought to be induced in response to oxidative DNA damage and to promote cell death under sustained oxidative stress conditions. However, what exactly triggers PAR induction in response to oxidative stress is incompletely understood. Using reverse phase protein array (RPPA) and in-depth analysis of key stress signaling components, we observed that PAR formation induced by H(2)O(2) was mediated by the PLC/IP3R/Ca(2+)/PKCα signaling axis. Mechanistically, H(2)O(2)-induced PAR formation correlated with Ca(2+)-dependent DNA damage, which, however, was PKCα-independent. In contrast, PAR formation was completely lost upon knockdown of PKCα, suggesting that DNA damage alone was not sufficient for inducing PAR formation, but required a PKCα-dependent process. Intriguingly, the loss of PAR formation observed upon PKCα depletion was overcome when the chromatin structure-modifying protein HMGB1 was co-depleted with PKCα, suggesting that activation and nuclear translocation of PKCα releases the inhibitory effect of HMGB1 on PAR formation. Together, these results identify PKCα and HMGB1 as important co-regulators involved in H(2)O(2)-induced PAR formation, a finding that may have important relevance for oxidative stress-associated pathophysiological conditions. Oxford University Press 2016-09-19 2016-05-19 /pmc/articles/PMC5027479/ /pubmed/27198223 http://dx.doi.org/10.1093/nar/gkw442 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Andersson, Anneli Bluwstein, Andrej Kumar, Nitin Teloni, Federico Traenkle, Jens Baudis, Michael Altmeyer, Matthias Hottiger, Michael O. PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title | PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title_full | PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title_fullStr | PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title_full_unstemmed | PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title_short | PKCα and HMGB1 antagonistically control hydrogen peroxide-induced poly-ADP-ribose formation |
title_sort | pkcα and hmgb1 antagonistically control hydrogen peroxide-induced poly-adp-ribose formation |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027479/ https://www.ncbi.nlm.nih.gov/pubmed/27198223 http://dx.doi.org/10.1093/nar/gkw442 |
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