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Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis

Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using t...

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Autores principales: Antonucci, Salvatore, Mulvey, John F., Burger, Nils, Di Sante, Moises, Hall, Andrew R., Hinchy, Elizabeth C., Caldwell, Stuart T., Gruszczyk, Anja V., Deshwal, Soni, Hartley, Richard C., Kaludercic, Nina, Murphy, Michael P., Di Lisa, Fabio, Krieg, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607027/
https://www.ncbi.nlm.nih.gov/pubmed/30731114
http://dx.doi.org/10.1016/j.freeradbiomed.2019.01.034
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author Antonucci, Salvatore
Mulvey, John F.
Burger, Nils
Di Sante, Moises
Hall, Andrew R.
Hinchy, Elizabeth C.
Caldwell, Stuart T.
Gruszczyk, Anja V.
Deshwal, Soni
Hartley, Richard C.
Kaludercic, Nina
Murphy, Michael P.
Di Lisa, Fabio
Krieg, Thomas
author_facet Antonucci, Salvatore
Mulvey, John F.
Burger, Nils
Di Sante, Moises
Hall, Andrew R.
Hinchy, Elizabeth C.
Caldwell, Stuart T.
Gruszczyk, Anja V.
Deshwal, Soni
Hartley, Richard C.
Kaludercic, Nina
Murphy, Michael P.
Di Lisa, Fabio
Krieg, Thomas
author_sort Antonucci, Salvatore
collection PubMed
description Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca(2+)] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic.
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spelling pubmed-66070272019-07-15 Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis Antonucci, Salvatore Mulvey, John F. Burger, Nils Di Sante, Moises Hall, Andrew R. Hinchy, Elizabeth C. Caldwell, Stuart T. Gruszczyk, Anja V. Deshwal, Soni Hartley, Richard C. Kaludercic, Nina Murphy, Michael P. Di Lisa, Fabio Krieg, Thomas Free Radic Biol Med Article Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca(2+)] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic. Elsevier Science 2019-04 /pmc/articles/PMC6607027/ /pubmed/30731114 http://dx.doi.org/10.1016/j.freeradbiomed.2019.01.034 Text en © The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Antonucci, Salvatore
Mulvey, John F.
Burger, Nils
Di Sante, Moises
Hall, Andrew R.
Hinchy, Elizabeth C.
Caldwell, Stuart T.
Gruszczyk, Anja V.
Deshwal, Soni
Hartley, Richard C.
Kaludercic, Nina
Murphy, Michael P.
Di Lisa, Fabio
Krieg, Thomas
Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title_full Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title_fullStr Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title_full_unstemmed Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title_short Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
title_sort selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607027/
https://www.ncbi.nlm.nih.gov/pubmed/30731114
http://dx.doi.org/10.1016/j.freeradbiomed.2019.01.034
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