Antonucci, S. et al. (2019) Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis. Free Radical Biology and Medicine, 134, pp. 678-687. (doi: 10.1016/j.freeradbiomed.2019.01.034) (PMID:30731114)
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Abstract
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 [Ca2+] 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.
Item Type: | Articles |
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Additional Information: | The work is supported by an MRC Studentship to JFM and a Wellcome Trust Investigator award to RCH (110158/Z/15/Z), the Leducq Transatlantic Network of Excellence, the COST Action EU-CARDIOPROTECTION CA16225,and the University of Padova Strategico grant (FDL). Part of the study was funded by an MRC Project Grant to TK(MR/P000320/1). |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Caldwell, Dr Stuart and Hartley, Professor Richard |
Authors: | Antonucci, S., Mulvey, J. F., Burger, N., Di Sante, M., Hall, A. R., Hinchy, E. C., Caldwell, S., Gruszczyk, A. V., Deshwal, S., Hartley, R. C., Kaludercic, N., Murphy, M. P., Di Lisa, F., and Krieg, T. |
College/School: | College of Science and Engineering > School of Chemistry |
Journal Name: | Free Radical Biology and Medicine |
Publisher: | Elsevier |
ISSN: | 0891-5849 |
ISSN (Online): | 0891-5849 |
Published Online: | 04 February 2019 |
Copyright Holders: | Copyright © 2019 Elsevier |
First Published: | First published in Free Radical Biology and Medicine 134:678-687 |
Publisher Policy: | Reproduced under a Creative Commons license |
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