Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.