Antonucci 2019 Free Radic Biol Med
|Antonucci S, Mulvey JF, Burger N, Di Sante M, Hall AR, Hinchy EC, Caldwell ST, Gruszczyk AV, Deshwal S, Hartley RC, Kaludercic N, Murphy MP, Di Lisa F, Krieg T (2019) Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis. Free Radic Biol Med 134:678-687.|
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.
• Keywords: Mitochondria, Reactive Oxygen Species, Ischaemia/Reperfusion injury • Bioblast editor: Sobotka O
Labels: Pathology: Cardiovascular Stress:Ischemia-reperfusion, Oxidative stress;RONS, Hypoxia Organism: Rat