Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis.

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 i

SUBMITTER: Antonucci S 

PROVIDER: S-EPMC6607027 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature