Mitochondrial ROS production and subsequent ERK phosphorylation are necessary for temperature preconditioning of isolated ventricular myocytes

摘要: Hypothermia and hypothermic preconditioning are known to be profoundly cardioprotective, but the molecular mechanisms of this protection have not been fully explained. In study, temperature (16 °C) was found cardioprotective in isolated adult rat ventricular myocytes, enhancing contractile recovery preventing calcium dysregulation after oxidative stress. Hypothermic preserved mitochondrial function by delaying pathological opening permeability transition pore (mPTP), whereas transient mPTP flickering remained unaltered. For first time, reactive oxygen species (ROS) from mitochondria shown released exclusively during episodes temperature-preconditioning protocol. Using a mitochondrially targeted ROS biosensor, release brief bursts 16 °C preconditioning. The scavenger N-(2-mercaptopropionyl) glycine attenuated accumulation preconditioning, abolishing protective delay opening. Temperature induces ROS-dependant phosphorylation prosurvival kinase extracellular signal-regulated (ERK)1/2. ERK1/2 activation downstream release, as presence completely blocked activation. effects on were lost inhibiting Thus, both necessary signal cardiac myocytes.