0200: N-Acetylcystein protects mitochondrial function of myoblasts against statin-induced apoptosis by triggering a mitohormesis mechanism

Abstract

Although statins are the most widely used cholesterol-lowering agents for prevention of obstructive cardiovascular events, there is a risk of myopathy occurring in patients taking these drugs. The goal of our study was to show that N-Acetylcystein (NAC) triggers a mitochondrial hormesis (mitohormesis) phenomenon, able to protect the mitochondrial function from the pro-apoptotic effects of statins. We have carried on several in vitro experiments on L6 myoblasts, and studied the effects of NAC after different exposition times. Direct exposition of NAC at a concentration of 1mM inhibited the maximal mitochondrial respiration and increased H 2 O 2 production. After 24 hours of incubation, there was an increase of the reactive oxygen species (ROS) production measured by Electron Paramagnetic Resonance. This moderate oxidative stress triggered the activation of the mitochondrial biogenesis pathways after 24 hours of NAC incubation, as shown by RT-PCR. After one week of exposition, ROS production was decreased compared to control, whereas the mitochondrial content, and the maximal mitochondrial respiration were clearly increased. At the mRNA and proteins levels our results suggested an increase of antioxidant capacities after one week of NAC. Atorvastatin 100μM during 24H (ATO), increased ROS production, decreased the percentage of live cells, and increased total apoptotic cells percentage. One week NAC pretreatment decreased ROS production in presence of statins (NAC+ATO), increased the percentage of live cells, and decreased total apoptotic cells percentage compared to ATO. In conclusion, we demonstrated that NAC activates the mechanisms of mitochondrial biogenesis by increasing mitochondrial ROS production, allowing to increase the metabolic power as well as the cellular antioxidant systems The Activation of this mitohormesis phenomenon represents an interesting research field in order to protect the cells against oxidative stress. One week NAC pretreatment protects against Statins. Abstract 0200 – Figure