Increased iron-induced oxidative stress and toxicity in scrapie-infected neuroblastoma cells

The mechanisms behind the pathology of prion diseases are still unknown, but accumulating evidence suggests oxidative impairment along with metal imbalances in scrapie-infected brains. In this study, we have investigated iron-induced oxidative stress in scrapie-infected mouse neuroblastoma N2a (ScN2a) cells. Uninfected N2a and ScN2a cells were treated with ferric ammonium citrate (FAC) for 1-16 h, and the levels of labile iron pool (LIP), the formation of reactive oxygen species (ROS), cell viability and ferritin protein levels were measured. The increase in LIP in N2a cells was transient with a quick recovery to normal levels within 4 h accompanied by a moderate increase of formation of ROS after 3 h followed by the decrease to the basal level. In ScN2a cells, the increase in LIP was lower, but the process of recovery was prolonged and accompanied by high ROS formation and decreased cell viability. Ferritin protein levels were significantly lower in ScN2a cells than in wild-type cells in all iron treatments. These results suggest that ScN2a cells are more sensitive to iron treatment as compared to wild-type cells with respect to ROS formation and cell viability, and that ferritin deficiency in infected cells may contribute to iron-induced oxidative stress in scrapie-infected cells.