Ferritin and the response to oxidative stress

Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reac tive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron lev els. Chief among these is the sequestration of iron in ferritin. Ferritin i s a 24 subunit protein composed of two subunit types, termed H and L. The f erritin H subunit has a potent ferroxidase activity that catalyses the oxid ation of ferrous iron, whereas ferritin L plays a role in iron nucleation a nd protein stability. In the present study we report that increased synthes is of both subunits of ferritin occurs in HeLa cells exposed to oxidative s tress. An increase in the activity of iron responsive element binding prote ins in response to oxidative stress was also observed. However, this activa tion was transient, allowing ferritin protein induction to subsequently pro ceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferrit in H or ferritin L cDNA under control of a tetracycline-responsive promoter . We observed that overexpression of either ferritin H or ferritin L reduce d the accumulation of ROS in response to oxidant challenge.