Sirtuin3 Protected Against Neuronal Damage and Cycled into Nucleus in Status Epilepticus Model

Abstract

In pathological conditions such as status epilepticus (SE), neuronal cell death can occur due to oxidative stress that is caused by an excessive production and accumulation of reactive oxygen species (ROS). Sirtuin3 (Sirt3) plays an important role in maintaining appropriate ROS levels by regulating manganese superoxide dismutase (MnSOD), which scavenges ROS in mitochondria. Using a SE model, we demonstrated that Sirt3 directly regulated MnSOD activity by deacetylation, which protects hippocampal cells against damage from ROS. Furthermore, we showed that after formation in the nucleus, Sirt3 is primarily located in the mitochondria, where it is activated and exerts its major function. Sirt3 then completed its pathway and moved back into the nucleus. Our data indicate that Sirt3 has an important function in regulating MnSOD, which results in decreased ROS in hippocampal cells. Sirt3 may have potential as an effective therapeutic target in SE conditions that would delay the progression of epileptogenesis.