Therefore, the mitochondria can be consid ered a target for potential neuroprotective strategies in epilepsy. The uncoupling proteins have emerged as important natural antioxidants in the maintenance of re active oxygen species selleck compound homeostasis. UCPs be long to a superfamily of mitochondrial anion transporters that uncouple ATP synthesis from oxidative phosphoryl ation by causing proton leakage across the mitochondrial inner membrane, leading to energy dissipation and heat production. More importantly, the resultant decrease in proton electrochemical gradient across the inner mito chondrial membrane elicited by the UCPs mitigates mitochondrial ROS production. In mammals, five homologues, UCP1 to UCP5, have so far been cloned.

Among them, accumulating Inhibitors,Modulators,Libraries evidence suggests that an in crease in UCP2 gene expression is related to the decline of mitochondrial ROS production. UCP2 has been widely studied in the context of obesity, diabetes mellitus and inflammatory responses, an absence of UCP2 potentially promotes ROS accumulation and induces oxidative damages and inflammatory response. In the cen tral nervous system, UCP2 has been shown to be upregulated by stress signals such as kainate administra tion, injury or ischemia, and overexpression of UCP2 has been reported to be neuroprotective against oxidative stress in vivo and in vitro. However, the exact mechanism has not been fully established. We have shown previously that dysfunction of complex I respiratory chain enzyme and mitochondrial ultrastructural damage in the hippocampus are associated with prolonged seizure during experimental temporal lobe status epilepti cus.

Based on this animal model, our recent studies demonstrated that an excessive production of nitric oxide generated by the upregulated NO synthase II, accompanied by an increase in superoxide anion Inhibitors,Modulators,Libraries production and peroxynitrite formation, followed by a reduction in mitochondrial complex I activity and release of cytochrome c from mitochondria to the cytosol, Inhibitors,Modulators,Libraries which triggers the caspase cascades that lead to apoptotic cell death in the hippocampus. Inhibitors,Modulators,Libraries In addition to this detrimental chain reaction under status epilepticus, it is conceivable that cellular responses Inhibitors,Modulators,Libraries that counteract these detrimental effects may be activated as an endogenous protective mech anism.

In this regard, we have demonstrated previously that rosiglitazone, a peroxisome proliferator activated receptor agonist, enhances UCP2 expression after cerebral ischemia to protect against neuronal cell death in the hippocampus. It follows that as an antioxidant, www.selleckchem.com/products/Nilotinib.html UCP2 may be activated during experimental status epilepti cus, leading to decreased ROS production, reduced mito chondrial dysfunction, impeded apoptotic pathway and retarded neuronal injury in the hippocampus. Results from the present study validated this hypothesis.