STATUS EPILEPTICUS STIMULATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR γ COACTIVATOR 1-α/MITOCHONDRIAL ANTIOXIDANT SYSTEM PATHWAY BY A NITRIC OXIDE-DEPENDENT MECHANISM

Peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC-1 alpha) is a transcriptional coactivator identified as an upstream regulator of lipid catabolism, mitochondrial number and function. PGC-1 alpha protects neurons against oxidative damage by inducing several members of the mitochondrial antioxidant system such as superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Its role in seizure-induced oxidative stress has not been studied. Here we showed that pilocarpine-induced status epilepticus (SE) stimulates the PGC-1 alpha/mitochondrial antioxidant system signaling pathway in the rat hippocampus. Because nitric oxide (NO) is the key factor of mitochondrial biogenesis through the transcriptional induction of PGC-1 alpha, we investigated whether NO is involved in activation of the PGC-1 alpha/mitochondrial antioxidant system after SE. Treatment with the NO synthase (NOS) inhibitor N(G)-nitro-L-argininemethyl ester (L-NAME) attenuated the increased expression of the PGC-1 alpha/mitochondrial antioxidant system after SE and enhanced oxidative stress. These results suggest that SE can induce the PGC-1 alpha/mitochondrial antioxidant system signaling pathway, which may represent a protective mechanism against SE-induced oxidative stress. Furthermore, NO may positively regulate the mitochondrial antioxidant system by inducing PGC-1 alpha in pilocarpine-induced SE. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.