title: Status epilepticus stimulates peroxisome proliferator-activated receptor γ coactivator 1-α/mitochondrial antioxidant system pathway by a nitric oxide-dependent mechanism.
abstract: Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-α (PGC-1α) is a transcriptional coactivator identified as an upstream regulator of lipid catabolism, mitochondrial number and function. PGC-1α 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-1α/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-1α, we investigated whether NO is involved in activation of the PGC-1α/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-1α/mitochondrial antioxidant system after SE and enhanced oxidative stress. These results suggest that SE can induce the PGC-1α/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-1α in pilocarpine-induced SE.
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Han
authors.forename: Y T
authors.initials: YT
authors.lastname: Lin
authors.forename: J J
authors.initials: JJ
authors.lastname: Xu
authors.forename: L L
authors.initials: LL
authors.lastname: Cao
authors.forename: X W
authors.initials: XW
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Chi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D024101:Mitochondrial Proteins / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000378:metabolism* / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
chemical_list: D000975:Antioxidants; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D009569:Nitric Oxide