title: Role of glutathione peroxidase in the ontogeny of hippocampal oxidative stress and kainate seizure sensitivity in the genetically epilepsy-prone rats.
abstract: Oxidative stress may contribute to epileptogenicity in genetic models of epilepsy. To address this, we examined the enzymatic activity of cytosolic Cu/Zn superoxide dismutase (SOD-1), mitochondrial Mn superoxide dismutase (SOD-2), and glutathione peroxidase (GPx) in the developing hippocampus of genetically epilepsy-prone rats (GEPR-9s). We also measured changes in the GSH/GSSG ratio, lipid peroxidation, and protein oxidation at post-natal days (PD) 7, 30, and 90, respectively. Compared with control Sprague-Dawley (SD) rats, GEPR-9s showed similar SOD-1 and SOD-2 activity but lower GPx activity. Epilepsy-prone rats also showed lower GSH/GSSG ratios than controls, and more lipid peroxidation (as measured by malondialdehyde levels) and protein oxidation (as measured by carbonyl levels). Treatment with kainic acid (KA) resulted in more pronounced seizures, less GPx activity, and lower GSH/GSSG ratios in GEPR-9s than in controls, but KA did not significantly affect SOD-1 or SOD-2 activity, suggesting that GEPR-9s do not compensate for reduced GPx activity by increasing SOD. Moreover, KA treatment resulted in significantly a lower GSH/GSSG ratio and GPx-like immunoreactivity and higher malondialdehyde and carbonyl levels in GEPR-9s than in controls. These findings were more evident in GEPR-9s at PD 90 than at PD 30, indicating that oxidative stress is age-dependent. Double-labeling immunocytochemical analysis demonstrated co-localization of GPx-immunoreactive glia-like cells and reactive astrocytes, as labeled by glial fibrillary acidic protein (GFAP). This suggests that mobilization of astroglial cells for synthesis of GPx protein is a response to KA insult, intended to decrease the neurotoxicity induced by peroxides. These responses were more pronounced in control SD rats than in GEPR-9s. Our results suggest that impairment of the GPx (including glutathione)-mediated antioxidant system contributed to epileptogenesis in GEPR-9s.
authors.affiliation: Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon 200-701, South Korea.
authors.forename: Eun-Joo
authors.initials: EJ
authors.lastname: Shin
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Chae
authors.forename: Tran Phi Hoang
authors.initials: TP
authors.lastname: Yen
authors.forename: Hyun Ji
authors.initials: HJ
authors.lastname: Kim
authors.forename: Myung-Bok
authors.initials: MB
authors.lastname: Wie
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004827:Epilepsy / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D005978:Glutathione; D005979:Glutathione Peroxidase; D007608:Kainic Acid; D009498:Neurotoxins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606292:Sod1 protein, rat