Mitochondrial Superoxide Production and Oxidative Damage in the Kainic Acid Model
Abstract number :
1.113
Submission category :
Year :
2000
Submission ID :
1218
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Manisha N Patel, Ye-shih Ho, Li-Ping Liang, National Jewish Medical & Research Ctr, Denver, CO; Institute of Chemical Toxicol Wayne Univ, Detroit, MI.
RATIONALE: The objective of this study was to determine the role of mitochondrial superoxide radical-mediated oxidative damage in kainic acid-induced hippocampal damage. METHODS: Aconitase inactivation and 8-hydroxy 2-deoxyguanosine (8-OHdG) formation were used as indices of superoxide production and oxidative DNA damage, respectively. : RESULTS: Mitochondrial superoxide production and 8-OHdG formation were increased in hippocampi of rats administered kainic acid at times preceding neuronal death. Kainic acid-induced increases of mitochondrial superoxide production and hippocampal neuronal loss were attenuated in mice overexpressing mitochondrial SOD (SOD)2 or by Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a catalytic superoxide scavenger. Kainic acid-induced mitochondrial superoxide production and hippocampal cell death were exacerbated in SOD2 heterozygote knockout mice. CONCLUSIONS: These results demonstrate a role for mitochondrial superoxide production in hippocampal pathology produced by kainic acid. Supported by Parents Against Childhood Epilepsy (M.N.P.) and NIH HL56421 (Y.S.H.)