Kainate-induced mitochondrial oxidative stress contributes to hippocampal degeneration in senescence-accelerated mice

Eun Joo Shin, Ji Hoon Jeong, Guoying Bing, Eon Sub Park, Jong Seok Chae, Tran Phi Hoang Yen, Won Ki Kim, Myung Bok Wie, Bae Dong Jung, Hyun Ji Kim, Sung Youl Lee, Hyoung Chun Kim

    Research output: Contribution to journalArticlepeer-review

    45 Citations (Scopus)

    Abstract

    We have demonstrated that kainate (KA) induces a reduction in mitochondrial Mn-superoxide dismutase (Mn-SOD) expression in the rat hippocampus and that KA-induced oxidative damage is more prominent in senile-prone (SAM-P8) than senile-resistant (SAM-R1) mice. To extend this, we examined whether KA seizure sensitivity contributed to mitochondrial degeneration in these mouse strains. KA-induced seizure susceptibility in SAM-P8 mice paralleled prominent increases in lipid peroxidation and protein oxidation and was accompanied by significant impairment in glutathione homeostasis in the hippocampus. These findings were more pronounced in the mitochondrial fraction than in the hippocampal homogenate. Consistently, KA-induced decreases in Mn-SOD protein expression, mitochondrial transmembrane potential, and uncoupling protein (UCP)-2 expression were more prominent in SAM-P8 than SAM-R1 mice. Marked release of cytochrome c from mitochondria into the cytosol and a higher level of caspase-3 cleavage were observed in KA-treated SAM-P8 mice. Additionally, electron microscopic evaluation indicated that KA-induced increases in mitochondrial damage and lipofuscin-like substances were more pronounced in SAM-P8 than SAM-R1 animals. These results suggest that KA-mediated mitochondrial oxidative stress contributed to hippocampal degeneration in the senile-prone mouse.

    Original languageEnglish
    Pages (from-to)645-658
    Number of pages14
    JournalCellular Signalling
    Volume20
    Issue number4
    DOIs
    Publication statusPublished - 2008 Apr

    Bibliographical note

    Funding Information:
    This study was supported by a grant of the Korea Health 21 R&D Project (A020007), Ministry of Health & Welfare, Republic of Korea, by a grant (M103KV010014-07K2201-01410) from the Brain Research Center from the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, and by Brain Korea 21 project. Equipment at the Institute of Pharmaceutical Science (Kangwon National University) and Korea Basic Science Institute, Chunchon Center were used for this study. The English language in this article has been checked by at least two professional editors, both native speakers of English. For a certificate, see: http://www.textcheck.com/cgi-bin/certificate.cgi?id=T00dnb .

    Keywords

    • Hippocampus
    • Kainate
    • Mitochondria
    • Oxidative stress
    • Seizures
    • Senescence-accelerated mice

    ASJC Scopus subject areas

    • Cell Biology

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