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 journalArticle

33 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 1

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Shin, E. J., Jeong, J. H., Bing, G., Park, E. S., Chae, J. S., Yen, T. P. H., Kim, W-K., Wie, M. B., Jung, B. D., Kim, H. J., Lee, S. Y., & Kim, H. C. (2008). Kainate-induced mitochondrial oxidative stress contributes to hippocampal degeneration in senescence-accelerated mice. Cellular Signalling, 20(4), 645-658. https://doi.org/10.1016/j.cellsig.2007.11.014