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

doi:10.1016/j.cellsig.2007.11.014

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

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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 language	English
Pages (from-to)	645-658
Number of pages	14
Journal	Cellular Signalling
Volume	20
Issue number	4
DOIs	https://doi.org/10.1016/j.cellsig.2007.11.014
Publication status	Published - 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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10.1016/j.cellsig.2007.11.014

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@article{132d1bc831be40a58c48b40052aaf997,

title = "Kainate-induced mitochondrial oxidative stress contributes to hippocampal degeneration in senescence-accelerated mice",

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.",

keywords = "Hippocampus, Kainate, Mitochondria, Oxidative stress, Seizures, Senescence-accelerated mice",

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

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 .",

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doi = "10.1016/j.cellsig.2007.11.014",

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T1 - Kainate-induced mitochondrial oxidative stress contributes to hippocampal degeneration in senescence-accelerated mice

AU - Shin, Eun Joo

AU - Jeong, Ji Hoon

AU - Bing, Guoying

AU - Park, Eon Sub

AU - Chae, Jong Seok

AU - Yen, Tran Phi Hoang

AU - Kim, Won Ki

AU - Wie, Myung Bok

AU - Jung, Bae Dong

AU - Kim, Hyun Ji

AU - Lee, Sung Youl

AU - Kim, Hyoung Chun

N1 - 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 .

PY - 2008/4

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N2 - 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.

AB - 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.

KW - Hippocampus

KW - Kainate

KW - Mitochondria

KW - Oxidative stress

KW - Seizures

KW - Senescence-accelerated mice

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SN - 0898-6568

VL - 20

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JF - Cellular Signalling

IS - 4

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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