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The Journal of Neuroscience, January 1, 1998, 18(1):205-213
Mitochondrial Susceptibility to Oxidative Stress Exacerbates
Cerebral Infarction That Follows Permanent Focal Cerebral Ischemia in
Mutant Mice with Manganese Superoxide Dismutase Deficiency
Kensuke
Murakami1,
Takeo
Kondo1,
Makoto
Kawase1, 2,
Yibing
Li1,
Shuzo
Sato1,
Sylvia F.
Chen1, and
Pak H.
Chan1, 2
1 CNS Injury and Edema Research Center, Departments of
Neurological Surgery and Neurology, University of California, School of
Medicine, San Francisco, California 94143-0651, and
2 Departments of Neurosurgery, Neurology, and Neurological
Sciences, Stanford University Medical Center, Stanford, California
94305-5784
Mitochondrial injury has been implicated in ischemic neuronal
injury. Mitochondria, producing adenosine triphosphate by virtue of
electron flow, have been shown to be both the sites of superoxide anion
(O2 ) production and the target of free
radical attacks. We evaluated these mechanisms in an in
vivo cerebral ischemia model, using mutant mice with a
heterozygous knock-out gene (Sod2  /+) encoding mitochondrial manganese superoxide dismutase (Mn-SOD).
Sod2 /+ mice demonstrated a prominent increase in
O2 production under normal
physiological conditions and in ischemia, as evidenced by specific
oxidation of a fluorescent probe, hydroethidine, reflecting decreased
activity of Mn-SOD. A mitochondrial viability assay that used rhodamine
123, which is accumulated by transmembrane potential of viable
mitochondria, demonstrated accelerated development of mitochondrial
injury. This rapid progress of ischemic injury resulted in exacerbation
of infarct size and hemisphere enlargement, causing advanced
neurological deficits but without altering DNA fragmentation induction.
The present study suggests that O2
overproduced in a mitochondrial compartment, when uncoupled from antioxidant defenses, induces impairment of mitochondrial function and
causes exacerbation of cerebral infarction after ischemia.
Key words:
cerebral ischemia; oxidative stress; manganese superoxide
dismutase; superoxide anion; mitochondrial injury; DNA
fragmentation
Copyright © 1998 Society for Neuroscience 0270-6474/98/181205-09$05.00/0
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|
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|
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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15(2):
525 - 534.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Majid, Y. Y. He, J. M. Gidday, S. S. Kaplan, E. R. Gonzales, T. S. Park, J. D. Fenstermacher, L. Wei, D. W. Choi, C. Y. Hsu, et al.
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|
|
|
|
|
|
|
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275(17):
13049 - 13055.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. HUANG, A. SHENOY, J. CUI, W. HUANG, and P. K. LIU
In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain
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February 1, 2000;
14(2):
407 - 417.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. G. Nicholls and S. L. Budd
Mitochondria and Neuronal Survival
Physiol Rev,
January 1, 2000;
80(1):
315 - 360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Ginsberg
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Arterioscler. Thromb. Vasc. Biol.,
November 1, 1999;
19(11):
2581 - 2583.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Kawase, K. Murakami, M. Fujimura, Y. Morita-Fujimura, Y. Gasche, T. Kondo, R. W. Scott, P. H. Chan, and M. S. Wolin
Exacerbation of Delayed Cell Injury After Transient Global Ischemia in Mutant Mice With CuZn Superoxide Dismutase Deficiency • Editorial Comment
Stroke,
September 1, 1999;
30(9):
1962 - 1968.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Fujimura, Y. Morita-Fujimura, M. Kawase, J.-C. Copin, B. Calagui, C. J. Epstein, and P. H. Chan
Manganese Superoxide Dismutase Mediates the Early Release of Mitochondrial Cytochrome C and Subsequent DNA Fragmentation after Permanent Focal Cerebral Ischemia in Mice
J. Neurosci.,
May 1, 1999;
19(9):
3414 - 3422.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. H. Chan, M. Kawase, K. Murakami, S. F. Chen, Y. Li, B. Calagui, L. Reola, E. Carlson, and C. J. Epstein
Overexpression of SOD1 in Transgenic Rats Protects Vulnerable Neurons Against Ischemic Damage After Global Cerebral Ischemia and Reperfusion
J. Neurosci.,
October 15, 1998;
18(20):
8292 - 8299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-H. Jo, M.-K. Son, H.-J. Koh, S.-M. Lee, I.-H. Song, Y.-O. Kim, Y.-S. Lee, K.-S. Jeong, W. B. Kim, J.-W. Park, et al.
Control of Mitochondrial Redox Balance and Cellular Defense against Oxidative Damage by Mitochondrial NADP+-dependent Isocitrate Dehydrogenase
J. Biol. Chem.,
May 4, 2001;
276(19):
16168 - 16176.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kiryu-Seo, M. Sasaki, H. Yokohama, S. Nakagomi, T. Hirayama, S. Aoki, K. Wada, and H. Kiyama
Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers
PNAS,
April 11, 2000;
97(8):
4345 - 4350.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
