Neuroprotective effects of an antioxidant in cortical cerebral ischemia: prevention of early reduction of the apurinic/apyrimidinic endonuclease DNA repair enzyme

被引:19
作者
Chang, YY
Fujimura, M
Morita-Fujimura, Y
Kim, GW
Huang, CY
Wu, HS
Kawase, M
Copin, JC
Chan, PH
机构
[1] Stanford Univ, Sch Med, Dept Neurosurg, Palo Alto, CA 94304 USA
[2] Stanford Univ, Sch Med, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA
[3] Stanford Univ, Sch Med, Program Neurosci, Palo Alto, CA 94304 USA
关键词
photothiombotic cortical cerebral ischemia; apurinic/apyrimidinic endonuclease; DNA base excision repair; reactive oxygen species; free radical scavenger;
D O I
10.1016/S0304-3940(99)00799-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We examined the effects of the free radical scavenger, 21-aminosteroid, on apurinic/apyrimidinic endonuclease (APE/Ref-1) protein expression and subsequent infarction volume after photothrombotic cortical cerebral ischemia in mice. Immunohistochemistry and Western blot analysis showed a significant reduction in APE/Ref-1 expression 6 and 24 h after ischemia in untreated animals, whereas in drug-treated animals the reduction was much less at the same time points. The administration of 21-aminosteroid significantly decreased subsequent infarction volume 3 days after ischemia. These data suggest that 21-aminosteroid prevents the early decrease of APE/Ref-1 expression, thereby reducing cortical infarction after photothrombotic cerebral ischemia. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:61 / 64
页数:4
相关论文
共 11 条
[1]   Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway [J].
Bennett, RAO ;
Wilson, DM ;
Wong, D ;
Demple, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (14) :7166-7169
[2]   Role of oxidants in ischemic brain damage [J].
Chan, PH .
STROKE, 1996, 27 (06) :1124-1129
[3]  
DEMPLE B, 1994, ANNU REV BIOCHEM, V63, P915, DOI 10.1146/annurev.biochem.63.1.915
[4]   Early decrease of apurinic/apyrimidinic endonuclease expression after transient focal cerebral ischemia in mice [J].
Fujimura, M ;
Morita-Fujimura, Y ;
Kawase, M ;
Chan, PH .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1999, 19 (05) :495-501
[5]  
Hall E D, 1994, Adv Pharmacol, V28, P221, DOI 10.1016/S1054-3589(08)60497-4
[6]   Reduction of apurinic/apyrimnidinic endonuclease expression after transient global cerebral ischemia in rats - Implication of the failure of DNA repair in neuronal apoptosis [J].
Kawase, M ;
Fujimura, M ;
Morita-Fujimura, Y ;
Chan, PH .
STROKE, 1999, 30 (02) :441-448
[7]   MUTAGENESIS BY APURINIC APYRIMIDINIC SITES [J].
LOEB, LA ;
PRESTON, BD .
ANNUAL REVIEW OF GENETICS, 1986, 20 :201-230
[8]   Early decrease in apurinic/apyrimidinic endonuclease is followed by DNA fragmentation after cold injury-induced brain trauma in mice [J].
Morita-Fujimura, Y ;
Fujimura, M ;
Kawase, M ;
Chan, PH .
NEUROSCIENCE, 1999, 93 (04) :1465-1473
[9]   Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals [J].
Ramana, CV ;
Boldogh, I ;
Izumi, T ;
Mitra, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (09) :5061-5066
[10]  
Robertson KA, 1997, CELL GROWTH DIFFER, V8, P443