EFFECTS OF RECOMBINANT SUPEROXIDE-DISMUTASE ON MANGANESE SUPEROXIDE-DISMUTASE GENE-EXPRESSION IN GERBIL HIPPOCAMPUS AFTER ISCHEMIA

被引:25
作者
MATSUYAMA, T
SHIMIZU, S
NAKAMURA, H
MICHISHITA, H
TAGAYA, M
SUGITA, M
机构
[1] Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya
关键词
CEREBRAL ISCHEMIA; SUPEROXIDE DISMUTASE; FREE RADICALS; GERBILS;
D O I
10.1161/01.STR.25.7.1417
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose We reported that recombinant human superoxide dismutase ameliorates delayed neuronal death in the postischemic gerbil hippocampus. Since postischemic induction of copper-zinc superoxide dismutase messenger RNA was abolished by this treatment, oxygen radicals generated on reperfusion may induce the expression of this gene. In the present study we examined whether oxygen radicals also induce the expression of manganese superoxide dismutase messenger RNA in the postischemic brain. Methods We induced transient cerebral ischemia by occluding the bilateral common carotid arteries of gerbils. Recombinant human superoxide dismutase (8x10(5) U/kg) or apo-superoxide dismutase was administered intravenously 1 minute before a 5-minute occlusion of the carotid arteries. We analyzed both copper-zinc and manganese superoxide dismutase RNA by in situ hybridization histochemistry and by Northern and dot blot analyses using radioisotope-labeled oligonucleotide probes. Results Hybridization with the manganese superoxide dismutase messenger RNA occurred at the limit of detection in normal CA1 neurons. We observed striking increases in the labeling of CA1 up to 24 hours after 5 minutes of ischemia. The hybridization occurred anew in glial cells of the CA1 layer during 3 to 7 days. Pretreatment with recombinant human superoxide dismutase had no effect on the postischemic induction of manganese superoxide dismutase messenger RNA, whereas the same treatment significantly attenuated (P<.01) the increase in copper-zinc superoxide dismutase messenger RNA. Conclusions Our results demonstrated temporal postischemic induction of manganese superoxide dismutase messenger RNA. The inducer may not be superoxide radicals but may be other chemical mediators such as cytokines.
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页码:1417 / 1423
页数:7
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