Effects of recombinant superoxide dismutase on manganese superoxide dismutase gene expression in gerbil hippocampus after ischemia.
OBJECTIVE
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 (8 x 10(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.
Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
T
T
Matsuyama
S
S
Shimizu
H
H
Nakamura
H
H
Michishita
M
M
Tagaya
M
M
Sugita
D000595:Amino Acid Sequence; D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology*; D016923:Cell Death; D015870:Gene Expression / Q000187:drug effects*; D005849:Gerbillinae; D006624:Hippocampus / Q000201:enzymology* / Q000473:pathology*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*
D012333:RNA, Messenger; D013482:Superoxide Dismutase