Expression of zinc transporter gene, ZnT-1, is induced after transient forebrain ischemia in the gerbil.
To elucidate the molecular mechanisms underlying neuronal death after transient forebrain ischemia, we cloned genes expressed after transient forebrain ischemia in the Mongolian gerbil by a differential display method. A gerbil homolog of rat zinc transporter, ZnT-1, which transports intracellular Zn2+ out of cells, was isolated. Its expression became detectable exclusively in pyramidal neurons of the CA1 region 12 hr after ischemia and reached a maximum from day 1 to day 2 as shown by in situ hybridization. By day 7, expression had disappeared entirely from the cells in the CA1 region, because the neurons had died. No other brain regions exhibited such a significant level of ZnT-1 mRNA expression during this period. Zn2+ was shown to accumulate in CA1 pyramidal neurons expressing ZnT-1 mRNA after the ischemia by using zinquin, a zinc-specific fluorescent dye. When primary hippocampal neurons were exposed to a high dose of Zn2+, ZnT-1 mRNA accumulated. These results suggest that the induction of ZnT-1 mRNA observed in CA1 neurons was caused by an increase in the intracellular Zn2+ concentration. It was reported recently that Zn2+ chelator blocked neuronal death after ischemia and that the influx of Zn2+ might be a key mechanism underlying neuronal death. The induction of ZnT-1 mRNA in CA1 pyramidal neurons fated to die after transient ischemia is of interest to the study of postischemic events and the molecular mechanisms underlying delayed neuronal death.
Tsuda
M
M
Department of Molecular Neurobiology (TANABE), Osaka University Medical School, Osaka, Japan.
Imaizumi
K
K
Katayama
T
T
Kitagawa
K
K
Wanaka
A
A
Tohyama
M
M
Takagi
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004351:Drug Resistance; D005786:Gene Expression Regulation; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D016548:Prosencephalon / Q000098:blood supply*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology
D027682:Cation Transport Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; C092392:Slc30a1 protein, rat; D015032:Zinc