title: Expression of zinc transporter gene, ZnT-1, is induced after transient forebrain ischemia in the gerbil.
abstract: 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.
authors.affiliation: Department of Molecular Neurobiology (TANABE), Osaka University Medical School, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
authors.forename: K
authors.initials: K
authors.lastname: Imaizumi
authors.forename: T
authors.initials: T
authors.lastname: Katayama
authors.forename: K
authors.initials: K
authors.lastname: Kitagawa
authors.forename: A
authors.initials: A
authors.lastname: Wanaka
authors.forename: M
authors.initials: M
authors.lastname: Tohyama
authors.forename: T
authors.initials: T
authors.lastname: Takagi
mesh_terms: 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
chemical_list: D027682:Cation Transport Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D012333:RNA, Messenger; C092392:Slc30a1 protein, rat; D015032:Zinc