title: Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.
abstract: The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells.
authors.affiliation: Department of Clinical Pharmacy, Tokushima University Hospital, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Torii
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Kanematsu
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kawazoe
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minakuchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshizumi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tamaki
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes; D002470:Cell Survival / Q000187:drug effects; D003620:Dantrolene / Q000494:pharmacology; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013054:Spectrophotometry, Atomic; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002132:Calcium Radioisotopes; D005456:Fluorescent Dyes; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D003620:Dantrolene; D015032:Zinc; D006690:Bisbenzimidazole; D002118:Calcium; D000111:Acetylcysteine