Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.
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.
Abe
Shinji
S
Department of Clinical Pharmacy, Tokushima University Hospital, Japan.
Ohnishi
Hideki
H
Tsuchiya
Koichiro
K
Ishizawa
Keisuke
K
Torii
Mayumi
M
Kanematsu
Yasuhisa
Y
Kawazoe
Kazuyoshi
K
Minakuchi
Kazuo
K
Yoshizumi
Masanori
M
Tamaki
Toshiaki
T
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*
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