title: Disparate roles of zinc in chemical hypoxia-induced neuronal death.
abstract: Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: Sujeong
authors: S
authors: Kim
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: Jung-Woo
authors: JW
authors: Seo
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: Shin Bi
authors: SB
authors: Oh
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: So Hee
authors: SH
authors: Kim
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: Inki
authors: I
authors: Kim
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea.
authors: Nayoung
authors: N
authors: Suh
authors: Asan Institute for Life Sciences, Asan Medical Center, Seoul South Korea ; Department of Neurology, University of Ulsan College of Medicine, Seoul South Korea.
authors: Joo-Yong
authors: JY
authors: Lee
keywords: brain injury; delayed neuronal death; iron; metal chelation; neuroprotection