Protective effects of extracellular glutathione against Zn2+-induced cell death in vitro and in vivo
Article first published online: 13 OCT 2003
Copyright © 2003 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 74, Issue 5, pages 736–743, 1 December 2003
How to Cite
Cho, I. H., Im, J.-Y., Kim, D., Kim, K.-S., Lee, J.-K. and Han, P.-L. (2003), Protective effects of extracellular glutathione against Zn2+-induced cell death in vitro and in vivo. J. Neurosci. Res., 74: 736–743. doi: 10.1002/jnr.10794
- Issue published online: 17 NOV 2003
- Article first published online: 13 OCT 2003
- Manuscript Accepted: 21 JUL 2003
- Manuscript Revised: 11 JUL 2003
- Manuscript Received: 25 APR 2003
- Ministry of Health & Welfare, Republic of Korea. Grant Number: 02-PJ1-PG3-21304-0011
- Zn2+ toxicity;
- kainic acid;
The central nervous system reserves high concentrations of free Zn2+ in certain excitatory synaptic vesicles. In pathological conditions such as transient cerebral ischemia, traumatic brain injury, and kainic acid (KA)-induced seizure, free Zn2+ is released in excess at synapses, which causes neuronal and glial death. We report here that glutathione (GSH) can be used as an effective means for protection of neural cells from Zn2+-induced cell death in vitro and in vivo. Chronic treatment with 35 μM Zn2+ led to death of primary cortical neurons and primary astrocytes. The Zn2+ toxicity of cortical neurons was partially protected by 1 mM of GSH, whereas the Zn2+ toxicity of primary astrocyte cultures was blocked completely by 100 μM of GSH. To evaluate the beneficial effects of GSH in vivo, an excitotoxin-induced neural cell death model was established by intracerebroventricular (i.c.v.) injection of 0.94 nmol (0.2 μg) KA, which produced selective neuronal death, especially in CA1 and CA3 hippocampal regions. The i.c.v. co-injection of 200 pmol of GSH significantly attenuated KA-induced neuronal cell death and reactive gliosis in hippocampus. The results of this study suggest the contribution of Zn2+ in the excitotoxin-induced neural cell death model and a potential value of GSH as a therapeutic means against Zn2+-induced pathogenesis in brain. © 2003 Wiley-Liss, Inc.