Cadmium-induced astroglial death proceeds via glutathione depletion
Article first published online: 29 DEC 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 83, Issue 2, pages 301–308, 1 February 2006
How to Cite
Im, J.-Y., Paik, S.-G. and Han, P.-L. (2006), Cadmium-induced astroglial death proceeds via glutathione depletion. J. Neurosci. Res., 83: 301–308. doi: 10.1002/jnr.20722
- Issue published online: 17 JAN 2006
- Article first published online: 29 DEC 2005
- Manuscript Accepted: 17 OCT 2005
- Manuscript Revised: 20 SEP 2005
- Manuscript Received: 16 JUL 2005
- Brain Research Center
- The 21st Century Frontier Research Program of the Ministry of Science and Technology, Republic of Korea. Grant Number: M103KV010020 03K2201 02020
- thiol-containing compounds
Cadmium is a heavy metal that accumulates in the body, and its accumulation in the brain damages both neurons and glial cells. In the current study, we explored the mechanism underlying cadmium toxicity in primary cortical astroglia cultures. Chronic treatment with 10 μM cadmium was sufficient to cause 90% cell death in 18 hr. However, unlike that observed in neurons, cadmium-induced astroglial toxicity was not attenuated by the antioxidants trolox (100 μM), caffeic acid (1 mM), and vitamin C (1 mM). In contrast, extracellular 100 μM glutathione (GSH; γ-Glu-Cys-Gly) or 100 μM cysteine almost completely blocked cadmium-induced astroglial death, whereas 300 μM oxidized GSH (GSSG) or 300 μM cystine, which do not have the free thiol group, were ineffective. In addition, cadmium toxicity was noticeably inhibited or enhanced when intracellular GSH was, respectively, increased by using the cell-permeable glutathione ethyl ester (GSH-EE) or depleted by using buthionine sulfoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase. In agreement with these data, intracellular GSH levels were found to be depressed in cadmium-treated astrocytes. These results suggest that the toxic effect of cadmium on primary astroglial cells involves GSH depletion and, furthermore, that GSH administration can potentially be used to counteract cadmium-induced astroglial cell death therapeutically. © 2005 Wiley-Liss, Inc.