Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: involvement of heat-shock proteins and Bcl-2
Article first published online: 7 JUL 2008
Journal of Neurochemistry
Volume 79, Issue 2, pages 361–370, October 2001
How to Cite
Guo, Z., Lee, J., Lane, M. and Mattson, M. P. (2001), Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: involvement of heat-shock proteins and Bcl-2. Journal of Neurochemistry, 79: 361–370. doi: 10.1046/j.1471-4159.2001.00564.x
- Issue published online: 7 JUL 2008
- Article first published online: 7 JUL 2008
- Received April 27, 2001; revised manuscript received August 3, 2001; accepted August 3, 2001.
- cerebral ischemia;
- heat-shock proteins 70 and 90;
- membrane lipid peroxidation;
- mitochondrial transmembrane potential.
Mild metabolic stress may increase resistance of neurons in the brain to subsequent, more severe insults, as demonstrated by the ability of ischemic pre-conditioning and dietary restriction to protect neurons in experimental models of stroke- and age-related neurodegenerative disorders. In the present study we employed iodoacetic acid (IAA), an inhibitor of glyceraldehyde-3-phosphate dehydrogenase, to test the hypothesis that inhibition of glycolysis can protect neurons. Pre-treatment of cultured hippocampal neurons with IAA can protect them against cell death induced by glutamate, iron and trophic factor withdrawal. Surprisingly, protection occurred with concentrations of IAA (2–200 nm) much lower than those required to inhibit glycolysis. Pre-treatment with IAA results in suppression of oxyradical production and stabilization of mitochondrial function in neurons after exposure to oxidative insults. Levels of the stress heat-shock proteins HSP70 and HSP90, and of the anti-apoptotic protein Bcl-2, were increased in neurons exposed to IAA. Our data demonstrate that IAA can stimulate cytoprotective mechanisms within neurons, and suggest the possible use of IAA and related compounds in the prevention and/or treatment of neurodegenerative conditions.