TY - JOUR
T1 - Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury
T2 - Involvement of heat-shock proteins and Bcl-2
AU - Guo, Zhihong
AU - Lee, Jaewon
AU - Lane, Mark
AU - Mattson, Mark P.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cerebral ischemia
KW - Glutamate
KW - Heat-shock proteins 70 and 90
KW - Membrane lipid peroxidation
KW - Mitochondrial transmembrane potential
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UR - http://www.scopus.com/inward/citedby.url?scp=0034781048&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2001.00564.x
DO - 10.1046/j.1471-4159.2001.00564.x
M3 - Article
C2 - 11677264
AN - SCOPUS:0034781048
SN - 0022-3042
VL - 79
SP - 361
EP - 370
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -