Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury: Involvement of heat-shock proteins and Bcl-2

Zhihong Guo, Jaewon Lee, Mark Lane, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)361-370
Number of pages10
JournalJournal of Neurochemistry
Volume79
Issue number2
DOIs
StatePublished - 2001

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Iodoacetic Acid
Iodoacetates
Heat-Shock Proteins
Neurons
Wounds and Injuries
Glycolysis
HSP90 Heat-Shock Proteins
Ischemic Preconditioning
Apoptosis Regulatory Proteins
Physiological Stress
Glyceraldehyde-3-Phosphate Dehydrogenases
HSP70 Heat-Shock Proteins
Cell death
Neurodegenerative Diseases
Glutamic Acid
Brain
Cell Death
Theoretical Models
Therapeutics
Iron

Keywords

  • Apoptosis
  • Cerebral ischemia
  • Glutamate
  • Heat-shock proteins 70 and 90
  • Membrane lipid peroxidation
  • Mitochondrial transmembrane potential

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury : Involvement of heat-shock proteins and Bcl-2. / Guo, Zhihong; Lee, Jaewon; Lane, Mark; Mattson, Mark P.

In: Journal of Neurochemistry, Vol. 79, No. 2, 2001, p. 361-370.

Research output: Contribution to journalArticle

Guo, Zhihong ; Lee, Jaewon ; Lane, Mark ; Mattson, Mark P. / Iodoacetate protects hippocampal neurons against excitotoxic and oxidative injury : Involvement of heat-shock proteins and Bcl-2. In: Journal of Neurochemistry. 2001 ; Vol. 79, No. 2. pp. 361-370.
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