Mice Overexpressing 70-kDa Heat Shock Protein Show Increased Resistance to Malonate and 3-Nitropropionic Acid

Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia–ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing m...

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Bibliographic Details
Published in:Experimental neurology 2002-07, Vol.176 (1), p.262-265
Main Authors: Dedeoglu, Alpaslan, Ferrante, Robert J., Andreassen, Ole A., Dillmann, Wolfgang H., Beal, M.Flint
Format: Article
Language:English
Subjects:
3-NP
Animals
Biological and medical sciences
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Corpus Striatum - pathology
Cytoprotection - genetics
Cytoprotection - physiology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Drug Resistance - genetics
Female
Heterozygote
Homozygote
HSP-70
HSP70 Heat-Shock Proteins - biosynthesis
HSP70 Heat-Shock Proteins - genetics
HSP70 Heat-Shock Proteins - physiology
Huntington's disease
Male
malonate
Malonates - pharmacology
Medical sciences
Mice
Mice, Transgenic
Neurology
Neuropharmacology
Neuroprotective agent
Nitro Compounds
Pharmacology. Drug treatments
Propionates - pharmacology
Succinate Dehydrogenase - antagonists & inhibitors
Transgenes
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Summary:Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia–ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing mitochondrial dysfunction, which triggers the generation of superoxide radicals, secondary excitotoxicity, and apoptosis. In this study, we examined whether the 70-kDa heat shock protein (HSP-70) is protective against neurotoxicity induced by malonate and 3-NP. Homozygous and heterozygous HSP-70 overexpressing mice (HSP-70+/+, HSP-70+/−) and wild-type controls received 3-NP or malonate and striatal lesion sizes were evaluated by stereology. Compared to HSP-70+/+ and HSP-70+/−, wild-type controls showed significantly larger striatal lesions following 3-NP or malonate injections. These findings support the idea that HSP-70 has a neuroprotective role that may be useful in the treatment of neurodegenerative diseases.
ISSN:0014-4886
1090-2430
DOI:10.1006/exnr.2002.7933