Article

Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis.

Department of Pathology, Tokyo Women's Medical University, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162-8666, Japan.
Brain Research (impact factor: 2.73). 10/2004; 1019(1-2):170-7. DOI:10.1016/j.brainres.2004.05.110
Source: PubMed

ABSTRACT 4-Hydroxy-2-hexenal (HHE) is a toxic, reactive aldehydic intermediate formed by nonenzymatic peroxidation of n-3 polyunsaturated fatty acids. The aim of this study was to determine the implication for HHE in the pathomechanism of amyotrophic lateral sclerosis (ALS) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) techniques using a mouse monoclonal IgG(1) antibody mAbHHE53 specific for protein-bound HHE. Immunohistochemical analysis on formalin-fixed, paraffin-embedded sections and frozen sections of spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects demonstrated that protein-bound HHE immunoreactivity was seen and was prominent in the entire gray matter in the ALS cases and localized in the neurons, reactive astrocytes, microglial cells, and the surrounding neuropil, while the immunoreactivity was obscure or undetectable in the control cases. No significant protein-bound HHE immunoreactivity was seen in sections processed with omission of mAbHHE53 or in sections incubated with the antibody with an excess of the respective antigen. Competitive ELISA analysis on trypsin-digested protein extracts of fresh-frozen spinal cord samples disclosed a significant increase in protein-bound HHE level in the ALS cases compared with the control cases. Our results indicate that enhanced HHE formation occurs in the entire gray matter of sporadic ALS spinal cords and suggest that the selective vulnerability of motor neurons to HHE mediates the pathomechanism of this disease.

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Keywords

10 age-matched control subjects
 
amyotrophic lateral sclerosis
 
Competitive ELISA analysis
 
enhanced HHE formation
 
entire gray matter
 
enzyme-linked immunosorbent assay
 
fresh-frozen spinal cord samples
 
Immunohistochemical analysis
 
microglial cells
 
mouse monoclonal IgG(1)
 
n-3 polyunsaturated fatty acids
 
nonenzymatic peroxidation
 
paraffin-embedded sections
 
reactive aldehydic intermediate
 
reactive astrocytes
 
sections incubated
 
selective vulnerability
 
spinal cords
 
sporadic ALS spinal cords
 
surrounding neuropil