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

Noriyuki Shibata, Satoshi Yamada, Koji Uchida, Asao Hirano, Saburo Sakoda, Harutoshi Fujimura, Shoichi Sasaki, Makoto Iwata, Sono Toi, Motoko Kawaguchi, Tomoko Yamamoto, Makio Kobayashi

Research output: Contribution to journalArticle

32 Scopus citations

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 IgG1 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.

Original languageEnglish (US)
Pages (from-to)170-177
Number of pages8
JournalBrain research
Volume1019
Issue number1-2
DOIs
StatePublished - Sep 3 2004

Keywords

  • 4-Hydroxy-2-hexenal
  • 4-Hydroxyalkenal
  • Amyotrophic lateral sclerosis
  • Lipid peroxidation
  • Oxidative stress
  • Polyunsaturated fatty acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Shibata, N., Yamada, S., Uchida, K., Hirano, A., Sakoda, S., Fujimura, H., Sasaki, S., Iwata, M., Toi, S., Kawaguchi, M., Yamamoto, T., & Kobayashi, M. (2004). Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis. Brain research, 1019(1-2), 170-177. https://doi.org/10.1016/j.brainres.2004.05.110