Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation

Noriyuki Shibata, Asao Hirano, E. Tessa Hedley-Whyte, Mauro C. Dal Canto, Ryoji Nagai, Koji Uchida, Seikoh Horiuchi, Motoko Kawaguchi, Tomoko Yamamoto, Makio Kobayashi

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Recent studies have documented carbonyl stress involvement in the pathogenesis of sporadic amyotrophic lateral sclerosis (ALS). The aim of the present study was to assess a role for carbonyl stress in motor neuron degeneration associated with superoxide dismutase-1 (SOD1) mutant familial ALS and its transgenic mouse model, using an immunohistochemical investigation of advanced glycation end products (AGEs) and advanced lipoxidation end products (ALEs). In the spinal cords from six familial ALS patients with SOD1 A4V mutation and six transgenic mice expressing G93A mutant human SOD1, immunoreactivities for Nε-(carboxyethyl)lysine, argpyrimidine, pyrraline and Nε-(carboxymethyl)lysine as AGEs were distinct in almost all of the reactive astrocytes and obscure in the residual neurons, whereas no immunoreactivity for pentosidine as an AGE, or 4-hydroxy-2-nonenalhistidine, malondialdehyde-lysine or acrolein-lysine as ALEs was detectable. Spinal cords from age-matched control humans and mice exhibited no significant immunoreactivities for the examined products. Our results indicate that protein glycation, but not lipid peroxidation, is enhanced in ALS patients with an SOD1 mutation and mutant SOD1 transgenic mice, in which certain AGEs are selectively formed in the spinal cord astrocytes.

Original languageEnglish (US)
Pages (from-to)171-178
Number of pages8
JournalActa neuropathologica
Volume104
Issue number2
DOIs
StatePublished - Dec 1 2002

Keywords

  • Advanced glycation end products
  • Amyotrophic lateral scalerosis
  • Astrocyte
  • Superoxide dismutase
  • Transgenic mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Shibata, N., Hirano, A., Hedley-Whyte, E. T., Dal Canto, M. C., Nagai, R., Uchida, K., Horiuchi, S., Kawaguchi, M., Yamamoto, T., & Kobayashi, M. (2002). Selective formation of certain advanced glycation end products in spinal cord astrocytes of humans and mice with superoxide dismutase-1 mutation. Acta neuropathologica, 104(2), 171-178. https://doi.org/10.1007/s00401-002-0537-5