4-Hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake

Joe E. Springer, Robert D. Azbill, Robert J. Mark, James G. Begley, Georg Waeg, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Traumatic injury to the spinal cord initiates a host of pathophysiological events that are secondary to the initial insult. One such event is the accumulation of free radicals that damage lipids, proteins, and nucleic acids. A major reactive product formed following lipid peroxidation is the aldehyde, 4-hydroxynonenal (HNE), which cross-links to side chain amino acids and inhibits the function of several key metabolic enzymes. In the present study, we used immunocytochemical and immunoblotting techniques to examine the accumulation of protein-bound HNE, and synaptosomal preparations to study the effects of spinal cord injury and HNE formation on glutamate uptake. Protein-bound HNE increased in content in the damaged spinal cord at early times following injury (1-24 h) and was found to accumulate in myelinated fibers distant to the site of injury. Immunoblots revealed that protein-bound HNE levels increased dramatically over the same postinjury interval. Glutamate uptake in synaptosomal preparations from injured spinal cords was decreased by 65% at 24 h following injury. Treatment of control spinal cord synaptosomes with HNE was found to decrease significantly, in a dose-dependent fashion, glutamate uptake, an effect that was mimicked by inducers of lipid peroxidation. Taken together, these findings demonstrate that the lipid peroxidation product HNE rapidly accumulates in the spinal cord following injury and that a major consequence of HNE accumulation is a decrease in glutamate uptake, which may potentiate neuronal cell dysfunction and death through excitotoxic mechanisms.

Original languageEnglish (US)
Pages (from-to)2469-2476
Number of pages8
JournalJournal of Neurochemistry
Volume68
Issue number6
StatePublished - Jun 1997
Externally publishedYes

Keywords

  • Excitotoxic neuronal cell death
  • Free radicals
  • Glutamate transporter
  • Lipid peroxidation
  • Spinal cord injury

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Springer, J. E., Azbill, R. D., Mark, R. J., Begley, J. G., Waeg, G., & Mattson, M. P. (1997). 4-Hydroxynonenal, a lipid peroxidation product, rapidly accumulates following traumatic spinal cord injury and inhibits glutamate uptake. Journal of Neurochemistry, 68(6), 2469-2476.