Protein and DNA oxidation in spinal injury: Neurofilaments - An oxidation target

Michael L. Leski, Feng Bao, Liqin Wu, Hao Qian, Dachuan Sun, Danxia Liu

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

This study measured the time courses of protein and DNA oxidation following spinal cord injury (SCI) in rats and characterized oxidative degradation of proteins. Protein carbonyl content - a marker of protein oxidation - significantly increased at 3-9 h postinjury and the ratio 8-hydroxy-2-deoxyguanosine/deoxyguanosine - an indicator of DNA oxidation - was significantly higher at 3-6 h postinjury in the injured cords than in the sham controls. This suggests that oxidative modification of proteins and DNA contributes to secondary damage in SCI. Densities of selected bands on coomassie-stained gels indicated that most proteins were degraded. Neurofilament protein (NFP) was particularly evaluated immunohistochemically; its light chain (NFP-68) was gradually degraded in nerve fibers, neuron bodies, and large dendrites following SCI. A mixture of Mn (III) tetrakis (4-benzoic acid) porphyrin (10 mg/kg) - a novel SOD mimetic - and nitro-L-arginine (1 mg/kg) - an inhibitor of nitric oxide synthase - injected intraperitoneally, increased NFP-68 immunoreactivity and the numbers of NFP-positive nerve fibers post-SCI, correlating NFP degradation in SCI to free radical-triggered oxidative damage for the first time. Therefore, blockage of protein and DNA oxidation in the secondary injury stage may improve long-term recovery - important information for development of the SCI therapies.

Original languageEnglish (US)
Pages (from-to)613-624
Number of pages12
JournalFree Radical Biology and Medicine
Volume30
Issue number6
DOIs
StatePublished - Mar 15 2001

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Keywords

  • 8-hydroxy-2-deoxyguanosine
  • DNA oxidation
  • Free radicals
  • HPLC analysis
  • Immunohistochemical staining
  • Mn (III) tetrakis (4-benzoic acid) porphyrin
  • Neurofilament
  • Nitro-L-arginine
  • Protein carbonyl content
  • Protein degradation
  • Protein oxidation
  • Spinal cord injury

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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