Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque

S Fu, Michael Jonathan Davies, R Stocker, R T Dean

Research output: Contribution to journalJournal articleResearchpeer-review

230 Citations (Scopus)

Abstract

Oxidative damage might be important in atherogenesis. Oxidized lipids are present at significant concentrations in advanced human plaque, although tissue antioxidants are mostly present at normal concentrations. Indirect evidence of protein modification (notably derivatization of lysine) or oxidation has been obtained by immunochemical methods; the specificities of these antibodies are unclear. Here we present chemical determinations of six protein-bound oxidation products: dopa, o-tyrosine, m-tyrosine, dityrosine, hydroxyleucine and hydroxyvaline, some of which reflect particularly oxy-radical-mediated reaction pathways, which seem to involve mainly the participation of transition- metal ions. We compared the relative abundance of these oxidation products in normal intima, and in human carotid plaque samples with that observed after radiolytically generated hydroxyl radical attack on BSA in vitro. The close similarities in relative abundances in the latter two circumstances indicate that hydroxyl radical damage might occur in plaque. The relatively higher level of dityrosine in plaque than that observed after radiolysis suggests the additional involvement of HOCl-mediated reactions in advanced plaque.

Original languageEnglish
JournalBiochemical Journal
Volume333 ( Pt 3)
Pages (from-to)519-25
Number of pages7
ISSN0264-6021
Publication statusPublished - 1 Aug 1998

Keywords

  • Adult
  • Amino Acids
  • Arteriosclerosis
  • Blood Proteins
  • Dihydroxyphenylalanine
  • Female
  • Humans
  • Hydroxides
  • Hydroxyl Radical
  • Hypochlorous Acid
  • Male
  • Middle Aged
  • Oxidation-Reduction
  • Peroxides
  • Proteins
  • Serum Albumin, Bovine
  • Tunica Intima

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