The mechanism of apolipoprotein B-100 thiol depletion during oxidative modification of low-density lipoprotein

Eric Ferguson, Ravinder Jit Singh, Neil Hogg, B. Kalyanaraman

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Abstract

Oxidation of low-density lipoprotein (LDL) is recognized to be a key step in atherogenesis. Previous studies show that LDL contains low-molecular- weight antioxidants such as vitamin E, β-carotene, and ubiquinol, which can retard oxidative modification. In this report, we have evaluated the antioxidant potential of apolipoprotein B-100 (apo-B) thiols during LDL oxidation. Bath apo-B thiols and vitamin E were depleted concomitantly during the lag phase of Cu2+ -mediated LDL oxidation. The rate of thiol depletion was significantly inhibited by the lipophilic spin trap N-tert-butyl-α- phenylnitrone (PBN) but not by the water-soluble spin trap α-(4-pyridyl-1- oxide)-N-tert-butylnitrone (POBN). Blocking apo-B thiols with sulfhydryl modifying agents increased the oxidizability of LDL. As with Cu2+, peroxynitrite also caused depletion of apoB thiols, and again thiol depletion was inhibited by PBN but not by POBN. A PBN/lipid-derived radical adduct was observed by the electron spin resonance technique during oxidation of LDL with peroxynitrite. We conclude that apo-B thiol depletion is mediated by lipid peroxidation, prior to the onset of the propagation phase of LDL oxidation. The implications of apoB thiols as intrinsic antioxidants of LDL are discussed.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume341
Issue number2
DOIs
StatePublished - May 15 1997

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Keywords

  • electron spin resonance
  • lipid peroxidation
  • low-density lipoprotein
  • peroxynitrite
  • protein thiols

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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