LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein

Liana Asatryan, Ryan T. Hamilton, J. Mario Isas, Juliana Hwang, Rakez Kayed, Alex Sevanian

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Electronegative low density lipoprotein (LDL-) formation that structurally resembles LDL- isolated from plasma was evaluated after LDL treatment with snake venom phospholipase A2 (PLA2). PLA2 treatment of LDL increased its electrophoretic mobility in proportion to the amount of LDL- formed without evidence of lipid peroxidation. These changes dose-dependently correlated with the degree of phospholipid hydrolysis. Strong immunoreactivity of LDL- subfraction from plasma and PLA2-treated LDL (PLA2-LDL) to amyloid oligomer-specific antibody was observed. Higher β-strand structural content and unfolding proportionate to the loss of α-helical structure of apolipoprotein B-100 (apoB-100) of LDL- isolated from both native and PLA2-LDLs was demonstrated by circular dichroism (CD) spectropolarimetry. These structural changes resembled the characteristics of some oxidatively modified LDLs and soluble oligomeric aggregates of amyloidogenic proteins. PLA2-LDL was also more susceptible to nitration by peroxynitrite, likely because of exposure of otherwise inaccessible hydrophilic and hydrophobic domains arising from apoB-100 unfolding. This was also demonstrated for plasma LDL-. In contrast, PLA2-LDL was more resistant to copper-mediated oxidation that was reversed upon the addition of small amounts of unsaturated fatty acids. The observed similarities between PLA2-LDL--derived LDL- and plasma LDL- implicate a role for secretory PLA2 in producing modified LDL- that is facilitated by unfolding of apoB-100.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalJournal of Lipid Research
Volume46
Issue number1
DOIs
StatePublished - Jan 2005

Keywords

  • Apolipoprotein B-100
  • Atherogenic low density lipoprotein
  • Lipid peroxidation
  • Nitrotyrosine
  • Oxidation
  • Protein structure
  • Secretory phospholipase A
  • Unsaturated fatty acids
  • β-strand structures

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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