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

39 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Apolipoprotein B-100
LDL Lipoproteins
Phospholipases A2
Hydrolysis
Phospholipids
Proteins
Plasmas
Secretory Phospholipase A2
Nitration
Amyloidogenic Proteins
oxidized low density lipoprotein
Electrophoretic mobility
Snake Venoms
Peroxynitrous Acid
Circular Dichroism
Unsaturated Fatty Acids
Oligomers
Amyloid
Lipid Peroxidation
Copper

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein. / Asatryan, Liana; Hamilton, Ryan T.; Isas, J. Mario; Hwang, Juliana; Kayed, Rakez; Sevanian, Alex.

In: Journal of Lipid Research, Vol. 46, No. 1, 01.2005, p. 115-122.

Research output: Contribution to journalArticle

Asatryan, Liana ; Hamilton, Ryan T. ; Isas, J. Mario ; Hwang, Juliana ; Kayed, Rakez ; Sevanian, Alex. / LDL phospholipid hydrolysis produces modified electronegative particles with an unfolded apoB-100 protein. In: Journal of Lipid Research. 2005 ; Vol. 46, No. 1. pp. 115-122.
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