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Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids.

Authors
  • Jolivalt, C
  • Leininger-Muller, B
  • Bertrand, P
  • Herber, R
  • Christen, Y
  • Siest, G
Type
Published Article
Journal
Free Radical Biology and Medicine
Publisher
Elsevier
Publication Date
Jan 01, 2000
Volume
28
Issue
1
Pages
129–140
Identifiers
PMID: 10656299
Source
Medline
License
Unknown

Abstract

Accumulation of oxidized proteins has been demonstrated in the brain of patients suffering from Alzheimer's disease (AD). Among the proteins found in cerebral amyloid deposits, apolipoprotein (apo) E is a polymorphic protein which one specific isoform, apo E4, has been widely associated with AD. Apo E may be linked with AD by its isoform-specific interaction with lipids or other proteins in amyloid plaques. Using the myeloperoxidase oxidative system, we report that oxidation of the three recombinant apo E isoforms is differential (as estimated using immunoblot and high-performance liquid chromatography analysis), with apo E4 being more susceptible than apo E3, which in turn is much more susceptible than apo E2. In addition, susceptibility to thrombin proteolysis is reduced when apo E is oxidized, and oxidation of apo E decreases its incorporation into phospholipid discs by approximately 50%. Oxidation of apo E may contribute to inefficient lipid recycling in the brain, particularly regarding apo E4 and E3. Our results link and strengthen both the E4 allele linkage with AD and the role of protein oxidation in AD. The cerebral mechanisms underlying apo E oxidation and/or myeloperoxidase functions in vivo remain to be assessed.

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