Differential oxidation of apolipoprotein E isoforms and interaction with phospholipids.
|
| 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.
|
|---|---|
| Authors | C Jolivalt, B Leininger-Muller, P Bertrand, R Herber, Y Christen, G Siest |
| Journal | Free radical biology & medicine (Free Radic Biol Med) Vol. 28 Issue 1 Pg. 129-40 (Jan 01 2000) ISSN: 0891-5849 [Print] United States |
| PMID | 10656299 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!