Characterisation of adducts of the lipid peroxidation product 4-hydroxy-2-nonenal and amyloid beta-peptides by liquid chromatography/electrospray ionisation mass spectrometry.
Alzheimer's disease is characterised by brain neuritic plaques composed of a 39-44 amino acid peptide (Abeta). Lipid peroxidation is an early event induced by these amyloid beta-peptides, leading to the formation of 4-hydroxy-2-nonenal (HNE), which is one of the major end products of this process. HNE has been reported to form adducts via a stable covalent binding to proteins through a Michael addition to amino acid residues with a nucleophilic side chain. The present study reports an investigation of the conditions for formation of Abeta-HNE (Abeta 1-28 and Abeta 1-42) adducts, and their characterisation by liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS). The results suggest that one or more HNE moieties are localised in the 6-16 region of these adducts, while Asp-1, Lys-16 and Lys-28 are not modified under the described reaction conditions.
Magni
F
F
Mass Spectrometry Unit, IRCCS San Raffaele, Milan, Italy. magni.fulvio@hsr.it
Galbusera
C
C
Tremolada
L
L
Ferrarese
C
C
Kienle
M Galli
MG
D000447:Aldehydes / Q000032:analysis*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000032:analysis*; D002853:Chromatography, Liquid; D006868:Hydrolysis; D015227:Lipid Peroxidation; D008969:Molecular Sequence Data; D021241:Spectrometry, Mass, Electrospray Ionization; D014357:Trypsin
D000447:Aldehydes; D000596:Amino Acids; D016229:Amyloid beta-Peptides; D014357:Trypsin; C027576:4-hydroxy-2-nonenal