Formation of Nepsilon-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification.
The objectives of this study were to estimate the structure of the lipid hydroperoxide-modified lysine residue and to prove the presence of the adducts in vivo. The reaction of lipid hydroperoxide toward the lysine moiety was investigated employing N-benzoyl-glycyl-L-lysine (Bz-Gly-Lys) as a model compound of Lys residues in protein and 13-hydroperoxyoctadecadienoic acid (13-HPODE) as a model of the lipid hydroperoxides. One of the products, compound X, was isolated from the reaction mixture of 13-HPODE and Bz-Gly-Lys and was then identified as N-benzoyl-glycyl-Nepsilon-(hexanonyl)lysine. To prove the formation of Nepsilon-(hexanonyl)lysine, named HEL, in protein exposed to the lipid hydroperoxide, the antibody to the synthetic hexanonyl protein was prepared and then characterized in detail. Using the anti-HEL antibody, the presence of HEL in the lipid hydroperoxide-modified proteins and oxidized LDL was confirmed. Furthermore, the positive staining by anti-HEL antibody was observed in human atherosclerotic lesions using an immunohistochemical technique. The amide-type adduct may be a useful marker for the lipid hydroperoxide-derived modification of biomolecules.
School of Humanities for Environmental Policy and Technology, Himeji Institute of Technology, Himeji 670-0092, USA. yojikato@hept.himeji-tech.ac.jp
Y
Y
Kato
Y
Y
Mori
Y
Y
Makino
Y
Y
Morimitsu
S
S
Hiroi
T
T
Ishikawa
T
T
Osawa
D006801:Humans; D007150:Immunohistochemistry; D008041:Linoleic Acids / Q000737:chemistry*; D008054:Lipid Peroxides / Q000737:chemistry*; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018384:Oxidative Stress; D011506:Proteins / Q000737:chemistry*
D008041:Linoleic Acids; D008054:Lipid Peroxides; C120589:N(epsilon)-hexanoyllysine; D011506:Proteins; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D008239:Lysine