title: Immunochemical detection of a lipofuscin-like fluorophore derived from malondialdehyde and lysine.
abstract: The accumulation of fluorescent age pigment or lipofuscin is a frequently observed age-associated cellular alteration in a variety of postmitotic cells of many species. These pigments are observed within granules composed, in part, of damaged protein and lipid. Modification of various biomolecules by aldehyde products of lipid peroxidation is believed to contribute to lipofuscin and ceroid formation. In the present study, we raised a monoclonal antibody (MAb 1F83) directed to the malondialdehyde-modified protein and identified a lipofuscin-like dihydropyridine fluorophore as the major epitope. This antibody was used to conclusively demonstrate that the fluorophore forms on oxidatively modified low density lipoproteins. In addition, we demonstrated that the materials immunoreactive to MAb 1F83 indeed constituted the atherosclerotic lesions, in which intense positivity was associated primarily with macrophage-derived foam cells. The results of this study suggest that the reaction between the lipid peroxidation-derived aldehyde and primary amino groups of protein might represent a process common to the formation of the lipofuscin-like fluorophore during aging and its related diseases.
authors.affiliation: Tsukuba Research Laboratory, NOF Company, Tsukuba 300-2635, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Kumazawa
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Itakura
authors.forename: N
authors.initials: N
authors.lastname: Shibata
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: T
authors.initials: T
authors.lastname: Osawa
authors.forename: K
authors.initials: K
authors.lastname: Uchida
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000378:metabolism; D003300:Copper / Q000737:chemistry; D004095:Dihydropyridines / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis* / Q000737:chemistry*; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000737:chemistry; D015227:Lipid Peroxidation; D008062:Lipofuscin / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry; D008239:Lysine / Q000737:chemistry*; D008315:Malondialdehyde / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004095:Dihydropyridines; D000939:Epitopes; D005456:Fluorescent Dyes; D007328:Insulin; D008062:Lipofuscin; D008077:Lipoproteins, LDL; D012710:Serum Albumin, Bovine; D008315:Malondialdehyde; D003300:Copper; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D008239:Lysine