title: N(ɛ)-(carboxymethyl)lysine modification of elastin alters its biological properties: implications for the accumulation of abnormal elastic fibers in actinic elastosis.
abstract: Accumulation of degenerated elastic fibers in the sun-exposed skin designated as actinic elastosis is a histological hallmark of photodamaged skin. Previous studies have indicated that the elastic fibers of actinic elastosis interact with lysozyme and are modified by N(ɛ)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGEs). We studied here how CML modification of elastin is involved in the pathogenesis of actinic elastosis. The CML-modified insoluble elastin became resistant to neutrophil elastase digestion, which was reversed by treatment with aminoguanidine, a potent inhibitor of AGE formation. In a temperature-dependent aggregation assay, CML-modified elastin rapidly formed self-aggregates, the size of which was larger than unmodified elastin. The elastic fiber sheets prepared from CML-modified α-elastin showed 3D wider diameter, tortuous appearance, and decreased elasticity on tensile tests. The CML-modified α-elastin, but not unmodified α-elastin, was found to bind to lysozyme in vitro, supporting the immunohistochemical findings that the antibodies for lysozyme and CML reacted simultaneously with the elastic fibers of actinic elastosis and UV-irradiated skin. The glycated elastin is likely to cause the accumulation of abnormally aggregated elastic fibers and unusual interaction with lysozyme in actinic elastosis.
authors.affiliation: Department of Dermatology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan. yoshy@med.kindai.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshinaga
authors.forename: Akira
authors.initials: A
authors.lastname: Kawada
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.forename: Eita
authors.initials: E
authors.lastname: Fujimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Wachi
authors.forename: Satoru
authors.initials: S
authors.lastname: Harumiya
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nagai
authors.forename: Shingo
authors.initials: S
authors.lastname: Tajima
mesh_terms: D000328:Adult; D004547:Elastic Tissue / Q000473:pathology*; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000502:physiology; D008239:Lysine / Q000031:analogs & derivatives* / Q000502:physiology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000032:analysis / Q000378:metabolism; D015595:Skin Aging / Q000473:pathology*; D013472:Sunlight / Q000009:adverse effects*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: C048496:N(6)-carboxymethyllysine; D004549:Elastin; D009113:Muramidase; D019272:Leukocyte Elastase; D008239:Lysine