Photo-enhanced modification of human skin elastin in actinic elastosis by N(epsilon)-(carboxymethyl)lysine, one of the glycoxidation products of the Maillard reaction.
Long-term incubation of proteins with glucose leads to the formation of advanced glycation end products (AGEs), which are characterized by fluorescence, brown color, and cross-linking. Formation of AGEs in vitro requires oxygen and is dependent on transition metal-catalyzed oxidation of glucose or Amadori products. AGEs are thought to be involved in aging and age-enhanced diseases such as diabetic complications, atherosclerosis, dialysis-related amyloidosis, and Alzheimer's disease. Chronic exposure of the skin to sunlight induces hyperplasia of the elastic tissue in the upper dermis known as actinic elastosis. Herein we used a monoclonal anti-AGE antibody (6D12) whose epitope is N(epsilon)-(carboxymethyl)lysine (CML), one of the glycoxidation products of AGEs, and demonstrated that the lesions of actinic elastosis were modified by CML. Further immunohistochemical and immunoelectron microscopic examination with 6D12 demonstrated CML accumulates predominantly in elastic fibers especially in the amorphous electron-dense materials corresponding to photo-induced degenerated area rather than the electron-lucent region. Immunochemical analyses with enzyme-linked immunosorbent assay (ELISA) of elastase-soluble fractions demonstrated that the CML levels of the sun-exposed area were significantly higher than those of the sun-unexposed area. We conclude that ultraviolet-induced oxidation may accelerate CML formation in actinic elastosis of photoaged skin.
Mizutari
K
K
Department of Dermatology, Kumamoto University School of Medicine, Honjo, Japan.
Ono
T
T
Ikeda
K
K
Kayashima
K
K
Horiuchi
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004549:Elastin / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D010787:Photosensitivity Disorders / Q000378:metabolism; D012867:Skin / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D015595:Skin Aging / Q000528:radiation effects; D014466:Ultraviolet Rays
D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D004549:Elastin; D008239:Lysine