Generation of active oxygen species from advanced glycation end-products (AGEs) during ultraviolet light A (UVA) irradiation and a possible mechanism for cell damaging.
Advanced glycation end-products (AGEs) have been reported to be accumulated in dermal skin. However, the role of AGEs in the photoaging of human skin remains unknown, and for this reason, we have examined the interaction between AGEs and ultraviolet A light (UVA) from both the chemical and biological aspects. Previously, we reported that exposing human dermal fibroblasts to UVA in the presence of AGEs that were prepared with bovine serum albumin (BSA) decreased the cell viability due to superoxide anion radical s (.O2(-)) and hydroxyl radicals (.OH) generated by AGEs under UVA irradiation, and active oxygen species are detected with ESR spin-trapping. To identify the active oxygen species in detail and to clarify the cell damaging mechanism, we performed several experiments and the following results were obtained. (1) In ESR spin-trapping, by addition of dimethyl sulfoxide and superoxide dismutase, ESR signals due to .O2(-) -derived DMPO-OOH and .OH-derived DMPO-OH adducts, respectively, were detectable. (2) UVA-irradiated AGEs elevated the lipid peroxide levels in both fibroblasts and liposomes. But the peroxidation in liposomes was inhibited by addition of deferoxamine. (3) Survival of fibroblasts exposed to UVA in the presence of AGEs was elevated by addition of deferoxamine. And finally, (4) survival of fibroblasts was found to be regulated by the level of H2O2. On the basis of these results, we propose a possible mechanism in which AGEs under UVA irradiation generate active oxygen species involving .O2(-), H2O2, and .OH, and the .OH species plays a harmful role in promoting cell damage.
Masaki
H
H
Foundation Research Laboratories, Noevir Co., Ltd., 112-1, Okada-cho, Youkaichi, Shiga 527-8588, Japan.
Okano
Y
Y
Sakurai
H
H
D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000737:chemistry / Q000528:radiation effects; D005609:Free Radicals / Q000737:chemistry; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000032:analysis; D008054:Lipid Peroxides / Q000032:analysis; D008081:Liposomes / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000473:pathology / Q000528:radiation effects*; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D005609:Free Radicals; D017127:Glycation End Products, Advanced; D008054:Lipid Peroxides; D008081:Liposomes; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D003676:Deferoxamine