Pentosidine in advanced glycation end-products (AGEs) during UVA irradiation generates active oxygen species and impairs human dermal fibroblasts.
Our previous study reported that advanced glycation end-products (AGE)-modified BSA produced active oxygen species, *O2-, H2O2, and *OH under UVA irradiation and enhanced the cytotoxicity of UVA light. We examined whether pentosidine in AGE-modified BSA was involved in one of the mechanisms generating the active oxygen species. In biological investigations, fibroblasts exposed to UVA (20 J/cm2) in the presence of pentosidine-rich compounds (PRCs), which were prepared with L-arginine, L-lysine and glucose, showed a time-dependent leakage of the cytosolic enzyme LDH. In addition, release of LDH was suppressed by addition of DMSO and deferoxamine under UVA irradiation. From these results, it was determined that PRCs exposed to UVA damaged the plasma membrane of human dermal fibroblasts due to the conversion of *OH from H2O2 via a Fenton-like reaction. These features of PRCs exposed to UVA were consistent with those of AGE-modified BSA. In an ESR study, PRCs under UVA irradiation yielded DMPO-OH (DMPO-OH adduct) using DMPO as a spin-trapping reagent. *O2- generation from UVA-irradiated PRCs was also indicated by the combination of NBT reduction and SOD. When PRCs were exposed to UVA light controlled with a long-pass filter, WG-360, it was found that their production of *O2- was prohibited less than 50% in the NBT reduction assay. The *O2- production profile of PRCs depending on the wavelength of UVA light was similar to that of AGE-modified BSA. Furthermore, it was found that the H2O2 level was increased by PRCs exposed to UVA. These results indicated that pentosidine is an important factor of AGE-modified BSA in active oxygen generation under UVA irradiation.
Okano
Y
Y
Kobe Research Laboratories, Noevir Company, Limited, 13-1 Port Island, Naka-machi 6-chome, Chuo-ku, 650-8521, Kobe, Japan.
Masaki
H
H
Sakurai
H
H
D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008239:Lysine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000528:radiation effects; D012867:Skin / Q000166:cytology*; D012879:Skin Physiological Phenomena / Q000187:drug effects / Q000528:radiation effects*; D013481:Superoxides / Q000378:metabolism; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D013481:Superoxides; D012710:Serum Albumin, Bovine; D001120:Arginine; D006861:Hydrogen Peroxide; C062187:pentosidine; D007770:L-Lactate Dehydrogenase; D008239:Lysine