title: Protective effect of indole-3-pyruvate against ultraviolet b-induced damage to cultured HaCaT keratinocytes and the skin of hairless mice.
abstract: Previous investigations demonstrated that pyruvate protects human keratinocytes against cell damage stemming from exposure to ultraviolet B (UVB) radiation. This study endeavoured to elucidate the protective capacity of aromatic pyruvates (e.g., phenylpyruvate (PPyr), 4-hydroxyphenylpyruvate (HPPyr), and indole-3-pyruvate (IPyr)) against UVB-induced injury to skin cells, both in vitro and in vivo. Cultured human HaCaT keratinocytes were irradiated with UVB light (60 mJ/cm2) and maintained with or without test compounds (1-25 mM).In addition, the dorsal skin of hairless mice (HR-1) was treated with test compounds (10 μmol) and exposed to UVB light (1 J/cm2) twice [corrected]. The ability of the test compounds to ameliorate UVB-induced cytotoxicity and inflammation was then assessed. Aromatic pyruvates reduced cytotoxicity in UVB-irradiated HaCaT keratinocytes, and also diminished the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6). IPyr was more efficacious than either PPyr or HPPyr. Furthermore, only IPyr inhibited cyclooxygenase-2 (Cox-2) expression at both the mRNA and the protein level in UVB-treated keratinocytes. Topical application of IPyr to the dorsal skin of hairless mice reduced the severity of UVB-induced skin lesions, the augmentation of dermal thickness, and transepithelial water loss. Overproduction of IL-1β and IL-6 in response to UVB radiation was also suppressed in vivo by the topical administration of IPyr. These data strongly suggest that IPyr might find utility as a UVB-blocking reagent in therapeutic strategies to lessen UVB-induced inflammatory skin damage.
authors.affiliation: Functional Biomolecules Research Group, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Reiji
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Functional Biomolecules Research Group, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan; Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Aoki-Yoshida
authors.affiliation: Functional Biomolecules Research Group, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Chise
authors.initials: C
authors.lastname: Suzuki
authors.affiliation: Functional Biomolecules Research Group, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Takayama
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D019610:Cytoprotection / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D007211:Indoles; D017382:Reactive Oxygen Species; C008122:indol-3-yl pyruvic acid; D051546:Cyclooxygenase 2