title: Protective effect of geranylgeranylacetone against radiation-induced delayed effects on human keratinocytes.
abstract: Skin exposure to ionizing radiation affects the normal wound healing process. We investigated the beneficial effects of a pharmacological treatment with geranylgeranylacetone (GGA) on keratinocytes using in vitro scratch wound injury assay in nonirradiated and irradiated conditions. Irradiation affected the wound closure of keratinocytes 24 h after scratch injury, whereas re-epithelialization was markedly accelerated after GGA treatment when compared to nontreated keratinocytes. We demonstrated that GGA treatment increased migration of human epidermal keratinocytes and this migratory property was not related to RhoA signaling. Interestingly, Western blot analysis revealed that GGA treatment down-regulated caspase 3 active form expression and up-regulated the activated phenotype by inducing both keratin 6 (K6) expression and interleukin-1β (IL-1β) release without modification of the differentiate phenotype. Finally, the proteomic profiling was performed on keratinocytes, showing that global protein changes occurred after irradiation of keratinocytes treated or untreated with GGA.
authors.affiliation: IRSN, Institut de Radioprotection et de Sureté Nucléaire, Laboratoire de Radio Pathologie et de Thérapie Expérimentale, BP 17, 92262 Fontenay-aux-Roses Cedex, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Isoir
authors.forename: Telma
authors.initials: T
authors.lastname: Roque
authors.forename: Claire
authors.initials: C
authors.lastname: Squiban
authors.forename: Fabien
authors.initials: F
authors.lastname: Milliat
authors.forename: Philippe
authors.initials: P
authors.lastname: Mondon
authors.forename: Claire
authors.initials: C
authors.lastname: Mas-Chamberlin
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Olivier
authors.initials: O
authors.lastname: Guipaud
authors.forename: Radia
authors.initials: R
authors.lastname: Tamarat
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004224:Diterpenes / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D040901:Proteomics; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013997:Time Factors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D004224:Diterpenes; D011837:Radiation-Protective Agents; D020742:rhoA GTP-Binding Protein; C031049:geranylgeranylacetone