title: Time-course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation.
abstract: Radiation-induced lesion outcomes of normal tissues are difficult to predict. In particular, radiotherapy or local exposure to a radioactive source by accident can trigger strong injury to the skin. The finding of biomarkers is of fundamental relevance for the prediction of lesion apparition and its evolution, and for the settlement of therapeutic strategies. In order to study radiation-induced cutaneous lesions, we developed a mouse model in which the dorsal skin was selectively exposed to ionizing radiation (IR). 2-D difference gel electrophoresis (2-D DIGE) coupled with MS was used to investigate proteins altered in expression and/or PTM in serum. Proteome changes were monitored from 1 day to 1 month postirradiation, at a dose of 40 Gy, in this specific model developing reproducible clinical symptoms ranging from erythema to skin ulceration with wound healing. About 60 proteins (including some isoforms and likely post-translational variants), representing 20 different proteins, that exhibited significant and reproducible kinetic expression changes, were identified using MS and database searches. Several proteins, down- or up-regulated from day one, could prove to be good candidates to prognosticate the evolution of a skin lesion such as necrosis. In addition, we observed shifts in pI of several spot trains, revealing potential PTM changes, which could also serve as indicators of irradiation or as predictors of lesion severity.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Fontenay aux Roses, France. olivier.guipaud@irsn.fr
authors.forename: Olivier
authors.initials: O
authors.lastname: Guipaud
authors.forename: Valérie
authors.initials: V
authors.lastname: Holler
authors.forename: Valérie
authors.initials: V
authors.lastname: Buard
authors.forename: Georges
authors.initials: G
authors.lastname: Tarlet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Royer
authors.forename: Joëlle
authors.initials: J
authors.lastname: Vinh
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000528:radiation effects*; D015180:Electrophoresis, Gel, Two-Dimensional; D005720:Gamma Rays / Q000009:adverse effects; D007526:Isoelectric Point; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism* / Q000528:radiation effects*; D040901:Proteomics; D011853:Radiobiology; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*
chemical_list: D001798:Blood Proteins; D020543:Proteome