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 radiationinduced 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.

Plasma biomarkers of mouse aging

“…Prx-2 resides in cytoplasm and is not a typical secreted protein, thus it may be derived from ruptured cells. However, it has been detected in mouse serum by 2-DE (Guipaud et al 2007) with a similar Mw and pI as reported here. Interestingly, serum Prx-2 levels have been found to decrease after mice have been exposed to skin irradiation (Guipaud et al 2007).…”

“…However, it has been detected in mouse serum by 2-DE (Guipaud et al 2007) with a similar Mw and pI as reported here. Interestingly, serum Prx-2 levels have been found to decrease after mice have been exposed to skin irradiation (Guipaud et al 2007). In Caenorhabditis elegans, Prx protects against oxidative stress and heat stress, as well as promotes longevity (OlÃhovà et al 2008).…”

Cytokinesis-Block Micronucleus (Cbmn) Assay/CBMN Cytome Assay in Human Lymphocytes After in Vitro Irradiation and Its Use in Biodosimetry

“…Recently, several new biodosimetric methods overcoming some of these limitations have been proposed, including protein marker (e.g. H2AX) or serum protein analyses (1,10,17). Nevertheless, these assays are being developed and have not yet been tested in a real triage situation (1).…”

Pyruvate carboxylase as a sensitive protein biomarker for exogenous steroid chemicals

“…The images were analyzed using Image Master 2D Platinum 7.0 (GE Healthcare) software (Guipaud et al, 2007). Gels from male and female fish (n ¼ 6 gels/group) were analyzed separately (Supporting Information).…”