title: Actinide(IV) Deposits on Bone: Potential Role of the Osteopontin-Thorium Complex.
abstract: In case of a nuclear event, contamination (broad or limited) of the population or of specific workers might occur. In such a senario, the fate of actinide contaminants may be of first concern, in particular with regard to human target organs like the skeleton. To improve our understanding of the toxicological processes that might take place, a mechanistic approach is necessary. For instance, ∼50% of Pu(IV) is known from biokinetic data to accumulate in bone, but the underlining mechanisms are almost unknown. In this context, and to obtain a better description of the toxicological mechanisms associated with actinides(IV), we have undertaken the investigation, on a molecular scale, of the interaction of thorium(IV) with osteopontin (OPN) a hyperphosphorylated protein involved in bone turnover. Thorium is taken here as a simple model for actinide(IV) chemistry. In addition, we have selected a phosphorylated hexapeptide (His-pSer-Asp-Glu-pSer-Asp-Glu-Val) that is representative of the peptidic sequence involved in the bone interaction. For both the protein and the biomimetic peptide, we have determined the local environment of Th(IV) within the bioactinidic complex, combining isothermal titration calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, theoretical calculations with density functional theory, and extended X-ray absorption fine structure spectroscopy at the Th LIII edge. The results demonstrate a predominance of interaction of metal with the phosphate groups and confirmed the previous physiological studies that have highlighted a high affinity of Th(IV) for the bone matrix. Data are further compared with those of the uranyl case, representing the actinyl(V) and actinyl(VI) species. Last, our approach shows the importance of developing simplified systems [Th(IV)-peptide] that can serve as models for more biologically relevant systems.
authors.affiliation: Institut de Chimie de Nice, UMR7272, Université Nice Sophia Antipolis , 28 Avenue Valrose, 06108 Nice, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Creff
authors.affiliation: Institut de Physique Nucléaire d'Orsay, UMR8608, Université Paris XI Orsay , 15 Rue Georges Clemenceau, 91405 Orsay, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Safi
authors.affiliation: Institut de Physique Nucléaire d'Orsay, UMR8608, Université Paris XI Orsay , 15 Rue Georges Clemenceau, 91405 Orsay, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Roques
authors.affiliation: Institut de Chimie de Nice, UMR7272, Université Nice Sophia Antipolis , 28 Avenue Valrose, 06108 Nice, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Michel
authors.affiliation: Institut de Physique Nucléaire d'Orsay, UMR8608, Université Paris XI Orsay , 15 Rue Georges Clemenceau, 91405 Orsay, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Jeanson
authors.affiliation: Synchrotron SOLEIL, L'Orme des Merisiers , BP 48, St Aubin, 91192 Gif sur Yvette, France.
authors.forename: Pier-Lorenzo
authors.initials: PL
authors.lastname: Solari
authors.affiliation: CEA Marcoule, DSV, IBEB, LEPC , 30207 Bagnols sur Cèze, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Basset
authors.affiliation: Institut de Physique Nucléaire d'Orsay, UMR8608, Université Paris XI Orsay , 15 Rue Georges Clemenceau, 91405 Orsay, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Simoni
authors.affiliation: CEA Marcoule, DSV, IBEB, LEPC , 30207 Bagnols sur Cèze, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Vidaud
authors.affiliation: Institut de Chimie de Nice, UMR7272, Université Nice Sophia Antipolis , 28 Avenue Valrose, 06108 Nice, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Den Auwer
mesh_terms: D008671:Actinoid Series Elements / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D006801:Humans; D009842:Oligopeptides / Q000502:physiology; D053495:Osteopontin / Q000737:chemistry / Q000502:physiology*; D017550:Spectroscopy, Fourier Transform Infrared; D013910:Thorium / Q000737:chemistry*
chemical_list: D008671:Actinoid Series Elements; D009842:Oligopeptides; D053495:Osteopontin; D013910:Thorium