Uranium in its depleted form is widely used both in industry and the military. Although it is low in radioactivity, its chemical toxicity is well documented in studies of reactivity of uranyl ions in a variety of biological models. These show the formation of complexes with important ligands and induction of oxidative stress. Thus, understanding the mechanisms of its metabolism, homeostasis and toxicity on humans and other organisms is of the utmost importance. The aim of the MOTAUR (Molecular targets of uranium in some aquatic organisms) project was to develop a series of novel analytical methods that could identify and quantify the species resulting from the interaction of uranyl ions with the proteome and metabolome. To date, most in vitro studies of uranyl ions have been concerned with isolated proteins. MOTAUR, however, addressed the problem of uranium-protein interactions within a system, including protein-uranyl ion-protein complex interactions. Results showed that uranyl ions act on a serum protein network as a binding ligand rather than choosing single molecular targets. Therefore, the proteomics data was characterised in terms of molecular and biological function of the proteins involved, such as coagulation cascades, mineralisation and metal ions binding. Proteins identified on the basis of their reactivity towards uranyl ions revealed 32 responsible for protein binding and 34 for interactions with the ions. This finding was supported by information in the literature, which indicated that uranyl ions can be bound in both cationic and anionic form. Researchers also identified proteins involved in the homeostasis of other ions, mainly calcium. Some contained gamma-carboxyglutamic acid-rich domains, which showed a strong affinity toward calcium ions and have not previously been considered as targets of uranyl ions in serum. In the uranyl ions-dependent network, eight proteins are known for binding heparin, which, as a sulphate-rich ligand, can easily interact with the uranyl ion. Scientists therefore determined the relationship of other elements present in serum, including calcium, phosphorus and magnesium, with uranium-dependent proteins. The difference in isolated protein pattern in bovine and foetal sera systems showed different molecular mechanisms for binding of uranyl ions, thereby demonstrating the validity of the MOTAUR method in a variety of sera samples.
Molecular targets, uranium, chemical speciation, toxicity, uranyl ions, MOTAUR