Effect of natural uranium on the UMR-106 osteoblastic cell line: impairment of the autophagic process as an underlying mechanism of uranium toxicity

Natural uranium (U), which is present in our environment, exerts a chemical toxicity, particularly in bone where it accumulates. Generally, U is found at oxidation state +VI in its oxocationic form { U ( VI ) O 2 2 + } in aqueous media. Although U(VI) has been reported to induce cell death in osteob...

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Bibliographic Details
Published in:Archives of toxicology 2017-04, Vol.91 (4), p.1903-1914
Main Authors: Pierrefite-Carle, Valérie, Santucci-Darmanin, Sabine, Breuil, Véronique, Gritsaenko, Tatiana, Vidaud, Claude, Creff, Gaelle, Solari, Pier Lorenzo, Pagnotta, Sophie, Al-Sahlanee, Rasha, Auwer, Christophe Den, Carle, Georges F.
Format: Article
Language:English
Subjects:
Animals
Autophagy - drug effects
Biomedical and Life Sciences
Biomedicine
Calcification, Physiologic - drug effects
Cell Line
Cell Line, Tumor
Dose-Response Relationship, Drug
Environmental Health
Life Sciences
Mineralization
Occupational Medicine/Industrial Medicine
Organ Toxicity and Mechanisms
Osteoblasts - drug effects
Osteoblasts - metabolism
Osteoblasts - pathology
Osteosarcoma - metabolism
Pharmacology/Toxicology
Rats
Thermodynamics
Toxicity
Uranium
Uranium - administration & dosage
Uranium - toxicity
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Summary:Natural uranium (U), which is present in our environment, exerts a chemical toxicity, particularly in bone where it accumulates. Generally, U is found at oxidation state +VI in its oxocationic form { U ( VI ) O 2 2 + } in aqueous media. Although U(VI) has been reported to induce cell death in osteoblasts, the cells in charge of bone formation, the molecular mechanism for U(VI) effects in these cells remains poorly understood. The objective of our study was to explore U(VI) effect at doses ranging from 5 to 600 µM, on mineralization and autophagy induction in the UMR-106 model osteoblastic cell line and to determine U(VI) speciation after cellular uptake. Our results indicate that U(VI) affects mineralization function, even at subtoxic concentrations (
ISSN:0340-5761
1432-0738
DOI:10.1007/s00204-016-1833-5