Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
3449572
Reference Type
Journal Article
Title
Effect of natural uranium on the UMR-106 osteoblastic cell line: Impairment of the autophagic process as an underlying mechanism of uranium toxicity
Author(s)
Pierrefite-Carle, V; Santucci-Darmanin, S; Breuil, V; Gritsaenko, T; Vidaud, C; Creff, G; Solari, PL; Pagnotta, S; Al-Sahlanee, R; Auwer, CD; Carle, GF
Year
2017
Is Peer Reviewed?
Yes
Journal
Archives of Toxicology
ISSN:
0340-5761
EISSN:
1432-0738
Volume
91
Issue
4
Page Numbers
1903-1914
Language
English
PMID
27585666
DOI
10.1007/s00204-016-1833-5
Web of Science Id
WOS:000398819200027
Abstract
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 [Formula: see text] 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 (<100 µM). The combination of thermodynamic modeling of U with EXAFS data in the culture medium and in the cells clearly indicates the biotransformation of U(VI) carbonate species into a meta-autunite phase upon uptake by osteoblasts. We next assessed U(VI) effect at 100 and 300 µM on autophagy, a survival process triggered by various stresses such as metal exposure. We observed that U(VI) was able to rapidly activate autophagy but an inhibition of the autophagic flux was observed after 24 h. Thus, our results indicate that U(VI) perturbs osteoblastic functions by reducing mineralization capacity. Our study identifies for the first time U(VI) in the form of meta-autunite in mammalian cells. In addition, U(VI)-mediated inhibition of the autophagic flux may be one of the underlying mechanisms leading to the decreased mineralization and the toxicity observed in osteoblasts.
Tags
IRIS
•
Uranium
Pubmed
WOS
Additional strategies
Uranium Literature Search Update 3/2017
Toxnet
Uranium Literature Search Update 7/2018
PubMed
WOS
Uranium Literature Search Update 4/2020
PubMed
•
Uranium Toxicological Review
Screening
Supplementary Material
Mechanistic -r MOA
Date limited literature search 2011-2021
WOS
Pubmed
Scopus
New to this search
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity