Deciphering the uranium target proteins in human dopaminergic SH-SY5Y cells.

Deciphering the uranium target proteins in human dopaminergic SH-SY5Y cells. Arch Toxicol. 2019 Jun 20;: Authors: Vidaud C, Robert M, Paredes E, Ortega R, Avazeri E, Jing L, Guigonis JM, Bresson C, Malard V Abstract Uranium (U) is the heaviest naturally occurring element ubiquitously present in the Earth's crust. Human exposure to low levels of U is, therefore, unavoidable. Recently, several studies have clearly pointed out that the brain is a sensitive target for U, but the mechanisms leading to the observed neurological alterations are not fully known. To deepen our knowledge of the biochemical disturbances resulting from U(VI) toxicity in neuronal cells, two complementary strategies were set up to identify the proteins that selectively bind U(VI) in human dopaminergic SH-SY5Y cells. The first strategy relies on the selective capture of proteins capable of binding U(VI), using immobilized metal affinity chromatography, and starting from lysates of cells grown in a U(VI)-free medium. The second strategy is based on the separation of U-enriched protein fractions by size-exclusion chromatography, starting from lysates of U(VI)-exposed cells. High-resolution mass spectrometry helped us to highlight 269 common proteins identified as the urano-proteome. They were further analyzed to characterize their cellular localization and biological functions. Four canonical pathways, related to the protein ubiquitination system, gluconeogenesis, gl...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research