Intracellular and extracellular untargeted metabolomics reveal the effect of acute uranium exposure in HK-2 cells

Abstract

Uranium exposure poses a serious threat to the health of occupational populations and the public. Although metabolomics is a promising research approach to study the toxicological mechanisms of uranium exposure, in vitro studies using human cells are scarce. Applying cultured cell metabolomics, we exhaustively analyzed the intracellular and extracellular differential metabolites upon uranium exposure and characterized the possible biological effects of uranium exposure on human kidney cells. Uranium exposure significantly induced disturbance in the amino acid biosynthesis and linoleic acid metabolism of the cells. Cells exposed to uranium produce excessive amounts of arachidonic acid, which has the potential to cause oxidative stress and damage cells. The results provide new evidence for an oxidative stress mechanism of uranium-induced renal cell injury. Cell metabolomics has proven to be a useful diagnostic tool to study the molecular mechanisms of uranium poisoning.

Keywords: Amino acid biosynthesis; Arachidonic acid; Cell metabolomics; Uranium exposure.