Copper impairs hepatic selenoprotein P release

ABSTRACT: Selenoprotein P is a hepatokine which is essential for maintaining systemic selenium homeostasis and is used as serum biomarker for the selenium status in humans. In addition to selenium, also copper homeostasis is mainly regulated by the liver coordinating systemic distribution of copper bound to ceruloplasmin or excreting surplus copper into the bile. Circulating selenium and copper concentrations are most often negatively correlating, e.g. during aging copper levels are increasing while selenium levels are decreasing. Based on these results, we addressed the question of how both trace elements interfere with each other using the liver-derived cell line HepG2. We observed that copper treatment resulted in a substantial increase of intracellular selenium concentrations. In parallel, extracellular SELENOP concentrations were drastically reduced while SELENOP accumulated within the cells. The same observation was made when using primary murine hepatocytes. Indeed, SELENOP was one of the proteins most strongly downregulated by copper in an untargeted secretome approach. Accumulation of hepatic copper is a characteristic of Wilson’s disease. Accordingly, SELENOP levels were decreasing in the serum of LPP rats, a model of Wilson’s disease starting at disease onset. Also, Wilson’s disease patients showed reduced serum SELENOP concentrations when circulating copper concentrations were low. This positive correlation between copper and ceruloplasmin and SELENOP was also observed in a GWAS analysis of EPIC-Potsdam samples identifying SNP rs11708215 as a modulating factor. Our data indicate that under conditions of a suboptimal selenium supply combined with a high copper intake a functional selenium deficit can become even worse because peripheral tissues such as the brain depend on SELENOP for their selenium supply.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Anetta Hartlova  

LAB HEAD: Anetta Härtlova

PROVIDER: PXD036300 | Pride | 2023-07-20

REPOSITORIES: Pride