Selenoprotein synthesis is not induced by hepatotoxic drugs

Background and AimsMany of the proteins that contain the amino acid selenocysteine are required for optimal defense against cellular stress. As such, one might expect selenoprotein synthesis to persist or be induced upon cellular insult. Because selenocysteine is incorporated by a complex post-transcriptional mechanism, monitoring the transcription of selenoprotein genes is not adequate to understand the regulation of selenoprotein synthesis. We aimed to determine whether selenoprotein synthesis is regulated by the induction of hepatotoxic stress. MethodsWe used hepatotropic clinically relevant drugs to evaluate the regulation of selenoprotein synthesis in human hepatocarcinoma cells. ResultsWe found that two drugs, benzbromarone and sorafenib, caused significant inhibition of selenoprotein synthesis. However, the loss of selenoprotein expression was not specific as total protein synthesis was similarly down-regulated only by benzbromarone and sorafenib. ConclusionsThese results allow us to conclude that these hepatotoxins do not induce or preserve selenoprotein synthesis as a protective mechanism. HighlightsO_LIThe treatment of liver cells with hepatotoxic and hepatotropic compounds does not result in increased synthesis of selenoproteins. C_LIO_LICompounds that induced the canonical oxidative stress response that features NRF2 activation eliminated selenoprotein synthesis. C_LIO_LIThe downregulation of selenoproteins was accompanied by general inhibition of protein synthesis. C_LI