Selenoprotein synthesis is not induced by hepatotoxic drugs

Abstract

AbstractMany of the proteins that contain the amino acid selenocysteine (Sec) are required for optimal defense against cellular stress. As such, one might expect selenoprotein synthesis to persist or be induced upon cellular insult. Because Sec is incorporated by a complex post-transcriptional mechanism, monitoring the transcription of selenoprotein genes is not adequate to understand the regulation of selenoprotein synthesis. Here we used clinically relevant drugs to evaluate the regulation of selenoprotein synthesis in human hepatocarcinoma (HepG2) cells. We found that two drugs, benzbromarone and sorafenib, caused significant inhibition of selenoprotein synthesis. The loss of selenoprotein expression was not specific as total protein synthesis was similarly down-regulated only by benzbromarone and sorafenib. These results allow us to conclude that these hepatotoxins do not induce or preserve selenoprotein synthesis as a protective mechanism.