Selective up-regulation of human selenoproteins in response to oxidative stress

Abstract

Selenocysteinse is inserted into selenoproteins via the translational recoding of a UGA codon, normally used as a stop signal. This process depends on the nature of the SECIS element located in the 3'UTR of selenoprotein mRNAs, selenium bioavailability, and possibly exogenous stimuli. To further understand the function and regulation of selenoproteins in antioxidant defense and redox homeostasis, we have investigated how oxidative stress influences selenoprotein expression as a function of different selenium concentrations. We found that selenium supplementation of the culture media, which resulted in a hierarchical upregulation of selenoproteins, protected HEK293 cells from ROS formation. Furthermore, in response to oxidative stress, we identified a selective upregulation of several selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK and Sps2). Interestingly, the response was more efficient when selenium was limiting. While a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by upregulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, EFsec and L30 recoding factors from cytoplasm to nucleus.