Selective Up-regulation of Human Selenoproteins in Response to Oxidative Stress |
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Authors: | Zahia Touat-Hamici Yona Legrain Anne-Laure Bulteau Laurent Chavatte |
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Affiliation: | From the ‡Centre de Génétique Moléculaire, CNRS, UPR3404, 91198 Gif-sur-Yvette, France.;the §Centre de Recherche Institut Cochin, INSERM U567, CNRS UMR 8104, 75005 Paris, France, and ;the ¶Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, CNRS/UPPA, UMR5254, 64000 Pau, France |
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Abstract: | Selenocysteine 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 selenocysteine insertion sequence 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 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 up-regulation of selenoproteins, protected HEK293 cells from reactive oxygen species formation. Furthermore, in response to oxidative stress, we identified a selective up-regulation of several selenoproteins involved in antioxidant defense (Gpx1, Gpx4, TR1, SelS, SelK, and Sps2). Interestingly, the response was more efficient when selenium was limiting. Although a modest change in mRNA levels was noted, we identified a novel translational control mechanism stimulated by oxidative stress that is characterized by up-regulation of UGA-selenocysteine recoding efficiency and relocalization of SBP2, selenocysteine-specific elongation factor, and L30 recoding factors from the cytoplasm to the nucleus. |
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Keywords: | Glutathione Peroxidase Oxidative Stress Selenium Thioredoxin Reductase Translation Regulation SECIS UGA Recoding Selenoproteome |
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