Selective up-regulation of human selenoproteins in response to oxidative stress.
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.
From the Centre de Génétique Moléculaire, CNRS, UPR3404, 91198 Gif-sur-Yvette, France.
Zahia
Z
Touat-Hamici
From the Centre de Génétique Moléculaire, CNRS, UPR3404, 91198 Gif-sur-Yvette, France.
Yona
Y
Legrain
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.
Anne-Laure
AL
Bulteau
From the Centre de Génétique Moléculaire, CNRS, UPR3404, 91198 Gif-sur-Yvette, France, the Laboratoire de Chimie Analytique Bio-Inorganique et Environnement, CNRS/UPPA, UMR5254, 64000 Pau, France laurent.chavatte@univ-pau.fr.
Laurent
L
Chavatte
D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology; D017279:Selenocysteine / Q000235:genetics / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000094765:Glutathione Peroxidase GPX1
D008565:Membrane Proteins; D016877:Oxidants; D017382:Reactive Oxygen Species; C487710:SELENOS protein, human; D051140:Selenoproteins; D017279:Selenocysteine; D006861:Hydrogen Peroxide; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
Glutathione Peroxidase; Oxidative Stress; SECIS; Selenium; Selenoproteome; Thioredoxin Reductase; Translation Regulation; UGA Recoding