The recently described gastrointestinal
glutathione peroxidase (GI-GPx) is the fourth member of the family of the selenoenzymes
glutathione peroxidases (GPx). In contrast to the more uniform distribution of, for example, the classical
glutathione peroxidase (cGPx), it is expressed exclusively in the gastrointestinal tract and has, therefore, been suggested to function as a primary barrier against alimentary hydroperoxides. In order to get an idea of its relative importance we investigated its position in the hierarchy of
selenoprotein expression. The
selenium-dependent expression of GI-GPx was analyzed in comparison with that of other GPx types at the level of
mRNA and
protein in HepG2 and CaCo-2 cells. Furthermore, the
selenocysteine insertion sequence (SECIS) efficiencies of GI-GPx,
phospholipid hydroperoxide glutathione peroxidase (PHGPx) and cGPx in response to
selenium were determined by a reporter-gene assay in human
hepatoma cells and baby hamster kidney cells. GI-GPx
mRNA levels increased during
selenium deficiency, whereas cGPx
mRNA levels decreased and PHGPx
mRNA levels remained almost unaffected. In cells grown in
selenium-poor media, all GPx-types were low in both activity and immunochemical reactivity. Upon
selenium repletion immunoreactive GI-GPx
protein reached a plateau after 10 h, whereas cGPx started to be expressed at 24 h and did not reach its maximum level before 3 days. SECIS efficiencies decreased in the order PHGPx > cGPx > GI-GPx. The augmentation of SECIS efficiencies by
selenium was highest for cGPx and intermediate for PHGPx, whereas it was marginal for GI-GPx. The high mRNA stability under
selenium restriction, the speed of biosynthesis upon
selenium repletion and the marginal effect of
selenium on the SECIS efficiency indicate that of the GPx isotypes, GI-GPx ranks highest in the hierarchy of
selenoproteins and point to a vital role of GI-GPx in the gastrointestinal tract.