Tissue-specific regulation of the expression on individual glutathione peroxidases

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The most effective parameter determining the activity of selenoproteins is the availability of selenium. Both, the strict hierarchy by which selenoproteins are supplied with selenium and the sometimes unique tissue specificity, however, point to additional regulatory mechanisms. These may function at translational or trancriptional levels. mRNA stability may be regulated by RNA-binding proteins which by themselves respond to selenium and/or differ in their affinities to other factors (tRNA, GTP) stabilizing the putative mRNA/protein complex.Transcription may be regulated by tissue-specific transcription factors. RNA-binding proteins are to be identified by their interaction with the 3'-untranslated regions, bearing the Secis elements, of two selected glutathione peroxidases, cGPx and GI-GPx. Responsive elements and factors binding to them will be found by using the available PHGPx promoter and the GI-GPx promoter which is to be cloned. Both subsequently shortened promoters will be coupled to reporter genes and their activities studied in cells from different tissue transfected with the resulting constructs. With these approaches an explanation should be found for the different stability of the mRNA for at least two glutathione peroxidases under selenium limiting conditions as well as for their unique tissue distribution.