ECE2008 Poster Presentations Diabetes and cardiovascular diseases (90 abstracts)
Background: Selenoproteins contain the 21st proteinogenic amino acid selenocysteine (Sec) and exert important biological functions. Selenoprotein S (SelS) has only recently been identified and appears to be implicated in type 2 diabetes and inflammation. In vitro studies have shown that SelS expression is controlled by circulating cytokine and glucose levels. Mechanistically, SelS participates in the retro-translocation during quality control in the ER and the ER-associated degradation pathway.
Hypothesis: SelS is a selenoprotein and as such its translation depends on the selenium (Se) supply. mRNA levels may fail to reliably reflect SelS protein levels, especially if the organism is stressed by an acute phase response (APR). Therefore, Se-deficiency and/or APR may impair the regular SelS expression.
Material and methods: We have injected male and female mice on different Se status with lipopolysaccharide (LPS) to induce an APR. SelS levels were determined by qPCR and Western blot analysis in liver, fat and muscle.
Results: SelS biosynthesis turned out to be intensively regulated on the posttranscriptional level by both the APR and the Se status of the organism. In liver, fat and muscle tissue, we observed a tissue-specific increase of SelS protein concentrations in well-supplied animals (up to 20-fold induction of SelS protein) but only marginal effects on SelS mRNA. This Se-dependent expression was characteristically altered during the APR.
Conclusion: Since SelS is involved in glucose metabolism, diabetes and oxidative stress defence, sufficient dietary Se is needed for the regular biosynthesis of SelS, and thereby may impact onto the individual insulin sensitivity and APR.
Supported by Deutsche Krebshilfe (10-1792 SchoII) and DFG (SCHO 849/2-1).