International Journal of Molecular Sciences, Vol.14, No.3, 4385-4399, 2013
Different Forms of Selenoprotein M Differentially Affect A beta Aggregation and ROS Generation
Selenoprotein M (SelM), one of the executants of selenium in vivo, is highly expressed in human brain and most probably involved in antioxidation, neuroprotection, and intracellular calcium regulation, which are the key factors for preventing the onset and progression of Alzheimer's disease (AD). In this paper, human SelM was successfully overexpressed in human embryonic kidney cells HEK293T. Sodium selenite (Na2SeO3 0.5 mu mol/L) increased the expression of full-length SelM and inhibited the expression of truncated SelM. The full-length SelM exhibited higher antioxidant activity than its selenocysteine-to-cysteine mutation form SelM', whereas the truncated SelM had an adverse effect that increased the oxidative stress level of cells. When beta-amyloid (A beta(42), an AD relevant peptide) was cotransfected with the empty expression vector, SelM, or SelM' under the induction of 0.5 mu mol/L Na2SeO3, the intracellular A beta(42) aggregation rates were detected to be 57.9% +/- 5.5%, or 22.3% +/- 2.6%, or 26.3% +/- 2.1%, respectively, showing the inhibitory effects on A beta aggregation by the full-length SelM and SelM'. Meanwhile, the intumescentia of mitochondria caused by A beta(42) transfection was significantly mitigated by the cotransfection of SelM or SelM' with A beta(42) under the induction of 0.5 mu mol/L Na2SeO3. On the contrary, cotransfection of SelM and A beta(42) without the induction of Na2SeO3 increased A beta(42) aggregation rate to 65.1% +/- 3.2%, and it could not inhibit the A beta-induced intumescent mitochondria. In conclusion, full-length SelM and SelM. might prevent A beta aggregation by resisting oxidative stress generated during the formation of A beta oligomers in cells.