Abstract: 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 μmol/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 β-amyloid (Aβ42, an AD relevant peptide) was cotransfected with the empty expression vector, SelM, or SelM' under the induction of 0.5 μmol/L Na2SeO3, the intracellular Aβ42 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 Aβ aggregation by the full-length SelM and SelM'. Meanwhile, the intumescentia of mitochondria caused by Aβ42 transfection was significantly mitigated by the cotransfection of SelM or SelM′ with Aβ42 under the induction of 0.5 μmol/L Na2SeO3. On the contrary, cotransfection of SelM and Aβ42 without the induction of Na2SeO3 increased Aβ42 aggregation rate to 65.1% ± 3.2%, and it could not inhibit the Aβ-induced intumescent mitochondria. In conclusion, full-length SelM and SelM¢ might prevent Aβ aggregation by resisting oxidative stress generated during the formation of Aβ oligomers in cells.
Keywords: selenoprotein M (SelM); antioxidant; neuroprotection; reactive oxygen species (ROS)
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Chen, P.; Wang, R.-R.; Ma, X.-J.; Liu, Q.; Ni, J.-Z. Different Forms of Selenoprotein M Differentially Affect Aβ Aggregation and ROS Generation. Int. J. Mol. Sci. 2013, 14, 4385-4399.
Chen P, Wang R-R, Ma X-J, Liu Q, Ni J-Z. Different Forms of Selenoprotein M Differentially Affect Aβ Aggregation and ROS Generation. International Journal of Molecular Sciences. 2013; 14(3):4385-4399.
Chen, Ping; Wang, Ruo-Ran; Ma, Xiao-Jie; Liu, Qiong; Ni, Jia-Zuan. 2013. "Different Forms of Selenoprotein M Differentially Affect Aβ Aggregation and ROS Generation." Int. J. Mol. Sci. 14, no. 3: 4385-4399.