Selenoprotein W redox-regulated Ca(2+) channels correlate with selenium deficiency-induced muscles Ca(2+) leak

Selenium (Se) deficiency induces Ca(2+) leak and calcification in mammal skeletal muscles; however, the exact mechanism is still unclear. In the present study, both Se-deficient chicken muscle models and selenoprotein W (SelW) gene knockdown myoblast and embryo models were used to study the mechanism. The results showed that Se deficiency-induced typical muscular injuries accompanied with Ca(2+) leak and oxidative stress (P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca(2+) channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P < 0.05); and increased the levels of Ca(2+) channel PMCA (P < 0.05). Similarly, SelW knockdown also induced Ca(2+) leak from the SR and cytoplasm; increased mitochondrial Ca(2+) levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca(2+) channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdown induced Ca(2+) leak, oxidative stress, and Ca(2+) channel reduction. In addition, Ca(2+) levels and the expression of the Ca(2+) channels, RyR1, SERCA, CACNA1S, TRPC1, and TRPC3 were recovered to normal levels by N-acetyl-L-cysteine (NAC) treatment compared with SelW knockdown cells. Thus, with regard to the decreased Ca(2+) channels, SelW knockdown closely correlated Se deficiency with Ca(2+) leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca(2+) leak in muscles.