Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency-induced muscles Ca2+ leak

// Haidong Yao 1,* , Ruifeng Fan 1,* , Xia Zhao 1 , Wenchao Zhao 1 , Wei Liu 1,2 , Jie Yang 1 , Hamid Sattar 1 , Jinxin Zhao 1 , Ziwei Zhang 1 and Shiwen Xu 1 1 Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China 2 The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, P. R. China * These authors have contributed equally to this work Correspondence to: Shiwen Xu, email: // Ziwei Zhang, email: // Keywords : selenium deficiency; Ca2+ leak; selenoprotein W; Ca 2+ channels; redox regulation Received : June 11, 2016 Accepted : August 17, 2016 Published : August 20, 2016 Abstract 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.