title: Selenoprotein W redox-regulated Ca2+ channels correlate with selenium deficiency-induced muscles Ca2+ leak.
abstract: Selenium (Se) deficiency induces Ca2+ 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 Ca2+ leak and oxidative stress (P < 0.05) injured the ultrastructure of the sarcoplasmic reticulum (SR) and mitochondria; decreased the levels of the Ca2+ channels, SERCA, SLC8A, CACNA1S, ORAI1, STIM1, TRPC1, and TRPC3 (P < 0.05); and increased the levels of Ca2+ channel PMCA (P < 0.05). Similarly, SelW knockdown also induced Ca2+ leak from the SR and cytoplasm; increased mitochondrial Ca2+ levels and oxidative stress; injured SR and mitochondrial ultrastructure; decreased levels of SLC8A, CACNA1S, ORA1, TRPC1, and TRPC3; and caused abnormal activities of Ca2+ channels in response to inhibitors in myoblasts and chicken embryos. Thus, both Se deficiency and SelW knockdown induced Ca2+ leak, oxidative stress, and Ca2+ channel reduction. In addition, Ca2+ levels and the expression of the Ca2+ 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 Ca2+ channels, SelW knockdown closely correlated Se deficiency with Ca2+ leak in muscles. The redox regulation role of SelW is crucial in Se deficiency-induced Ca2+ leak in muscles.
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.|The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Hamid
authors.initials: H
authors.lastname: Sattar
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Jinxin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Medicine, Northeast Agricultural University, Harbin, P. R. China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Xu
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D002114:Calcinosis; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D015220:Calcium Channels / Q000737:chemistry*; D002642:Chick Embryo; D002645:Chickens; D003600:Cytosol / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012643:Selenium / Q000172:deficiency*; D051151:Selenoprotein W / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D015220:Calcium Channels; D051151:Selenoprotein W; D012643:Selenium; D002118:Calcium; D000111:Acetylcysteine
keywords: Ca2+ channels; Ca2+ leak; redox regulation; selenium deficiency; selenoprotein W