Oncotarget

Research Papers:

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

Haidong Yao, Ruifeng Fan, Xia Zhao, Wenchao Zhao, Wei Liu, Jie Yang, Hamid Sattar, Jinxin Zhao, Ziwei Zhang and Shiwen Xu _

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Oncotarget. 2016; 7:57618-57632. https://doi.org/10.18632/oncotarget.11459

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Abstract

Haidong Yao1,*, Ruifeng Fan1,*, Xia Zhao1, Wenchao Zhao1, Wei Liu1,2, Jie Yang1, Hamid Sattar1, Jinxin Zhao1, Ziwei Zhang1 and Shiwen Xu1

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; Ca2+ channels; redox regulation

Received: June 11, 2016 Accepted: August 17, 2016 Published: August 20, 2016

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.


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