Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 84, Issue -, Pages 246-253Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.03.016
Keywords
Vitamin E; Antioxidants; Membrane repair; Skeletal muscle; Free radicals
Funding
- NIH [1R21AR060565, 1R21DK090703]
- Deutsche Forschungsgemeinschaft [DFGCO 291/2-3, CO 291/5-1]
- Alexander von Humboldt-Stiftung
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Vitamin E (VE) deficiency results in pronounced muscle weakness and atrophy but the cell biological mechanism of the pathology is unknown. We previously showed that VE supplementation promotes membrane repair in cultured cells and that oxidants potently inhibit repair. Here we provide three independent lines of evidence that VE is required for skeletal muscle myocyte plasma membrane repair in vivo. We also show that when another lipid-directed antioxidant, glutathione peroxidase 4 (Gpx4), is genetically deleted in mouse embryonic fibroblasts, repair fails catastrophically, unless cells are supplemented with VE. We conclude that lipid-directed antioxidant activity provided by VE, and possibly also Gpx4, is an essential component of the membrane repair mechanism in skeletal muscle. This work explains why VE is essential to muscle health and identifies VE as a requisite component of the plasma membrane repair mechanism in vivo. (C) 2015 Elsevier Inc. All rights reserved.
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