title: The antioxidant requirement for plasma membrane repair in skeletal muscle.
abstract: 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.
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Labazi
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Anna K
authors.initials: AK
authors.lastname: McNeil
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kurtz
authors.affiliation: Department of Food Science & Technology, The University of Georgia, Athens, GA 30602, USA.
authors.forename: Taylor C
authors.initials: TC
authors.lastname: Lee
authors.affiliation: Department of Food Science & Technology, The University of Georgia, Athens, GA 30602, USA.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Pegg
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
authors.forename: José Pedro Friedmann
authors.initials: JPF
authors.lastname: Angeli
authors.affiliation: Helmholtz Zentrum München, Institute of Developmental Genetics, 85764 Neuherberg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Conrad
authors.affiliation: Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: pmcneil@gru.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: McNeil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D014810:Vitamin E; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase
keywords: Antioxidants; Free radicals; Membrane repair; Skeletal muscle; Vitamin E
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