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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.

SUBMITTER: Labazi M 

PROVIDER: S-EPMC5072523 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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The antioxidant requirement for plasma membrane repair in skeletal muscle.

Labazi Mohamed M   McNeil Anna K AK   Kurtz Timothy T   Lee Taylor C TC   Pegg Ronald B RB   Angeli José Pedro Friedmann JPF   Conrad Marcus M   McNeil Paul L PL  

Free radical biology & medicine 20150403


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 gen  ...[more]

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