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dc.contributor.authorYu, Tianzheng
dc.contributor.authorDohl, Jacob
dc.contributor.authorWang, Li
dc.contributor.authorChen, Yifan
dc.contributor.authorGasier, Heath G
dc.contributor.authorDeuster, Patricia A
dc.date.accessioned2020-09-15T18:27:22Z
dc.date.available2020-09-15T18:27:22Z
dc.date.issued2020-09-01
dc.identifier.urihttp://hdl.handle.net/10713/13707
dc.description.abstractBACKGROUND: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the mitochondrial electron transport chain are the primary sources of reactive oxygen species (ROS). Previous studies have shown that severe heat exposure damages mitochondria and causes excessive mitochondrial ROS production that contributes to the pathogenesis of heat-related illnesses. OBJECTIVES: We tested whether the antioxidant curcumin could protect against heat-induced mitochondrial dysfunction and skeletal muscle injury, and characterized the possible mechanism. METHODS: Mouse C2C12 myoblasts and rat flexor digitorum brevis (FDB) myofibers were treated with 5 μM curcumin; adult male C57BL/6J mice received daily curcumin (15, 50, or 100 mg/kg body weight) by gavage for 10 consecutive days. We compared ROS levels and mitochondrial morphology and function between treatment and nontreatment groups under unheated or heat conditions, and investigated the upstream mechanism and the downstream effect of curcumin-regulated ROS production. RESULTS: In C2C12 myoblasts, curcumin prevented heat-induced mitochondrial fragmentation, ROS overproduction, and apoptosis (all P < 0.05). Curcumin treatment for 2 and 4 h at 37°C induced increases in ROS levels by 42% and 59% (dihydroethidium-derived fluorescence), accompanied by increases in NADPH oxidase protein expression by 24% and 32%, respectively (all P < 0.01). In curcumin-treated cells, chemical inhibition and genetic knockdown of NADPH oxidase restored ROS to levels similar to those of controls, indicating NADPH oxidase mediates curcumin-stimulated ROS production. Moreover, curcumin induced ROS-dependent shifting of the mitochondrial fission-fusion balance toward fusion, and increases in mitochondrial mass by 143% and membrane potential by 30% (both P < 0.01). In rat FDB myofibers and mouse gastrocnemius muscles, curcumin preserved mitochondrial morphology and function during heat stress, and prevented heat-induced mitochondrial ROS overproduction and tissue injury (all P < 0.05). CONCLUSIONS: Curcumin regulates ROS hormesis favoring mitochondrial fusion/elongation, biogenesis, and improved function in rodent skeletal muscle. Curcumin may be an effective therapeutic target for heat-related illness and other mitochondrial diseases.en_US
dc.description.urihttps://doi.org/10.1093/jn/nxaa201en_US
dc.language.isoenen_US
dc.publisherAmerican Society for Nutritional Sciencesen_US
dc.relation.ispartofJournal of Nutritionen_US
dc.rightsPublished by Oxford University Press on behalf of the American Society for Nutrition 2020.en_US
dc.subjectNOXen_US
dc.subjectantioxidanten_US
dc.subjectapoptosisen_US
dc.subjectcurcuminen_US
dc.subjectheat stressen_US
dc.subjectmitochondrial fissionen_US
dc.subjectmitochondrial fusionen_US
dc.subjectmyoblasten_US
dc.subjectmyofiberen_US
dc.titleCurcumin Ameliorates Heat-Induced Injury through NADPH Oxidase-Dependent Redox Signaling and Mitochondrial Preservation in C2C12 Myoblasts and Mouse Skeletal Muscleen_US
dc.typeArticleen_US
dc.identifier.doi10.1093/jn/nxaa201
dc.identifier.pmid32692359
dc.source.volume150
dc.source.issue9
dc.source.beginpage2257
dc.source.endpage2267
dc.source.countryUnited States


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