Curcumin Ameliorates Heat-Induced Injury through NADPH Oxidase-Dependent Redox Signaling and Mitochondrial Preservation in C2C12 Myoblasts and Mouse Skeletal Muscle.

dc.contributor.author

Yu, Tianzheng

dc.contributor.author

Dohl, Jacob

dc.contributor.author

Wang, Li

dc.contributor.author

Chen, Yifan

dc.contributor.author

Gasier, Heath G

dc.contributor.author

Deuster, Patricia A

dc.date.accessioned

2021-12-21T20:49:18Z

dc.date.available

2021-12-21T20:49:18Z

dc.date.issued

2020-09

dc.date.updated

2021-12-21T20:49:17Z

dc.description.abstract

Background

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.
dc.identifier

5874421

dc.identifier.issn

0022-3166

dc.identifier.issn

1541-6100

dc.identifier.uri

https://hdl.handle.net/10161/24091

dc.language

eng

dc.publisher

Oxford University Press (OUP)

dc.relation.ispartof

The Journal of nutrition

dc.relation.isversionof

10.1093/jn/nxaa201

dc.subject

Muscle, Skeletal

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Mitochondria

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Myoblasts

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Animals

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Mice, Inbred C57BL

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Mice

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Rats

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Rats, Sprague-Dawley

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Curcumin

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Signal Transduction

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Oxidation-Reduction

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Male

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Hot Temperature

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NADPH Oxidases

dc.title

Curcumin Ameliorates Heat-Induced Injury through NADPH Oxidase-Dependent Redox Signaling and Mitochondrial Preservation in C2C12 Myoblasts and Mouse Skeletal Muscle.

dc.type

Journal article

duke.contributor.orcid

Gasier, Heath G|0000-0001-5895-4542

pubs.begin-page

2257

pubs.end-page

2267

pubs.issue

9

pubs.organisational-group

School of Medicine

pubs.organisational-group

Anesthesiology

pubs.organisational-group

Duke

pubs.organisational-group

Clinical Science Departments

pubs.publication-status

Published

pubs.volume

150

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