Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts

Satoshi Haramizu, Shinichi Asano, David C. Butler, David A. Stanton, Ameena Hajira, Junaith Mohamed, Stephen Alway

Research output: Contribution to journalArticle

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Abstract

High levels of reactive oxygen species (ROS) contribute to muscle cell death in aging and disuse. We have previously found that resveratrol can reduce oxidative stress in response to aging and hindlimb unloading in rodents in vivo, but it was not known if resveratrol would protect muscle stem cells during repair or regeneration when oxidative stress is high. To test the protective role of resveratrol on muscle stem cells directly, we treated the C2C12 mouse myoblast cell line with moderate (100 μM) or very high (1 mM) levels of H2O2 in the presence or absence of resveratrol. The p21 promoter activity declined in myoblasts in response to high ROS, and this was accompanied a greater nuclear to cytoplasmic translocation of p21 in a dose-dependent matter in myoblasts as compared to myotubes. Apoptosis, as indicated by TdT-mediated dUTP nick-end labeling, was greater in C2C12 myoblasts as compared to myotubes (P<.05) after treatment with H2O2. Caspase-9, -8 and -3 activities were elevated significantly (P<.05) in myoblasts treated with H2O2. Myoblasts were more susceptible to ROS-induced oxidative stress than myotubes. We treated C2C12 myoblasts with 50 μM of resveratrol for periods up to 48 h to determine if myoblasts could be rescued from high-ROS-induced apoptosis by resveratrol. Resveratrol reduced the apoptotic index and significantly reduced the ROS-induced caspase-9, -8 and -3 activity in myoblasts. Furthermore, Bcl-2 and the Bax/Bcl-2 ratio were partially rescued in myoblasts by resveratrol treatment. Similarly, muscle stem cells isolated from mouse skeletal muscles showed reduced Sirt1 protein abundance with H2O2 treatment, but this could be reversed by resveratrol. Reduced apoptotic susceptibility in myoblasts as compared to myotubes to ROS is regulated, at least in part, by enhanced p21 promoter activity and nuclear p21 location in myotubes. Resveratrol confers further protection against ROS by improving Sirt1 levels and increasing antioxidant production, which reduces mitochondrial associated apoptotic signaling, and cell death in myoblasts.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalJournal of Nutritional Biochemistry
Volume50
DOIs
StatePublished - Dec 1 2017
Externally publishedYes

Fingerprint

Oxidative stress
Myoblasts
Oxidative Stress
Reactive Oxygen Species
Skeletal Muscle Fibers
Muscle
Muscle Cells
Stem cells
Caspase 9
Cell death
Stem Cells
Caspase 8
Aging of materials
resveratrol
Apoptosis
Cell Death
Hindlimb Suspension
Unloading
Labeling
Repair

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts. / Haramizu, Satoshi; Asano, Shinichi; Butler, David C.; Stanton, David A.; Hajira, Ameena; Mohamed, Junaith; Alway, Stephen.

In: Journal of Nutritional Biochemistry, Vol. 50, 01.12.2017, p. 103-115.

Research output: Contribution to journalArticle

Haramizu, Satoshi ; Asano, Shinichi ; Butler, David C. ; Stanton, David A. ; Hajira, Ameena ; Mohamed, Junaith ; Alway, Stephen. / Dietary resveratrol confers apoptotic resistance to oxidative stress in myoblasts. In: Journal of Nutritional Biochemistry. 2017 ; Vol. 50. pp. 103-115.
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AU - Mohamed, Junaith

AU - Alway, Stephen

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