Electrical Pulse Stimulation Protects C2C12 Myotubes against Hydrogen Peroxide-Induced Cytotoxicity via Nrf2/Antioxidant Pathway

Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a bro...

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Published in:Antioxidants 2024-06, Vol.13 (6), p.716
Main Authors: Pribil Pardun, Sarah, Bhat, Anjali, Anderson, Cody P, Allen, Michael F, Bruening, Will, Jacob, Joel, Pendyala, Ved Vasishtha, Yu, Li, Bruett, Taylor, Zimmerman, Matthew C, Park, Song-Young, Zucker, Irving H, Gao, Lie
Format: Article
Language:English
Subjects:
Acetylcysteine
Adaptation
antioxidant preconditioning
Antioxidants
Cell viability
cellular protection
Cytosol
Cytotoxicity
electrical pulse stimulation
Electrodes
Hydrogen peroxide
Membranes
Mitochondria
Muscle contraction
Musculoskeletal system
Myotubes
Nrf2
Oxidative stress
Oxygen consumption
Physiology
Proteins
Reactive oxygen species
ROS
Skeletal muscle
Spectroscopy
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Summary:Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H O treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox13060716