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Cytoprotective Role of Nrf2 in Electrical Pulse Stimulated C2C12 Myotube
- Source :
- PLoS ONE, Vol 10, Iss 12, p e0144835 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS) production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2) transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS) of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms) stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC) significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.
- Subjects :
- medicine.medical_specialty
Cell Survival
NF-E2-Related Factor 2
Muscle Fibers, Skeletal
lcsh:Medicine
Apoptosis
Biology
medicine.disease_cause
digestive system
environment and public health
Antioxidants
Cell Line
Mice
chemistry.chemical_compound
Internal medicine
medicine
Animals
Viability assay
Muscle, Skeletal
lcsh:Science
Reactive nitrogen species
chemistry.chemical_classification
Reactive oxygen species
Multidisciplinary
GCLM
Myogenesis
lcsh:R
Skeletal muscle
respiratory system
Reactive Nitrogen Species
Electric Stimulation
Oxidative Stress
medicine.anatomical_structure
Endocrinology
chemistry
Cytoprotection
lcsh:Q
medicine.symptom
Reactive Oxygen Species
Oxidative stress
Research Article
Signal Transduction
Muscle contraction
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....0cab4fd07ba9b5b31ed2faa8f6ff8305