Authors
Sarah Pribil Pardun, Li Yu, Saadyeh Rashidi, Chittibabu Guda, Lie Gao
Published in
Research square. Oct 08, 2026. Epub Oct 08, 2026.
Abstract
While the benefits of exercise are well-documented, the underlying molecular mechanisms remain to be fully elucidated. Previous research in our lab demonstrated that electrical pulse stimulation (EPS) of cultured C2C12 myotubes activates the Nrf2/antioxidant pathway. In the study presented in this manuscript, we hypothesized that these upregulated antioxidant enzymes are secreted into the conditioned medium (CdM) via extracellular vesicles (EVs) and non-vesicular extracellular nanoparticles (nvEPs). We also hypothesized that these antioxidant-enriched particles protect H9c2 cardiomyocytes from H 2 O 2 -induced damage. EVs/nvEPs were isolated from the CdM of EPS-treated C2C12 cells and compared to those from non-stimulated (NS) cells using differential ultracentrifugation. Transmission electron microscopy (TEM) revealed that the isolated particles displayed a typical morphology, with EVs showing a cup-shaped structure and lipid bilayer membrane, and nvEPs exhibiting a pill-like and amembranous structure with high electron density. Western blot analysis demonstrated that EVs/nvEPs from EPS-C2C12 myotubes contained higher levels of antioxidant proteins (NQO1 and GSTA2) than those isolated from non-stimulated myotubes. Using a CCK-8 viability assay, we found that H9c2 cells pretreated with C2C12-derived nvEPs showed varying degrees of survival following H 2 O 2 challenge. Our findings demonstrate that the EVs/nvEPs released from EPS-C2C12 myotubes contain enriched antioxidant enzymes, which protect cardiomyocytes from oxidative stress.
PMID:
42926683
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.
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