Selenomethionine Attenuates Hydrogen Peroxide-Induced Oxidative Injury and Modulates Unfolded Protein Response-Related Markers in Murine C2C12 Myoblasts

Abstract

Oxidative stress disrupts skeletal muscle cell survival and proteostasis, thereby compromising animal skeletal muscle health. As an organic selenium source, selenomethionine (SeMet) participates in antioxidant defense and selenoprotein regulation. However, its protective role in hydrogen peroxide (H2O2)-induced injury in C2C12 myoblasts and its association with unfolded protein response (UPR)-related molecular changes remain incompletely understood. This study investigated whether SeMet alleviates H2O2-induced injury in C2C12 myoblasts and whether this effect is associated with UPR-related marker changes. C2C12 myoblasts were treated with H2O2 and SeMet, and cell survival was evaluated using cell viability assays and calcein acetoxymethyl ester/propidium iodide co-staining. The expression of selenoprotein-, UPR-, and apoptosis-related genes was examined by quantitative real-time PCR, and corresponding protein levels were assessed by Western blotting. SeMet improved cell survival under oxidative stress and increased Selenof mRNA and SELENOF protein expression. It also attenuated aberrant changes in endoplasmic reticulum and mitochondrial UPR-related markers and reduced apoptosis-associated molecular responses. These findings indicate that SeMet protects C2C12 myoblasts against H2O2-induced oxidative injury. This protective effect may be associated with changes in SELENOF expression, UPR-related markers, and apoptosis-associated molecular responses, providing molecular evidence for its potential role in maintaining skeletal muscle cell homeostasis.