Peroxiredoxin-2 Upregulated by NF-κB Attenuates Oxidative Stress During the Differentiation of Muscle-Derived C2C12 Cells

Aim: Many studies have reported that the generation of reactive oxygen species (ROS) increases during the differentiation of muscle-derived C2C12 cells. Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against oxidative stress. However, the role of Prx-2 in muscle differentiation has not been investigated. Results: In this study, we demonstrated that Prx-2 expression increases during muscle differentiation and regeneration in response to exogenous H(2)O(2). This increase occurs only in myoblast cell lines because no increase in Prx-2 expression was observed in the NIH3T3, MEF, Chang, or HEK293 cell lines. The antioxidants, N-acetyl L-cysteine (NAC) and 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron), both suppressed myogenesis and Prx-2 expression. Moreover, Prx-2 was upregulated at the transcriptional level by NF-kappa B during the differentiation of muscle-derived C2C12 cells. We also found that inhibition of phosphatidylinositol 3-kinase (PI3K) blocks NF-kappa B activation and suppresses Prx-2 expression. Interestingly, Prx-2 knockdown increased the expression levels of other antioxidant enzymes, including all of the other Prx family member, thioredoxin-1 (Trx-1) and catalase, but also enhanced the accumulation of endogenous ROS during muscle differentiation. Innovation: In this study, we demonstrated for the first time that Prx-2 is unregulated during the muscle differentiation and regeneration. Conclusion: Prx-2 is upregulated via the PI3K/NF-kappa B pathway and attenuates oxidative stress during muscle differentiation and regeneration. Antioxid. Redox Signal. 16, 245-261.