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-κB during the differentiation 
of muscle-derived C2C12 cells. We also found that inhibition of 
phosphatidylinositol 3-kinase (PI3K) blocks NF-κB 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-κB pathway and attenuates 
oxidative stress during muscle differentiation and regeneration.