title: Peroxiredoxin-2 upregulated by NF-κB attenuates oxidative stress during the differentiation of muscle-derived C2C12 cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  In this study, we demonstrated for the first time that Prx-2 is unregulated during the muscle differentiation and regeneration.
  
  
  CONCLUSIONS
  Prx-2 is upregulated via the PI3K/NF-κB pathway and attenuates oxidative stress during muscle differentiation and regeneration.
authors: Department of Biochemistry and Molecular Biology (BK21 project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Hyeran
authors: H
authors: Won
authors: Sangbin
authors: S
authors: Lim
authors: Miran
authors: M
authors: Jang
authors: Yeonghwan
authors: Y
authors: Kim
authors: Md Abdur
authors: MA
authors: Rashid
authors: K R
authors: KR
authors: Jyothi
authors: Amarjargal
authors: A
authors: Dashdorj
authors: Insug
authors: I
authors: Kang
authors: Joohun
authors: J
authors: Ha
authors: Sung Soo
authors: SS
authors: Kim
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000502:physiology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D018398:Homeodomain Proteins; D016328:NF-kappa B; C115469:Prrx2 protein, mouse; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D000111:Acetylcysteine