title: N-methyl-D-aspartate (NMDA) impairs myogenesis in C2C12 cells.
abstract: N-methyl-d-aspartate (NMDA) is expressed in sensory neurons and plays important roles in peripheral pain mechanisms. The aim of this study was to examine the effects and molecular mechanisms of NMDA on C2C12 myoblast proliferation and differentiation.
  
  
  
  Cytotoxicity and differentiation were examined by the MTT assay, reverse transcription-polymerase chain reaction, and immunofluorescence.
  
  
  
  NMDA had no cytotoxicity (10-500 μM) and inhibited myoblastic differentiation of C2C12 cells, as assessed by F-actin immunofluorescence and levels of mRNAs encoding myogenic markers such as myogenin and myosin heavy-chain 2. It inhibited phosphorylation of mammalian target of rapamycin (mTOR) by inactivating mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. It induced reactive oxygen species production. Furthermore, NMDA-suppressed expression of F-actin was reversed by adding the antioxidant N-acetylcysteine.
  
  
  
  Collectively, these results indicate that NMDA impairs myogenesis or myogenic differentiation in C2C12 cells through the mTOR/MAPK signaling pathways and may lead to skeletal muscle degeneration. Muscle Nerve 56: 510-518, 2017.
authors.affiliation: Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Q-SChick
authors.initials: QS
authors.lastname: Auh
authors.affiliation: Department of Oral and Maxillofacial Pathology, MRC, School of Dentistry, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Kyung-Ran
authors.initials: KR
authors.lastname: Park
authors.affiliation: Department of Dentistry, Graduate School, Kyung Hee University, Seoul, Korea.
authors.forename: Myeong-Ok
authors.initials: MO
authors.lastname: Lee
authors.affiliation: Department of Dentistry, Graduate School, Kyung Hee University, Seoul, Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Hwang
authors.affiliation: Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Kang
authors.affiliation: Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Korea.
authors.forename: Jung-Pyo
authors.initials: JP
authors.lastname: Hong
authors.affiliation: Department of Oral and Maxillofacial Pathology, MRC, School of Dentistry, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Hyung-Mun
authors.initials: HM
authors.lastname: Yun
authors.affiliation: Department of Oral and Maxillofacial Pathology, MRC, School of Dentistry, Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea.
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D024510:Muscle Development / Q000187:drug effects* / Q000502:physiology; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism; D016202:N-Methylaspartate / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D016202:N-Methylaspartate
keywords: NMDA; ROS; differentiation; mTOR; myalgic disorder; myogenesis