title: DJ-1 protects against undernutrition-induced atrophy through inhibition of the MAPK-ubiquitin ligase pathway in myoblasts.
abstract: OBJECTIVE
  The purpose of this study is to explore whether antioxidant DJ-1 protein affects the atrophy of skeletal muscle cell induced by undernutrition.
  
  
  METHODS
  To determine cell atrophic responses, L6 cell line and skeletal primary cells from mouse hind limbs were cultivated under condition of FBS-free and low glucose. Changes of protein expression were analyzed using Western blot. Overexpression and knockdown of DJ-1 was performed in cells to assess its influence on cell atrophic responses.
  
  
  RESULTS
  Undernutrition decreased cell size and increased the abundance of oxidized form and total form of DJ-1 protein in L6 myoblasts. The undernourished cells revealed an elevation in the expression of muscle-specific RING finger-1 (MuRF-1) and atrogin-1, and in the phosphorylations of p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase/c-Jun N-terminal kinase compared with control groups. Moreover, DJ-1-knockout mice showed a decrease in cell size and an enhancement in the expression of MuRF-1 and atrogin-1, as well as in the phosphorylation of MAPKs in gastrocnemius muscles; these changes were also observed in L6 cells transfected with siRNA of DJ-1. On the other hand, L6 cells overexpressing full-length DJ-1 did not exhibit the alterations in cell size and ubiquitin ligases seen after undernourished states of control cells. Myotubes differentiated from L6 cells also showed elevated expression of MuRF-1 and atrogin-1 in response to undernutrition.
  
  
  CONCLUSIONS
  These results suggest that DJ-1 protein may contribute to undernutrition-induced atrophy via MAPKs/ubiquitin ligase pathway in skeletal muscle cells.
authors.affiliation: Department of Physical Therapy, College of Public Health & Welfare, Yongin University, Yongin-city 449-714, South Korea.
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medicine, Konkuk University School of Medicine, Chungju-city 380-701, South Korea.
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.affiliation: Department of Medicine, Konkuk University School of Medicine, Chungju-city 380-701, South Korea.
authors.forename: Seung Hyo
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Medicine, Konkuk University School of Medicine, Chungju-city 380-701, South Korea.
authors.forename: Kang-Pa
authors.initials: KP
authors.lastname: Lee
authors.affiliation: Laboratory Animal Resources Division, National Institute of Food and Drug Safety Evaluation, Korea Food & Drug Administration, Cheongwon-gun 363-700, South Korea.
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.affiliation: Department of Physical Therapy, College of Public Health & Welfare, Yongin University, Yongin-city 449-714, South Korea.
authors.forename: Mee-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Department of Physical Therapy, College of Health Welfare, Wonkwang Health Science University, Iksan 570-750, South Korea.
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physical Therapy, College of Health Science, Honam University, Gwangju 506-714, South Korea.
authors.forename: Jeong-Uk
authors.initials: JU
authors.lastname: Lee
authors.affiliation: Department of Medicine, Konkuk University School of Medicine, Chungju-city 380-701, South Korea. Electronic address: bkkim2@kku.ac.kr.
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D001284:Atrophy / Q000201:enzymology / Q000517:prevention & control; D002460:Cell Line; D005260:Female; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D044342:Malnutrition / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D032446:Myoblasts / Q000201:enzymology* / Q000473:pathology; D015513:Oncogene Proteins / Q000172:deficiency*; D009924:Organ Culture Techniques; D054464:Peroxiredoxins / Q000172:deficiency*; D000071617:Protein Deglycase DJ-1; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D015513:Oncogene Proteins; D054464:Peroxiredoxins; D044767:Ubiquitin-Protein Ligases; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1
keywords: Atrogin-1; Atrophy; DJ-1; L6 cells; MuRF-1; Undernutrition