title: Altered acetylation of proteins in patients with rheumatoid arthritis revealed by acetyl-proteomics.
abstract: OBJECTIVE
  Post-translational modifications (PTMs) are often critical for the function of proteins as well as antigenicity of proteins. We here tried to elucidate alteration of PTMs in Rheumatoid arthritis (RA), focusing on acetylation. We applied acetyl-proteomics to peripheral blood mononuclear cells (PBMCs) to elucidate PTM difference between patients with RA and healthy donors.
  
  
  METHODS
  Proteins, extracted from peripheral blood mononuclear cells (PBMCs) of 7 RA patients and 7 healthy donors, were separated by 2-dimansional electrophoresis. Acetylation ratios of each protein spot were estimated by the combination of Sypro Ruby staining and anti-acetylated lysine antibodies. Proteins highly acetylated in the RA group were identified by mass spectrometry. Focusing on α-enolase (ENO1), one of the identified proteins, involvement of histone deacetylases (HDACs) in the high acetylation was investigated. Furthermore, the effects of acetylation on the activity of ENO1 were investigated.
  
  
  RESULTS
  In PBMCs from the patients with RA, 29 acetylated protein spots were detected. One of highly acetylated proteins in the RA patients was identified as ENO1. The acetylation of ENO1 was found to be regulated in part by HDAC1. The enzymatic activity of ENO1 was up-regulated by acetylation.
  
  
  CONCLUSIONS
  Highly acetylated ENO1 may play roles in the pathophysiology of RA through the maintenance of activated lymphocytes by increasing glycolysis-derived energy supply.
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Arito
authors.affiliation: Department of Genetic Engineering, Kinki University, Wakayama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ooka
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takakuwa
authors.affiliation: Disease Biomarker Analysis and Molecular Regulation, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: M S
authors.initials: MS
authors.lastname: Kurokawa
authors.affiliation: Department of Neurosurgery, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sase
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Suematsu
authors.affiliation: Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kanagawa, Japan. t3kato@marianna-u.ac.jp.
authors.forename: T
authors.initials: T
authors.lastname: Kato
mesh_terms: D000107:Acetylation; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004734:Energy Metabolism; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase