title: Low-dose radiation differentially regulates protein acetylation and histone deacetylase expression in human coronary artery endothelial cells.
abstract: Ionizing radiation induces cardiovascular disease, the endothelium being the main target. The exact mechanism of the damage is unclear but the involvement of multiple signaling pathways is probable. Reversible lysine acetylation is a posttranslational protein modification that regulates activity across a broad range of signaling pathways. The aim of this study was to determine if a low radiation dose results in acetylome alteration in endothelial cells.
  
  
  
  Human coronary artery endothelial cell line was irradiated with Cs-137 gamma-rays (0.5 Gy) and proteomics analysis was performed using enriched acetylated peptides and all peptides. Data were validated using immunoblotting, deacetylase activity assay, and RhoA activity assay.
  
  
  
  Nearly a hundred proteins were found to have an altered acetylation status 24 h after irradiation, primarily due to an overall decrease in acetylation. The expression of specific deacetylases was significantly increased, coinciding with an enhancement in global deacetylase activity. Proteins changed in their acetylation status belonged to several pathways including protein synthesis, cytoskeleton-related processes, protein folding and calcium signaling. The predicted changes in the RhoA/actin cytoskeleton pathway were validated by immunoassay.
  
  
  
  This study shows that protein acetylation is an important mediator of radiation responses in human cardiac coronary endothelial cells. Increased knowledge of the endothelial response to radiation is crucial for the development of normal tissue-sparing modalities during radiation therapy.
authors.affiliation: a Institute of Radiation Biology, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Zarko
authors.initials: Z
authors.lastname: Barjaktarovic
authors.affiliation: b Research Unit Protein Science, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.affiliation: a Institute of Radiation Biology, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Omid
authors.initials: O
authors.lastname: Azimzadeh
authors.affiliation: a Institute of Radiation Biology, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.affiliation: c Biological Effects Department, Centre for Radiation , Chemicals and Environmental Hazards, Public Health England , Chilton , Oxfordshire , UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Raj
authors.affiliation: a Institute of Radiation Biology, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.|d Chair of Radiation Biology , Technical University Munich , Munich , Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: a Institute of Radiation Biology, Helmholtz Zentrum München , German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000107:Acetylation / Q000528:radiation effects; D002460:Cell Line; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000502:physiology* / Q000528:radiation effects*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology / Q000528:radiation effects; D006655:Histone Deacetylases / Q000096:biosynthesis*; D006801:Humans; D020543:Proteome / Q000096:biosynthesis*; D011829:Radiation Dosage
chemical_list: D020543:Proteome; D006655:Histone Deacetylases
keywords: Acetylation; cardiovascular disease; endothelial cell; ionizing radiation; proteomics; sirtuin