title: Senescence-Associated Changes in Proteome and O-GlcNAcylation Pattern in Human Peritoneal Mesothelial Cells.
abstract: BACKGROUND
  Senescence of peritoneal mesothelial cells represents a biological program defined by arrested cell growth and altered cell secretory phenotype with potential impact in peritoneal dialysis. This study aims to characterize cellular senescence at the level of global protein expression profiles and modification of proteins with O-linked N-acetylglucosamine (O-GlcNAcylation).
  
  
  METHODS
  A comparative proteomics analysis between young and senescent human peritoneal mesothelial cells (HPMC) was performed using two-dimensional gel electrophoresis. O-GlcNAc status was assessed by Western blot under normal conditions and after modulation with 6-diazo-5-oxo-L-norleucine (DON) to decrease O-GlcNAcylation or O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino N-phenyl carbamate (PUGNAc) to increase O-GlcNAcylation.
  
  
  RESULTS
  Comparison of protein pattern of senescent and young HPMC revealed 29 differentially abundant protein spots, 11 of which were identified to be actin (cytoplasmic 1 and 2), cytokeratin-7, cofilin-2, transgelin-2, Hsp60, Hsc70, proteasome β-subunits (type-2 and type-3), nucleoside diphosphate kinase A, and cytosolic 5'(3')-deoxyribonucleotidase. Although the global level of O-GlcNAcylation was comparable, senescent cells were not sensitive to modulation by PUGNAc.
  
  
  CONCLUSIONS
  This study identified changes of the proteome and altered dynamics of O-GlcNAc regulation in senescent mesothelial cells. Whereas changes in cytoskeleton-associated proteins likely reflect altered cell morphology, changes in chaperoning and housekeeping proteins may have functional impact on cellular stress response in peritoneal dialysis.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Zytoprotec GmbH, 1090 Vienna, Austria.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Herzog
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tarantino
authors.affiliation: Department of Pathophysiology, University of Medical Sciences, 60-806 Poznan, Poland.
authors.forename: András
authors.initials: A
authors.lastname: Rudolf
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Aufricht
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria ; Zytoprotec GmbH, 1090 Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kratochwill
authors.affiliation: Department of Pathophysiology, University of Medical Sciences, 60-806 Poznan, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
mesh_terms: D000117:Acetylglucosamine / Q000235:genetics; D000215:Acylation / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D003599:Cytoskeleton / Q000235:genetics; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D010530:Peritoneal Dialysis; D014176:Protein Biosynthesis / Q000235:genetics*; D020543:Proteome / Q000235:genetics*; D040901:Proteomics; D059467:Transcriptome
chemical_list: D020543:Proteome; D017351:N-Acetylglucosaminyltransferases; D000117:Acetylglucosamine