title: Down-regulation of Ku autoantigen, DNA-dependent protein kinase, and poly(ADP-ribose) polymerase during cellular senescence.
abstract: During aging and cellular senescence mutations accumulate in genomic and mitochondrial DNA. Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase have an essential role in DNA damage recognition. Our purpose was to find out whether cellular senescence of fibroblasts affects the protein components that recognize DNA damage and induce the repair process. We compared presenescent and replicatively senescent human WI-38 fibroblasts with each other and with SV-40 immortalized and serum-deficient quiescent WI-38 cells. Our results showed that replicative senescence significantly decreased the nuclear level of both p70 and p86 components of Ku autoantigen. SV-40 immortalization and cellular quiescence did not affect the level of the p86 component but slightly increased that of p70. Both replicative senescence and cellular quiescence decreased the activity of DNA-dependent protein kinase in WI-38 fibroblasts. On the other hand, SV-40 immortalization increased the activity of DNA-dependent protein kinase. The protein level of poly(ADP-ribose) polymerase (PARP) was strongly decreased in replicatively senescent fibroblasts. Quiescence of early-passage fibroblasts also slightly reduced the protein level of PARP. Apoptosis was not observed in replicatively senescent fibroblasts. Our results show that replicative senescence and to some extent cellular quiescence down-regulate the recognition system of DNA damage involving Ku autoantigens, DNA-dependent protein kinase, and PARP and hence could enhance the accumulation of DNA damage during aging.
authors.affiliation: Department of Neuroscience and Neurology, University of Kuopio, Finland. antero.salminen@uku.fi
authors.forename: A
authors.initials: A
authors.lastname: Salminen
authors.forename: M
authors.initials: M
authors.lastname: Helenius
authors.forename: T
authors.initials: T
authors.lastname: Lahtinen
authors.forename: P
authors.initials: P
authors.lastname: Korhonen
authors.forename: T
authors.initials: T
authors.lastname: Tapiola
authors.forename: H
authors.initials: H
authors.lastname: Soininen
authors.forename: V
authors.initials: V
authors.lastname: Solovyan
mesh_terms: D000595:Amino Acid Sequence; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology; D053938:DNA Fragmentation; D004265:DNA Helicases; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005347:Fibroblasts; D006801:Humans; D000072200:Ku Autoantigen; D008168:Lung / Q000166:cytology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D034961:Antigens, Nuclear; D001324:Autoantigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011065:Poly(ADP-ribose) Polymerases; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen