title: Combinatorial effects of continuous protein synthesis, ERK-signaling, and reactive oxygen species on induction of cellular senescence.
abstract: Mammalian cells, when treated with sub-lethal doses of genotoxic stresses, slow down DNA synthesis but continue protein synthesis. Thus, these cells show an accumulation of proteins and undergo unbalanced growth. In the previous studies, we have shown that HeLa cells treated with excess thymidine or camptothecin undergo unbalanced growth, and prolonged unbalanced growth causes induction of cellular senescence, which is suppressed by restriction of protein synthesis or inhibition of ERK-signaling. In this study, we found that restriction of protein synthesis, inhibition of ERK-signaling, and elimination of reactive oxygen species showed a combinatorial effect on suppression of cellular senescence induced by excess thymidine or camptothecin. Of these, restriction of protein synthesis most effectively suppressed cellular senescence. Importantly, a similar combinatorial effect was observed in replicative senescence in normal human diploid fibroblasts. Our findings suggested that various stresses were cumulatively involved in cellular senescence, and suppression of cellular senescence was improved by combining the treatments that reduce the stresses.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takauji
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan.
authors.forename: Atsuki
authors.initials: A
authors.lastname: En
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan; Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama, Kanagawa 231-0048, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan; Ichiban Life Corporation, 1-1-7 Horai-cho, Naka-ku, Yokohama, Kanagawa 231-0048, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, Kanagawa 236-0027, Japan. Electronic address: mifuji@yokohama-cu.ac.jp.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013936:Thymidine / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002070:Butadienes; D009570:Nitriles; D017382:Reactive Oxygen Species; C113580:U 0126; D003513:Cycloheximide; D013936:Thymidine; D002166:Camptothecin
keywords: ERK; Protein synthesis; ROS; Senescence; Unbalanced growth