title: Molecular basis for premature senescence induced by surfactants in normal human cells.
abstract: Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluorescein-labeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.
authors.affiliation: a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Yamakami
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Yonekura
authors.forename: Ikuru
authors.initials: I
authors.lastname: Kudo
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
mesh_terms: D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology*; D019301:Oleic Acid / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction; D013501:Surface-Active Agents / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D007093:Imidazoles; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D013501:Surface-Active Agents; D019301:Oleic Acid; D011092:Polyethylene Glycols; D017830:Octoxynol; C010615:Nonidet P-40; D003513:Cycloheximide; D048051:p38 Mitogen-Activated Protein Kinases; D001616:beta-Galactosidase; C093642:SB 203580
keywords: cellular senescence; oleic acid; p38; surfactant; unbalanced growth