title: Role of p38MAPK and oxidative stress in copper-induced senescence.
abstract: In the present work, we indicate that copper is involved in the senescence of human diploid fibroblasts and we describe mechanisms to explain it. Using different techniques, we show for the first time an accumulation of copper in cells during replicative senescence. This accumulation seems to be co-localized with lipofuscin. Second, we observed that an incubation of cells with copper sulfate induced oxidative stress, antioxidant response and premature senescence. Antioxidant molecules reduced the appearance of premature senescence. Third, we found that Nrf2 transcription factor was activated and regulated the expression of genes involved in antioxidant response while p38(MAPK) regulated the appearance of premature senescence.
authors.affiliation: NARILIS URBC, University of Namur (FUNDP), 61, rue de Bruxelles, 5000, Namur, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Boilan
authors.forename: Virginie
authors.initials: V
authors.lastname: Winant
authors.forename: Elise
authors.initials: E
authors.lastname: Dumortier
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Piret
authors.forename: François
authors.initials: F
authors.lastname: Bonfitto
authors.forename: Heinz D
authors.initials: HD
authors.lastname: Osiewacz
authors.forename: Florence
authors.initials: F
authors.lastname: Debacq-Chainiaux
authors.forename: Olivier
authors.initials: O
authors.lastname: Toussaint
mesh_terms: D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D003300:Copper / Q000378:metabolism*; D019327:Copper Sulfate / Q000494:pharmacology*; D004171:Diploidy; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D008168:Lung / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D056928:X-Ray Absorption Spectroscopy; D048051:p38 Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D012313:RNA; D003300:Copper; D048051:p38 Mitogen-Activated Protein Kinases; D019327:Copper Sulfate