Role of p38MAPK and oxidative stress in copper-induced senescence

E. Boilan, V. Winant, E. Dumortier, J.-P. Piret, François Bonfitto, H.D. Osiewacz, F. Debacq-Chainiaux, O. Toussaint

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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 colocalized 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 foundthat Nrf2 transcription factor was activated and regulated the expression of genes involved in antioxidantresponse while p38MAPK regulated the appearance of premature senescence.

Original languageEnglish
Pages (from-to)2255-71
Number of pages17
JournalAge
Volume35
Issue number6
DOIs
Publication statusPublished - 2013

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Keywords

  • Aging
  • Copper
  • Human fibroblasts
  • Metals
  • Oxidative stress
  • P38
  • Senescence

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