p53 and ATF-2 partly mediate the overexpression of COX-2 in H2 O2-induced premature senescence of human fibroblasts

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Abstract

Cyclooxygenase-2 and release of prostaglandin E2 are up-regulated in replicative senescence of dermal and prostate fibroblasts and in H2O2-induced premature senescence of IMR-90 lung fibroblasts expressing the catalytic subunit of telomerase. Inhibition of cyclooxygenase-2 activity by specific chemical inhibitor or siRNA attenuates the H2O2-induced increase of senescence associated β-galactosidase positive cells and attenuates growth arrest. In this work, p38MAPK activation and increased DNA binding activities of ATF-2 and p53 are shown to mediate cyclooxygenase-2 overexpression in premature senescence.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalBiogerontology
Volume10
Issue number3
DOIs
Publication statusPublished - 1 Jan 2009

Keywords

  • ATF-2
  • COX-2
  • Hydrogen peroxide
  • p38
  • p53
  • Senescence

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