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p53 and ATF-2 partly mediate the overexpression of COX-2 in H2O2-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.

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Abbreviations

ATF-2:

Activating transcription factor-2

COX-2:

Cyclooxygenase 2

FCS:

Fetal calf serum

HDFs:

Human diploid fibroblasts

MAPK:

Mitogen activated protein kinase

NF-kB:

Nuclear factor-kappa B

PG:

Prostaglandin

RT-PCR:

Reverse transcription polymerase chain reaction

SA β-gal:

Senescence associated β-galactosidase

SIPS:

Stress induced premature senescence

siRNA:

Small interferent RNA

SD:

Standard deviation

TGF-beta1:

Transforming growth factor-beta1

TNF:

Tumor necrosis factor

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Acknowledgments

O. Toussaint and F. Debacq-Chainiaux are, respectively research associate and post-doctoral researcher of the FNRS, Belgium. S. Zdanov was a recipient of the FRIA, Belgium. We acknowledge the Région Wallonne (FSE First-DEI project “Cosmet-X”, Réseaux II, “Senegene” project, & “Nanotoxico project”) and the European Commission («Geha»Integrated Project (LSHM-CT-2004-503270);«Link-Age»Coordination Action (LSHM-CT-2005-523866);«Proteomage»Integrated Project (LSHM-CT-2005-518230);«Markage»Large Scale Integrating Project (HEALTH-F4-2008-200880) &«Matiss»Marie Curie Project (MTKI-CT-2006-042768)).

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  1. Research Unit on Cellular Biology (URBC), University of Namur (FUNDP), Rue de Bruxelles, 61, 5000, Namur, Belgium

    Stéphanie Zdanov, Olivier Toussaint & Florence Debacq-Chainiaux

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  1. Stéphanie Zdanov
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  2. Olivier Toussaint
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  3. Florence Debacq-Chainiaux
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Correspondence to Florence Debacq-Chainiaux.

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Zdanov, S., Toussaint, O. & Debacq-Chainiaux, F. p53 and ATF-2 partly mediate the overexpression of COX-2 in H2O2-induced premature senescence of human fibroblasts. Biogerontology 10, 291–298 (2009). https://doi.org/10.1007/s10522-008-9204-0

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