p53 and ATF-2 partly mediate the overexpression of COX-2 in H(2)O (2)-induced premature senescence of human fibroblasts.
Cyclooxygenase-2 and release of prostaglandin E2 are up-regulated in replicative senescence of dermal and prostate fibroblasts and in H(2)O(2)-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 H(2)O(2)-induced increase of senescence associated beta-galactosidase positive cells and attenuates growth arrest. In this work, p38(MAPK) activation and increased DNA binding activities of ATF-2 and p53 are shown to mediate cyclooxygenase-2 overexpression in premature senescence.
Zdanov
Stéphanie
S
University of Namur, Rue de Bruxelles, 61, 5000, Namur, Belgium.
Toussaint
Olivier
O
Debacq-Chainiaux
Florence
F
D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048051:p38 Mitogen-Activated Protein Kinases; C509186:TERT protein, human; D019098:Telomerase