Normal or stress-induced fibroblast senescence involves COX-2 activity

• Published in: Experimental cell research Vol. 313; no. 14; pp. 3046 - 3056
• Main Authors: Zdanov, Stéphanie, Bernard, David, Debacq-Chainiaux, Florence, Martien, Sébastien, Gosselin, Karo, Vercamer, Chantal, Chelli, Fazia, Toussaint, Olivier, Abbadie, Corinne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.2007; Elsevier BV; Elsevier
• Subjects: Animals; Cells, Cultured; Cellular biology; Cellular Senescence - physiology; Cyclooxygenase; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - metabolism; Dinoprostone - metabolism; Fibroblasts - cytology; Fibroblasts - physiology; Gene expression; Gene Silencing; Humans; Hydrogen Peroxide - metabolism; Inhibitor drugs; Life Sciences; Molecular biology; NF-kappa B - metabolism; NF-κB; Nitrobenzenes - metabolism; Oxidants - metabolism; Oxidative Stress; Prostaglandins; Proto-Oncogene Proteins c-rel - genetics; Proto-Oncogene Proteins c-rel - metabolism; Senescence; Sulfonamides - metabolism; Oxidative stress; NF-κB; Cyclooxygenase; Prostaglandins; Senescence
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2007.04.033

Cyclooxygenase-2 (COX-2) is an inducible enzyme of the prostaglandin biosynthesis pathway . It is involved in many stress responses, and its activity can produce oxidative damage, suggesting it could participate in senescence. In this study, COX-2 expression is shown to increase during senescence of normal human dermal or prostatic fibroblasts, and the ensuing prostaglandin E 2 (PGE 2) production to increase about 10-fold. Enhancing this COX-2 activity by supplying exogenous arachidonic acid accelerates the occurrence of the major markers of senescence, cell-size increase, spreading, senescence-associated-β-galactosidase (SA-β-Gal) activity and growth plateau. Conversely, blocking this COX-2 activity with the specific inhibitor NS398 partially inhibited the occurrence of these markers. COX-2 expression and PGE 2 production are also increased about 10-fold during both NF-κB- or H 2O 2-induced senescence. Using NS398 or small interferent RNA specifically targeting COX-2 attenuated the appearance of the SA-β-Gal activity and growth arrest in both stress situations. Taken together, these findings indicate that COX-2 is highly up-regulated during both normal and stress-induced fibroblast senescence and contributes to the establishment of the senescent characteristics.