TY - JOUR
T1 - Normal or stress-induced fibroblast senescence involves COX-2 activity
AU - Zdanov, S.
AU - Debacq-Chainiaux, Florence
AU - Toussaint, Olivier
AU - Bernard, D.
AU - Martien, S.
AU - Gosselin, K.
AU - Vercamer, C.
AU - Chelli, F.
AU - Abbadie, C.
PY - 2007/8/15
Y1 - 2007/8/15
N2 - 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 (PGE) 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 production are also increased about 10-fold during both NF-κB- or HO-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.
AB - 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 (PGE) 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 production are also increased about 10-fold during both NF-κB- or HO-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.
UR - http://www.scopus.com/inward/record.url?scp=34547230349&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2007.04.033
DO - 10.1016/j.yexcr.2007.04.033
M3 - Article
AN - SCOPUS:34547230349
SN - 0014-4827
VL - 313
SP - 3046
EP - 3056
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 14
ER -