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Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner
Cited 29 time in
Web of Science
Cited 29 time in Scopus
- Authors
- Issue Date
- 2008-10-14
- Publisher
- Elsevier
- Citation
- Mech Ageing Dev. 129(12), 706-713
- Keywords
- Aspirin/pharmacology ; Caveolin 1/metabolism ; Cell Aging/*drug effects/*physiology ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Cyclooxygenase 1/metabolism ; Cyclooxygenase 2/*metabolism ; Cyclooxygenase 2 Inhibitors/*pharmacology ; Cyclooxygenase Inhibitors/pharmacology ; Fibroblasts/cytology/drug effects/metabolism ; Flurbiprofen/pharmacology ; Humans ; Ibuprofen/pharmacology ; Kinetics ; Models, Biological ; NF-kappa B/metabolism ; Nitrobenzenes/pharmacology ; Pyrazoles/pharmacology ; Reactive Oxygen Species/metabolism ; Skin/cytology/drug effects/metabolism ; Skin Aging/drug effects/physiology ; Sulfonamides/pharmacology ; Tumor Suppressor Protein p53/metabolism
- Abstract
- It has been recently proposed that pro-inflammatory genes such as cyclooxygenase-2 (COX-2) play a key role in the aging process. However, it remains unclear whether the pro-inflammatory activity of COX-2 is involved in the aging process and whether COX-2 inhibitors prevent aging. We therefore examined the effect of COX-2 inhibitors on aging in the cellular senescence model of human dermal fibroblasts (HDFs). While the catalytic activity of COX-2 was observed to increase in the senescence process, we found that among three selective COX-2 inhibitors studied, only NS-398 inhibited the senescence whereas celecoxib and nimesulide accelerated the senescence. Non-selective COX inhibitors including aspirin, ibuprofen and flurbiprofen accelerated the senescence. The senescence-regulating effect of selective COX-2 inhibitors had no correlation with cellular reactive oxygen species levels, NF-kappaB activities or protein levels of p53 and p21. We instead found that selective COX-2 inhibitors regulate caveolin-1 expression at transcriptional levels, which was closely associated with the inhibitors' effect on the senescence. Collectively, these results suggest that COX-2 catalytic activity does not mediate HDF senescence and that selective COX-2 inhibitors modulate HDF senescence by a catalytic activity-independent mechanism.
- ISSN
- 0047-6374 (Print)
- Language
- English
- URI
- http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T31-4TGS7BY-1-F&_cdi=4933&_user=168665&_orig=search&_coverDate=12%2F31%2F2008&_sk=998709987&view=c&wchp=dGLbVzW-zSkzV&md5=60e04ee8973bd09337f434d54e4398b2&ie=/sdarticle.pdf
https://hdl.handle.net/10371/67492
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