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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
Issue Date
2008-10-14
Publisher
Elsevier
Citation
Mech Ageing Dev. 129(12), 706-713
Keywords
Aspirin/pharmacologyCaveolin 1/metabolismCell Aging/*drug effects/*physiologyCells, CulturedCyclin-Dependent Kinase Inhibitor p21/metabolismCyclooxygenase 1/metabolismCyclooxygenase 2/*metabolismCyclooxygenase 2 Inhibitors/*pharmacologyCyclooxygenase Inhibitors/pharmacologyFibroblasts/cytology/drug effects/metabolismFlurbiprofen/pharmacologyHumansIbuprofen/pharmacologyKineticsModels, BiologicalNF-kappa B/metabolismNitrobenzenes/pharmacologyPyrazoles/pharmacologyReactive Oxygen Species/metabolismSkin/cytology/drug effects/metabolismSkin Aging/drug effects/physiologySulfonamides/pharmacologyTumor 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
DOI
https://doi.org/10.1016/j.mad.2008.09.003
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biochemistry & Molecular Biology (생화학교실)Journal Papers (저널논문_생화학교실)
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