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Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner

DC Field Value Language
dc.contributor.authorKim, So Ra-
dc.contributor.authorPark, Jung Hae-
dc.contributor.authorLee, Mi Eun-
dc.contributor.authorPark, Jeong Soo-
dc.contributor.authorPark, Sang Chul-
dc.contributor.authorHan, Jeong A-
dc.date.accessioned2010-06-07T01:31:05Z-
dc.date.available2010-06-07T01:31:05Z-
dc.date.issued2008-10-14-
dc.identifier.citationMech Ageing Dev. 129(12), 706-713en
dc.identifier.issn0047-6374 (Print)-
dc.identifier.urihttp://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-
dc.identifier.urihttps://hdl.handle.net/10371/67492-
dc.description.abstractIt 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.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAspirin/pharmacologyen
dc.subjectCaveolin 1/metabolismen
dc.subjectCell Aging/*drug effects/*physiologyen
dc.subjectCells, Cultureden
dc.subjectCyclin-Dependent Kinase Inhibitor p21/metabolismen
dc.subjectCyclooxygenase 1/metabolismen
dc.subjectCyclooxygenase 2/*metabolismen
dc.subjectCyclooxygenase 2 Inhibitors/*pharmacologyen
dc.subjectCyclooxygenase Inhibitors/pharmacologyen
dc.subjectFibroblasts/cytology/drug effects/metabolismen
dc.subjectFlurbiprofen/pharmacologyen
dc.subjectHumansen
dc.subjectIbuprofen/pharmacologyen
dc.subjectKineticsen
dc.subjectModels, Biologicalen
dc.subjectNF-kappa B/metabolismen
dc.subjectNitrobenzenes/pharmacologyen
dc.subjectPyrazoles/pharmacologyen
dc.subjectReactive Oxygen Species/metabolismen
dc.subjectSkin/cytology/drug effects/metabolismen
dc.subjectSkin Aging/drug effects/physiologyen
dc.subjectSulfonamides/pharmacologyen
dc.subjectTumor Suppressor Protein p53/metabolismen
dc.titleSelective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manneren
dc.typeArticleen
dc.contributor.AlternativeAuthor김소라-
dc.contributor.AlternativeAuthor박정희-
dc.contributor.AlternativeAuthor이미은-
dc.contributor.AlternativeAuthor박정수-
dc.contributor.AlternativeAuthor박상철-
dc.contributor.AlternativeAuthor한정아-
dc.identifier.doi10.1016/j.mad.2008.09.003-
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