کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2131746 1086657 2007 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Normal or stress-induced fibroblast senescence involves COX-2 activity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Normal or stress-induced fibroblast senescence involves COX-2 activity
چکیده انگلیسی

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 E2 (PGE2) 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 PGE2 production are also increased about 10-fold during both NF-κB- or H2O2-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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 313, Issue 14, 15 August 2007, Pages 3046–3056
نویسندگان
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