Zdanov Stéphanie, Toussaint Olivier, Debacq-Chainiaux Florence
University of Namur, Rue de Bruxelles, 61, 5000, Namur, Belgium.
Biogerontology. 2009 Jun;10(3):291-8. doi: 10.1007/s10522-008-9204-0. Epub 2008 Dec 11.
Cyclooxygenase-2 and release of prostaglandin E2 are up-regulated in replicative senescence of dermal and prostate fibroblasts and in H(2)O(2)-induced premature senescence of IMR-90 lung fibroblasts expressing the catalytic subunit of telomerase. Inhibition of cyclooxygenase-2 activity by specific chemical inhibitor or siRNA attenuates the H(2)O(2)-induced increase of senescence associated beta-galactosidase positive cells and attenuates growth arrest. In this work, p38(MAPK) activation and increased DNA binding activities of ATF-2 and p53 are shown to mediate cyclooxygenase-2 overexpression in premature senescence.
在真皮和前列腺成纤维细胞的复制性衰老以及表达端粒酶催化亚基的IMR - 90肺成纤维细胞的H₂O₂诱导的早衰中，环氧合酶 - 2和前列腺素E₂的释放上调。用特异性化学抑制剂或小干扰RNA抑制环氧合酶 - 2活性可减弱H₂O₂诱导的衰老相关β - 半乳糖苷酶阳性细胞的增加，并减弱生长停滞。在这项研究中，p38丝裂原活化蛋白激酶（p38(MAPK)）的激活以及活化转录因子2（ATF - 2）和p53的DNA结合活性增加被证明介导了早衰中环氧合酶 - 2的过表达。
