Hdm2 Nuclear Foci 形成與細胞老化關係之探討
The Role of Hdm2 Nuclear Foci Formation in Cellular Senescence
Date Issued
2006
Date
2006
Author(s)
Shih, Ya-Hsun
DOI
zh-TW
Abstract
Abstract
Cellular senescence is an irreversible and permanent phenomenon of cell cycle arrest. Consequently, cellular senescence as well as apoptosis is recognized as tumor suppressive mechanism. Based on different inducing mechanism, cellular senescence could divide into two groups as replicative senescence and premature senescence. From previous studies, sublethal H2O2 concentration treatment could induce senescence in WI38 cell, and Hdm2 form the nuclear foci in the H2O2-induced senescent cells. In this study, we attempt to investigate whether Hdm2 nuclear foci formation correlate with cellular senescence phenomenon. Besides two established premature senescence systems induced by AOA and H2O2, we set up another two different senescence systems to compare Hdm2 nuclear foci phenomenon between systems. Otherwise, we use various potential senescence-interfering drugs co-treat with H2O2 and observe whether these drugs could disturb cellular senescence and Hdm2 nuclear foci formation corresponsively. we categorize our findings into 3 major groups : First, using Sirt1 activator Resveratrol and Sirt1 inhibitor Nicotinamide, p38 inhibitor SB203580 and Erk inhibitor PD98059 individually co-treat with H2O2 fails to block H2O2-induced senescence and fails to affect Hdm2 nuclear foci formation. Second, using PI3K inhibitor wortmannin could block H2O2-induced senescence, but did not disturb Hdm2 nuclear foci status. Finally, we found HDAC inhibitor TSA co-treat with H2O2 could destroy Hdm2 nuclear foci formation and lower cellular senescence ratio. This finding implies there might be some correlations between Hdm2 nuclear foci formation and cellular senescence phenomenon.
Subjects
細胞老化
過氧化氫
細胞核內聚集現象
cellular senescence
H2O2
Nuclear foci
Type
other
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