کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2552277 1560743 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparison of global DNA methylation profiles in replicative versus premature senescence
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Comparison of global DNA methylation profiles in replicative versus premature senescence
چکیده انگلیسی

DNA methylation is considered to play an essential role in cellular senescence. To uncover the mechanism underlying cellular senescence, we established the model of premature senescence induced by hydrogen peroxide (H2O2) in human embryonic lung fibroblasts and investigated the changes of genome methylation, DNA methyltransferases (DNMTs) and DNA-binding domain proteins (MBDs) in comparison with those observed during normal replicative senescence. We found that premature senescence triggered by H2O2 exhibited distinct morphological characteristics and proliferative capacity which were similar to those of replicative senescence. The genome methylation level decreased gradually during the premature as well as replicative senescence, which was associated with the reduction in the expression of DNMT1, reflecting global hypomethylation as a distinct feature of senescent cells. The levels of DNMT3b and methyl-CpG binding protein 2 (MeCP2) increased in both mid-aged and replicative senescent cells, while DNMT3a and MBD2 were upregulated in the mid-aged cells. Only DNMT3b was elevated in the cells in the premature senescence persistence status. Additionally, the expression for DNMTs, MBD2 and MeCP2 was increased rapidly upon H2O2 treatment. These results indicate that H2O2-induced premature senescence share some features of replicative senescence, such as basic biological characteristics and global hypomethylation while there are slight differences in the profile of methylation-associated enzyme expression. Oxidative damage may hence be a causative factor in epigenetic alteration partly responsible for cellular senescence.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 83, Issues 13–14, 26 September 2008, Pages 475–480
نویسندگان
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