HDACs and the senescent phenotype of WI-38 cells
HDACs and the senescent phenotype of WI-38 cells
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DOI：
10.1186/1471-2121-6-37
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发表时间：
2005-10-26
期刊：
影响因子：
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通讯作者：
Giardina, C
中科院分区：
文献类型：
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作者：
Place, RF;Noonan, EJ;Giardina, C
背景：正常细胞的增殖寿命有限，此后它们进入不可逆的生长停滞状态。这一过程被称为复制衰老，伴随着基因表达的变化，从而产生各种与衰老相关的表型。有人认为这些基因表达变化部分是由于组蛋白乙酰化机制的改变造成的。在这里，我们检查 HDAC 抑制剂对衰老前和衰老后 WI-38 细胞中衰老标志物表达的影响。结果：用 HDAC 抑制剂丁酸盐或曲古抑菌素 A (TSA) 处理衰老前和衰老后 WI-38 细胞。 HDAC抑制剂治疗后，衰老前期细胞p21（WAF1）和β-半乳糖苷酶表达增加，呈现扁平的衰老相关形态，并维持较低水平的蛋白酶体活性。这些改变也发生在 WI-38 细胞的正常复制衰老过程中，但 HDAC 抑制剂并未进一步加剧这些改变。我们还发现 HDAC1 水平在正常复制衰老过程中下降。结论：我们的研究结果表明 HDAC 影响与细胞衰老相关的许多表型变化。衰老细胞中 HDAC1 表达水平降低可能是介导向衰老表型转变的重要事件。
Background: Normal cells possess a limited proliferative life span after which they enter a state of irreversible growth arrest. This process, known as replicative senescence, is accompanied by changes in gene expression that give rise to a variety of senescence-associated phenotypes. It has been suggested that these gene expression changes result in part from alterations in the histone acetylation machinery. Here we examine the influence of HDAC inhibitors on the expression of senescent markers in pre- and post-senescent WI-38 cells.Results: Pre- and post-senescent WI-38 cells were treated with the HDAC inhibitors butyrate or trichostatin A (TSA). Following HDAC inhibitor treatment, pre- senescent cells increased p21(WAF1) and beta-galactosidase expression, assumed a flattened senescence-associated morphology, and maintained a lower level of proteasome activity. These alterations also occurred during normal replicative senescence of WI-38 cells, but were not accentuated further by HDAC inhibitors. We also found that HDAC1 levels decline during normal replicative senescence.Conclusion: Our findings indicate that HDACs impact numerous phenotypic changes associated with cellular senescence. Reduced HDAC1 expression levels in senescent cells may be an important event in mediating the transition to a senescent phenotype.