Downregulation of caveolin-1 affects bleomycin-induced growth arrest and cellular senescence in A549 cells
Downregulation of caveolin-1 affects bleomycin-induced growth arrest and cellular senescence in A549 cells
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DOI：
10.1016/j.biocel.2007.05.018
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Barth, Kathrin
中科院分区：
文献类型：
--
作者：
Linge, Annett;Weinhold, Karina;Barth, Kathrin
博来霉素是一种抗癌药物，可诱导细胞凋亡和衰老，这两个过程被认为涉及小窝蛋白-1。在这里，我们研究小窝蛋白-1在博来霉素诱导的衰老中的作用。我们发现博来霉素处理的A549细胞表现出：衰老样细胞形态;衰老相关的SA-β-半乳糖苷酶活性增加;细胞周期停滞;以及p53和p21的上调。正如预测的那样，我们发现小窝蛋白-1的量响应于博来霉素治疗而增加，并且小窝蛋白-1的调节影响p21和p53水平、细胞周期和衰老（SA-β-半乳糖苷酶活性）。有趣的是，当在博来霉素处理之前应用对小窝蛋白-I特异性的短发夹RNA时，在年轻的A549细胞中通过p53和p21和SA-β-半乳糖苷酶活性的衰老相关的细胞周期停滞减少。我们的研究结果支持下调小窝蛋白-I表达影响博来霉素诱导的细胞周期停滞和随后的细胞衰老是由p53和p21驱动的假设。16 k，（c）2007由Elsevier Ltd.出版
Bleomycin is an anti-cancer drug that induces both apoptosis and senescence, two processes thought to involve caveolin-1. Here we investigate the role of caveolin-1 in bleomycin-induced senescence. We show that bleomycin-treated A549 cells exhibit: senescence-like cell morphology; a senescence-associated increase in SA-beta-galactosidase activity; cell cycle arrest; and upregulation of p53 and p21. As predicted, we find that caveolin-1 amount increases in response to bleomycin-treatment and that modulation of caveolin-1 affects p21 and p53 levels, cell cycling, and senescence (SA-beta-galactosidase activity). Interestingly, senescence-associated cell cycle arrest via p53 and p21 and SA-beta-galactosidase activity is reduced in young A549 cells when short hairpin RNA specific for caveolin-I was applied before bleomycin-treatment. Our results support the hypothesis that down regulation of caveolin-I expression affects bleomycin-induced cell cycle arrest and subsequent cellular senescence that is driven by p53 and p21. 16k, (c) 2007 Published by Elsevier Ltd.