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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nitric oxide-induced cellular stress and p53 activation in chronic inflammation
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Nitric oxide-induced cellular stress and p53 activation in chronic inflammation

机译:一氧化氮诱导的细胞应激和p53在慢性炎症中的激活

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Free radical-induced cellular stress contributes to cancer during chronic inflammation. Here, we investigated mechanisms of p53 activation by the free radical, NO. NO from donor drugs induced both ataxia-telangiectasia mutated (ATM)- and ataxia-telangiectasia mutated and Rad3-related-dependent p53 posttranslational modifications, leading to an increase in p53 transcriptional targets and a G(2)/M cell cycle checkpoint. Such modifications were also identified in cells cocultured with NO-releasing macrophages. In noncancerous colon tissues from patients with ulcerative colitis (a cancer-prone chronic inflammatory disease), inducible NO synthase protein levels were positively correlated with p53 serine 15 phosphorylation levels. Immunostaining of HDM-2 and p21(WAF1) was consistent with transcriptionally active p53. Our study highlights a pivotal role of NO in the induction of cellular stress and the activation of a p53 response pathway during chronic inflammation. [References: 47]
机译:自由基引起的细胞应激在慢性炎症期间导致癌症。在这里,我们研究了自由基NO激活p53的机制。来自供体药物的NO诱导共济失调-毛细血管扩张突变(ATM)和共济失调-毛细血管扩张突变以及Rad3相关的p53翻译后修饰,导致p53转录靶点和G(2)/ M细胞周期检查点的增加。在与释放NO的巨噬细胞共培养的细胞中也鉴定出这种修饰。在溃疡性结肠炎(一种易患癌症的慢性炎症性疾病)患者的非癌性结肠组织中,诱导型NO合酶蛋白水平与p53丝氨酸15磷酸化水平呈正相关。 HDM-2和p21(WAF1)的免疫染色与转录活性p53一致。我们的研究突出了NO在慢性炎症过程中诱导细胞应激和激活p53反应途径中的关键作用。 [参考:47]

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