Hypochlorous acid activates the tumor suppressor protein p53 in cultured human skin fibroblasts.
Hypochlorous acid activates the tumor suppressor protein p53 in cultured human skin fibroblasts.
复制标题
次氯酸可激活培养的人皮肤成纤维细胞中的肿瘤抑制蛋白 p53。
DOI：
--
复制
发表时间：
1998
影响因子：
3.9
通讯作者：
A. Kettle
中科院分区：
文献类型：
--
作者：
G. Vile;L. Rothwell;A. Kettle
与慢性炎症相关的致癌性归因于中性粒细胞及其产生的氧化剂。中性粒细胞在慢性炎症部位积聚，在那里它们被刺激产生过氧化氢，过氧化氢通过共释放的髓过氧化物酶转化为次氯酸。我们在此报道，在与受刺激的中性粒细胞一起孵育的培养的人皮肤成纤维细胞中，肿瘤抑制蛋白 p53 的水平有所增加。 p53 的增加需要髓过氧化物酶依赖性次氯酸的产生，并且可以通过将细胞暴露于纯化的髓过氧化物酶和过氧化氢生成系统产生的次氯酸流来模拟。 p53 水平对次氯酸非常敏感，每分钟低至 0.2 µM 的通量即可有效。当成纤维细胞用次氯酸处理时，p53 依赖性蛋白 WAF1/CIP1 的水平也升高。该结果表明用次氯酸处理的细胞中的p53具有转录活性。单独使用过氧化氢也会升高 p53 和 WAF1/CIP1，但所需的通量比对次氯酸有效的通量高出近 10 倍。我们的结果表明次氯酸参与中性粒细胞依赖性信号转导途径的启动，这可以最大限度地减少慢性炎症的致癌性。
The carcinogenicity associated with chronic inflammation has been attributed to neutrophils and the oxidants they produce. Neutrophils accumulate at sites of chronic inflammation, where they are stimulated to produce hydrogen peroxide which is converted to hypochlorous acid by coreleased myeloperoxidase. We report here that levels of the tumor suppressor protein p53 were increased in cultured human skin fibroblasts that had been incubated with stimulated neutrophils. The increase in p53 required the myeloperoxidase-dependent generation of hypochlorous acid and could be mimicked by exposing cells to a flux of hypochlorous acid produced by purified myeloperoxidase and a hydrogen peroxide-generating system. Levels of p53 were very sensitive to hypochlorous acid, with fluxes as low as 0.2 microM per min being effective. Levels of the p53-dependent protein WAF1/CIP1 were also elevated when fibroblasts were treated with hypochlorous acid. This result indicates that the p53 in the cells treated with hypochlorous acid was transcriptionally active. Hydrogen peroxide alone also elevated p53 and WAF1/CIP1, but the fluxes required were nearly 10-fold higher than those that were effective for hypochlorous acid. Our results implicate hypochlorous acid in the neutrophil-dependent initiation of a signal transduction pathway which could minimize the carcinogenicity of chronic inflammation.
登录
查看更多内容
影响因子：
2.9
作者：
Berleth, ES;Pickart, CM
通讯作者：
Pickart, CM
影响因子：
--
作者：
E. Thomas;M. Grisham;M. Jefferson
通讯作者：
E. Thomas;M. Grisham;M. Jefferson
影响因子：
15.9
作者：
SCHRAUFSTATTER, I;HYSLOP, PA;COCHRANE, CG
通讯作者：
COCHRANE, CG
影响因子：
20.3
作者：
S. Weitzman;L. Gordon
通讯作者：
S. Weitzman;L. Gordon
影响因子：
15.9
作者：
SCHRAUFSTATTER, IU;BROWNE, K;COCHRANE, CG
通讯作者：
COCHRANE, CG