Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells
Nitric oxide impairs the 17β-estradiol-induced apoptosis in human colon adenocarcinoma cells
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DOI：
10.1677/erc.1.01106
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发表时间：
2006-06-01
影响因子：
3.9
通讯作者：
Ascenzi, P.
中科院分区：
文献类型：
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作者：
Marino, M.;Galluzzo, P.;Ascenzi, P.
一氧化氮 (NO) 和 17 β-雌二醇 (E2) 对于胃肠道健康和疾病都很重要。一氧化氮有助于胃肠道蠕动以及炎症和致癌过程。相比之下，E2 可使结肠腺瘤和结肠癌的发生率降低约 30%。我们报告了 E2-雌激素受体 (ER) P 诱导的人类结肠腺癌的基因组和非基因组效应。还评估了 NO 对 ER β 活性的影响。 E2-ER β依赖性基因转录受到外源NO的抑制，而一些对凋亡级联激活很重要的非基因组E2依赖性效应（例如p38/MAP激酶）不受NO影响。然而，NO 通过抑制 caspase-3 来损害 E2 诱导的人结肠腺癌细胞中的促凋亡级联反应。 NO 的影响可能反映了 ER beta 的 DNA 识别域以及 caspase-3 活性位点中存在的 Cys 残基的化学修饰。总体而言，高NO浓度抑制了E2在胃肠道中的保护作用，这表明在高氧化还原应激条件下，例如在慢性感染或病原体攻击引起的免疫系统特异性激活的情况下，半胱天冬酶依赖性细胞凋亡级联可能变得至关重要。
Nitric oxide (NO) and 17 beta-estradiol (E2) are both important in gastrointestinal health and disease. NO contributes to gastrointestinal motility as well as to inflammation and carcinogenic processes. By contrast, E2 reduces the incidence of colon adenoma and carcinoma by about 30%. We report the genomic and non-genomic E2-estrogen receptor (ER) P-induced effects in human colon adenocarcinoma. The effect of NO on ER beta activities was also assessed. The E2-ER beta-dependent gene transcription was inhibited by exogenous NO, whereas some non-genomic E2-dependent effects (e.g. p38/MAP kinase), important for the activation of the apoptotic cascade, were unaffected by NO. However, NO impaired the E2-induced pro-apoptotic cascade in human colon adenocarcinoma cells by inhibiting caspase-3. The effects of NO may reflect chemical modification(s) of Cys residues present in the DNA recognition domain of ER beta as well as in the caspase-3 active site. On the whole, high NO concentrations suppressed the E2 protective effects in the gastrointestinal tract, suggesting that the caspase-dependent apoptotic cascade may become critical under conditions of high redox stress such as occur under specific activation of the immune system by chronic infections or pathogen challenge.