Induction of the paraoxonase-1 gene expression by resveratrol
Induction of the paraoxonase-1 gene expression by resveratrol
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DOI：
10.1161/01.atv.0000146530.24736.ce
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发表时间：
2004-12-01
影响因子：
8.7
通讯作者：
Morel, Y
中科院分区：
文献类型：
--
作者：
Gouédard, C;Barouki, R;Morel, Y
目的 - 人对氧磷酶-1 (PON-1) 是一种高密度脂蛋白相关酶，主要由肝脏分泌，对心血管疾病和有机磷中毒具有保护作用。白藜芦醇是一种多酚植物抗毒素，存在于葡萄和葡萄酒中，被认为具有心脏保护作用。它能够与雌激素受体α（ERα）等转录调节剂相互作用。我们研究了白藜芦醇对 PON-1 基因表达的影响。方法和结果 - PON-1 活性测定、Northern 印迹和转染实验表明，白藜芦醇增加了人肝细胞原代培养物和涉及转录机制的 HuH7 肝癌细胞系中的 PON-1 基因表达。白藜芦醇的作用不依赖于 ERα，令人惊讶的是，它是由芳基烃受体 (AhR) 和 PON-1 基因启动子中的非常规 AhR 响应元件介导的。白藜芦醇的这种激动作用对该 DNA 基序具有特异性，并且在经典 AhR 反应元件上未观察到。结论 - 这些观察结果表明 PON-1 基因诱导可能与白藜芦醇的心脏保护特性有关。他们还强调了 AhR 敏感基因的配体依赖性差异调节。
Objective - The human paraoxonase-1 (PON-1) is a high-density lipoprotein-associated enzyme, mainly secreted by the liver, that displays protective properties toward cardiovascular disease and organophosphate intoxication. Resveratrol is a polyphenolic phytoalexin found in grapes and wine and is thought to display cardioprotective effects. It is able to interact with transcriptional modulators such as the estrogen receptor alpha (ERalpha). We investigated the effect of resveratrol on the PON-1 gene expression.Methods and Results - PON-1 activity assays, Northern blot, and transfection experiments showed that resveratrol increased the PON-1 gene expression in human hepatocyte primary cultures and in the HuH7 hepatoma cell line involving a transcriptional mechanism. The resveratrol effect was not ERalpha-dependent and was surprisingly mediated by the aryl hydrocarbon receptor (AhR) and an unconventional AhR responsive element in the PON-1 gene promoter. This agonist effect of resveratrol was specific for this DNA motif and was not observed on classical AhR responsive elements.Conclusions - These observations suggest that the PON-1 gene induction may be involved in the cardioprotective properties of resveratrol. They also highlight a ligand-dependent differential modulation of AhR-sensitive genes.