The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties
The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties
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DOI：
10.1073/pnas.96.16.8867
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发表时间：
1999-08-03
影响因子：
11.1
通讯作者：
Behl, C
中科院分区：
文献类型：
--
作者：
Moosmann, B;Behl, C
在甾体分子家族中，只有雌激素具有防止氧化负担增加引起的神经元细胞死亡的能力。通过神经细胞系、脑膜和低密度脂蛋白氧化实验，我们发现雌激素的抗氧化和神经保护作用不依赖于它们作为激素的基因组特性，而是依赖于它们作为疏水酚分子的基本化学特性。17 β -雌二醇浓度在0.1-500 nM，分别赋予体外最大的雌激素受体依赖基因转录和最大的雌激素受体结合。不显示抗氧化或神经保护作用。相反，酚类化合物如2,4,6-三甲基苯酚、n -乙酰- 5-羟色胺和5-羟基吲哚具有神经保护作用，但没有任何雌激素性。比较各种天然和合成的单酚类和多酚类化合物，发现它们的抗氧化细胞保护作用与其雌激素活性之间没有相关性。这些结果对雌激素和酚类化合物的预期药理作用及其对雌激素受体依赖途径的影响之间的普遍相关性提出了质疑。此外，它们可能为减少激素副作用的神经保护抗氧化剂的合理设计打开了大门。
Among the family of steroidal molecules, only estrogens have the capability of preventing neuronal cell death caused by increased oxidative burden. Employing neuronal cell lines, brain membrane, and low density lipoprotein oxidation assays, we show that the antioxidant and neuroprotective effects of estrogens are dependent not on their genomic properties as hormones but rather on their basic chemical properties as hydrophobic phenolic molecules, Concentrations of 17 beta-estradiol of 0.1-500 nM, which confer maximum estrogen receptor-dependent gene transcription in vitro as well as maximum estrogen receptor binding, respectively, do not show antioxidant or neuroprotective effects. In contrast, phenolic compounds such as 2,4,6-trimethylphenol, N-acetylserotonin, and 5-hydroxyindole exhibit neuroprotective effects without any estrogenicity. Comparing various natural and synthetic mono- and polyphenolic compounds, no correlation between their antioxidant cytoprotective effect and their estrogenic potency can be seen. These results call into question the idea of a general correlation between the intended pharmacological effects of estrogens and phenolic compounds and their effect on estrogen receptor-dependent pathways. Furthermore, they may open the door toward the rational design of neuroprotective antioxidants with decreased hormonal side effects.