Neuroprotection against oxidative stress by estrogens: Structure-activity relationship
Neuroprotection against oxidative stress by estrogens: Structure-activity relationship
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DOI：
10.1124/mol.51.4.535
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发表时间：
1997-04-01
影响因子：
3.6
通讯作者：
Holsboer, F
中科院分区：
文献类型：
--
作者：
Behl, C;Skutella, T;Holsboer, F
氧化应激诱导的神经元细胞死亡与不同的神经系统疾病和神经退行性疾病有关，其中一种疾病是阿尔茨海默病。使用阿尔茨海默病相关的β淀粉样蛋白，谷氨酸，过氧化氢，和丁硫氨酸亚砜亚胺，我们研究了雌激素对氧化应激诱导的细胞死亡的神经保护潜力。我们发现，17-β-雌二醇，其非雌激素的立体异构体，17-α-雌二醇，和相同的雌二醇衍生物可以防止细胞内过氧化物的积累，并最终，原代神经元，克隆海马细胞，和细胞的器官型海马切片的退化。雌激素的神经保护性抗氧化活性依赖于类固醇分子A环上C3位羟基的存在，但不依赖于雌激素受体的活化。
Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases; one such ailment is Alzheimer's disease. Using the Alzheimer's disease-associated amyloid beta protein, glutamate, hydrogen peroxide, and buthionine sulfoximine, we investigated the neuroprotective potential of estrogen against oxidative stress-induced cell death. We show that 17-beta-estradiol, its nonestrogenic stereoisomer, 17-alpha-estradiol, and same estradiet derivatives can prevent intracellular peroxide accumulation and, ultimately, the degeneration of primary neurons, clonal hippocampal cells, and cells in organotypic hippocampal slices. The neuroprotective antioxidant activity of estrogens is dependent on the presence of the hydroxyl group in the C3 position on the A ring of the steroid molecule but is independent of an activation of estrogen receptors.