Nuclear estrogen receptor-independent neuroprotection by estratrienes: A novel interaction with glutathione
Nuclear estrogen receptor-independent neuroprotection by estratrienes: A novel interaction with glutathione
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DOI：
10.1016/s0306-4522(97)00595-2
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发表时间：
1998-05-01
期刊：
影响因子：
3.3
通讯作者：
Simpkins, JW
中科院分区：
文献类型：
--
作者：
Green, PS;Gridley, KE;Simpkins, JW
绝经后雌激素替代疗法与降低患阿尔茨海默病的风险有关，并且在几项小型临床试验中被报道可以改善认知功能。本研究使用暴露于神经毒性β-淀粉样肽的小鼠神经元细胞系HT-22，评估了雌激素神经保护作用对雌激素受体存在的依赖性。这些细胞缺乏功能性雌激素受体。淀粉样肽杀死了 50-60% 的这些细胞，同时用三种雌三烯、β-雌二醇、α-雌二醇或 estratrien-3-ol 中的任何一种进行治疗，产生剂量依赖性保护。这种雌激素神经保护的效力取决于培养基中谷胱甘肽的存在。培养基中还原型谷胱甘肽的存在使雌激素的神经保护效力平均增加400倍，这些结果表明核雌激素受体对于雌激素的神经保护作用不是必需的；然而，在生理学和药理学相关剂量下，雌三烯神经保护需要细胞外环境中存在适当的抗氧化剂。这些数据表明雌激素-抗氧化剂联合疗法治疗阿尔茨海默病等神经退行性疾病的可能性。 (C) 1998 国际广播组织。由爱思唯尔科学有限公司出版
Post-menopausal estrogen replacement therapy is associated with a reduction in the risk of Alzheimer's disease and has been reported to improve cognitive functioning in several small clinical trials, The present study evaluates the dependence of estrogenic neuroprotection on the presence of estrogen receptors using the murine neuronal cell line, HT-22, exposed to the neurotoxic beta-amyloid peptide. These cells lack functional estrogen receptors. The amyloid peptide killed 50-60% of these cells and concurrent treatment with either of three estratrienes, beta-estradiol, alpha-estradiol, or estratrien-3-ol, resulted in a dose-dependent protection, The potency of this estrogen neuroprotection was dependent on the presence of glutathione in the culture media, The presence of reduced glutathione in the media increases the neuroprotective potency of estrogens by an average of 400-fold, These results demonstrate that a nuclear estrogen receptor is not necessary for the neuroprotective actions of estrogens; however, the presence of an appropriate antioxidant in the extracellular milieu is needed for estratriene neuroprotection at physiologically and pharmacologically relevant doses. These data suggest the possibility of combined estrogen-antioxidant therapy for neurodegenerative diseases such as Alzheimer's disease. (C) 1998 IBRO. Published by Elsevier Science Ltd.