Zemlyak Ilona, Brooke Sheila M, Sapolsky Robert M
Department of Biological Sciences, Gilbert Laboratory MC 5020, Stanford University, Stanford, CA 94305-5020, USA.
Brain Res. 2002 Dec 27;958(2):272-6. doi: 10.1016/s0006-8993(02)03558-8.
gp120, the coat protein of HIV, can be neurotoxic and is thought to contribute to AIDS-related dementia complex. Such toxicity involves activation of glutamate receptors, mobilization of free cytosolic calcium, and generation of oxygen radicals. We have previously shown that the estrogen 17beta-estradiol, in concentrations of 100 nM or higher, lessens the neurotoxicity of gp120 in hippocampal and cortical cultures, blunts gp120-induced calcium mobilization, and lessens the oxidative consequences. In this study, we examined the protective potential of other estrogens. We found gp120 neurotoxicity in hippocampal cultures to be significantly lessened by estrone, equilin and estriol, although with an order of magnitude less potent than 17beta-estradiol. We also found all four estrogens to blunt gp120-induced calcium mobilization, with estriol being more efficacious than the other three estrogens. These findings give insight both into the mechanisms of estrogenic protection (e.g. receptor-dependent versus independent actions) as well as into the potential therapeutic use of estrogens against AIDS-related dementia complex.
HIV的包膜蛋白gp120具有神经毒性，被认为与艾滋病相关痴呆综合征有关。这种毒性涉及谷氨酸受体的激活、游离胞质钙的动员以及氧自由基的产生。我们之前已经表明，浓度为100 nM或更高的雌激素17β-雌二醇可减轻海马和皮质培养物中gp120的神经毒性，抑制gp120诱导的钙动员，并减轻氧化后果。在本研究中，我们检测了其他雌激素的保护潜力。我们发现，雌酮、马萘雌酮和雌三醇可显著减轻海马培养物中gp120的神经毒性，尽管其效力比17β-雌二醇低一个数量级。我们还发现，所有四种雌激素均可抑制gp120诱导的钙动员，其中雌三醇比其他三种雌激素更有效。这些发现有助于深入了解雌激素保护的机制（例如受体依赖性与非依赖性作用）以及雌激素在治疗艾滋病相关痴呆综合征方面的潜在用途。
