Androgens selectively protect against apoptosis in hippocampal neurones.
Androgens selectively protect against apoptosis in hippocampal neurones.
复制标题
DOI：
10.1111/j.1365-2826.2010.02044.x
复制
发表时间：
2010-09
影响因子：
3.2
通讯作者：
Pike CJ
中科院分区：
文献类型：
--
作者：
Nguyen TV;Jayaraman A;Quaglino A;Pike CJ
雄激素可以保护神经元免受损伤，但雄激素的神经保护作用在特异性或机制方面都不是很好。在这里，我们比较了雄激素保护神经元免受一系列侮辱的能力，根据经验，这些侮辱通过凋亡或非凋亡机制诱导细胞死亡。定义但不包括细胞凋亡的三个标准是：caspase抑制的保护，蛋白质合成抑制的保护，以及固缩核的存在。根据这些标准，β-淀粉样蛋白、星形孢子素和凋亡激活剂II诱导的细胞死亡包括凋亡，而过氧化氢(H_2O_2)、铁、钙离子载体和3-硝基丙酸诱导的细胞死亡具有非凋亡特征。用睾酮或双氢睾酮预处理海马神经元可减轻β-淀粉样蛋白、星形孢子素和凋亡激活剂II诱导的细胞死亡，但不影响其他因素。抗氧化剂Trolox不能减少β-淀粉样蛋白、星形孢子素和凋亡激活剂II诱导的细胞死亡，但对H_2O_2和铁有保护作用。同样，超生理浓度的雌激素减少了过氧化氢和铁诱导的细胞死亡，这是雄激素没有观察到的效果。我们还表明，雌激素通路的激活不是雄激素神经保护所必需的。这些数据表明，雄激素直接激活了一种神经保护机制，该机制专用于抑制细胞死亡，涉及细胞凋亡。确定雄激素神经保护的特异性可能使雄激素化合物的开发用于治疗神经退行性疾病。
Androgens can protect neurones from injury, but androgen neuroprotection is not well characterised in terms of either specificity or mechanism. Here, we compared the ability of androgens to protect neurones against a panel of insults, empirically determined to induce cell death by apoptotic or non-apoptotic mechanisms. Three criteria defining, but not inclusive of apoptosis are: protection by caspase inhibition, protection by protein synthesis inhibition, and presence of pyknotic nuclei. According to these criteria, β-amyloid, staurosporine, and Apoptosis Activator II induced cell death involving apoptosis, while hydrogen peroxide (H2O2), iron, calcium ionophore, and 3-nitropropionic acid induced cell death featuring non-apoptotic characteristics. Pretreatment of hippocampal neurones with testosterone or dihydrotestosterone attenuated cell death induced by β-amyloid, staurosporine, and Apoptosis Activator II, but none of the other insults. The anti-oxidant Trolox did not reduce cell death induced by β-amyloid, staurosporine, and Apoptosis Activator II, but did protect against H2O2 and iron. Similarly, a supra-physiological concentration of oestrogen reduced cell death induced by H2O2 and iron, an effect not observed with androgens. We also show that activation of oestrogen pathways was not necessary for androgen neuroprotection. These data suggest that androgens directly activate a neuroprotective mechanism specific to inhibition of cell death involving apoptosis. Determining the specificity of androgen neuroprotection may enable the development of androgen compounds for the treatment of neurodegenerative disorders.
登录
查看更多内容
影响因子：
4.7
作者：
Hammond, J;Le, Q;LeBlanc, A
通讯作者：
LeBlanc, A
影响因子：
3.3
作者：
Holmes, M. M.;McCutcheon, J.;Forger, N. G.
通讯作者：
Forger, N. G.
影响因子：
2.9
作者：
Hawk, T;Zhang, YQ;Simpkins, JW
通讯作者：
Simpkins, JW
DOI：
10.1073/pnas.97.3.1202
发表时间：
2000-02-01
影响因子：
11.1
作者：
Gouras, GK;Xu, HX;Greengard, P
通讯作者：
Greengard, P
DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL