17β-Estradiol-mediated increase in Cu/Zn superoxide dismutase expression in the brain: a mechanism to protect neurons from ischemia.
17β-Estradiol-mediated increase in Cu/Zn superoxide dismutase expression in the brain: a mechanism to protect neurons from ischemia.
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DOI：
10.1016/j.jsbmb.2011.06.008
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发表时间：
2011-11
影响因子：
4.1
通讯作者：
Nardulli, Ann M.
中科院分区：
文献类型：
--
作者：
Rao, Abhi K.;Dietrich, Alicia K.;Ziegler, Yvonne S.;Nardulli, Ann M.
大量研究表明，17β-雌二醇（E2）可保护脑缺血，但这种激素产生保护作用的机制尚不清楚。有趣的是，像E2一样，氧化应激反应蛋白Cu/Zn超氧化物歧化酶（SOD 1）的过表达也可以保护大脑免受缺血的影响，SOD 1在调节活性氧中起着关键作用。因为我们以前表明，E2处理培养的乳腺细胞增加SOD 1的表达，我们假设，E2可能会增加SOD 1在大脑中的表达，这种E2介导的SOD 1表达的增加可能有助于保护大脑免受缺血。我们现在表明，SOD 1在皮质神经元中表达，SOD 1的表达增加暴露的脑切片培养E2，和E2介导的增加SOD 1的表达进一步增强暴露的脑切片培养增加超氧化物水平或氧和葡萄糖剥夺。重要的是，当皮质神经元暴露于增加的超氧化物水平和蛋白质和DNA损伤的标志物时，分别测量硝基酪氨酸和8-氧代鸟嘌呤，蛋白质和DNA损伤都减少。事实上，E2降低了脑切片培养物中的硝基酪氨酸和8-氧代鸟嘌呤水平，无论它们是否暴露于增加的超氧化物水平。同样，当脑切片培养物用E2处理并剥夺氧气和葡萄糖时，8-氧代鸟嘌呤水平降低。总之，这些研究提供了E2治疗，SOD 1表达和神经保护之间的关键联系，并有助于定义E2介导的神经保护可能被赋予的机制。
A number of studies have demonstrated that 17β-estradiol (E2) protects the brain from ischemia and yet, the mechanism by which this hormone brings about its protective effect is unclear. Interestingly, like E2, overexpression of the oxidative stress response protein Cu/Zn superoxide dismutase (SOD1), which plays a critical role in regulating reactive oxygen species, also protects the brain from ischemia. Because we previously showed that E2 treatment of cultured mammary cells increases SOD1 expression, we hypothesized that E2 might increase SOD1 expression in the brain and that this E2-mediated increase in SOD1 expression might help to protect the brain from ischemia. We now show that SOD1 is expressed in cortical neurons, that SOD1 expression is increased by exposure of brain slice cultures to E2, and that the E2–mediated increase in SOD1 expression is further augmented by exposure of brain slice cultures to increased superoxide levels or oxygen and glucose deprivation. Importantly, when cortical neurons are exposed to increased superoxide levels and markers of protein and DNA damage, nitrotyrosine and 8-oxoguanine, respectively, are measured, both protein and DNA damage is reduced. In fact, E2 reduces nitrotyrosine and 8-oxoguanine levels in brain slice cultures regardless of whether they have or have not been exposed to increased superoxide levels. Likewise, when brain slice cultures are treated with E2 and deprived of oxygen and glucose, 8-oxoguanine levels are reduced. Taken together, these studies provide a critical link between E2 treatment, SOD1 expression, and neuroprotection and help to define a mechanism through which E2– mediated neuroprotection may be conferred.
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影响因子：
5.3
作者：
Deng, Ying;Thompson, Brian M.;Hall, Edward D.
通讯作者：
Hall, Edward D.
DOI：
10.1073/pnas.88.24.11158
发表时间：
1991-12-01
影响因子：
11.1
作者：
KINOUCHI, H;EPSTEIN, CJ;CHAN, PH
通讯作者：
CHAN, PH
影响因子：
--
作者：
Hewitt, SC;Deroo, BJ;Korach, KS
通讯作者：
Korach, KS
DOI：
10.1097/00004647-199905000-00003
发表时间：
1999-05-01
影响因子：
6.3
作者：
Fujimura, M;Morita-Fujimura, Y;Chan, PH
通讯作者：
Chan, PH
影响因子：
3.4
作者：
Moser, KV;Schmidt-Kastner, R;Humpel, C
通讯作者：
Humpel, C