Lu Aigang, Ran Rui-qiong, Clark Joseph, Reilly Melinda, Nee Alex, Sharp Frank R
Department of Neurology and Neurosciences Program, Vontz Center for Molecular Studies, University of Cincinnati, Cincinnati, Ohio 45267, USA.
J Cereb Blood Flow Metab. 2002 Feb;22(2):183-95. doi: 10.1097/00004647-200202000-00006.
Estradiol reduces brain injury from many diseases, including stroke and trauma. To investigate the molecular mechanisms of this protection, the effects of 17-beta-estradiol on heat shock protein (HSP) expression were studied in normal male and female rats and in male gerbils after global ischemia. 17-beta-estradiol was given intraperitoneally (46 or 460 ng/kg, or 4.6 microg/kg) and Western blots performed for HSPs. 17-beta-estradiol increased hemeoxygenase-1, HSP25/27, and HSP70 in the brain of male and female rats. Six hours after the administration of 17-beta-estradiol, hemeoxygenase-1 increased 3.9-fold (460 ng/kg) and 5.4-fold (4.6 microg/kg), HSP25/27 increased 2.1-fold (4.6 microg/kg), and Hsp70 increased 2.3-fold (460 ng/kg). Immunocytochemistry showed that hemeoxygenase-1, HSP25/27,and HSP70 induction was localized to cerebral arteries in male rats, possibly in vascular smooth muscle cells. 17-beta-estradiol was injected intraperitoneally 20 minutes before transient occlusion of both carotids in adult gerbils. Six hours after global cerebral ischemia, 17-beta-estradiol (460 ng/kg) increased levels of hemeoxygenase-1 protein 2.4-fold compared with ischemia alone, and HSP25/27 levels increased 1.8-fold compared with ischemia alone. Hemeoxygenase-1 was induced in striatal oligodendrocytes and hippocampal neurons, and HSP25/27 levels increased in striatal astrocytes and hippocampal neurons. Finally, Western blot analysis confirmed that estrogen induced heat shock factor-1, providing a possible mechanism by which estrogen induces HSPs in brain and other tissues. The induction of HSPs may be an important mechanism for estrogen protection against cerebral ischemia and other types of injury.
雌二醇可减轻包括中风和创伤在内的多种疾病所导致的脑损伤。为研究这种保护作用的分子机制，我们在正常雄性和雌性大鼠以及全脑缺血后的雄性沙鼠中，研究了17-β-雌二醇对热休克蛋白（HSP）表达的影响。腹腔注射17-β-雌二醇（46或460 ng/kg，或4.6 μg/kg），并对热休克蛋白进行蛋白质印迹分析。17-β-雌二醇可增加雄性和雌性大鼠脑中的血红素加氧酶-1、HSP25/27和HSP70。在给予17-β-雌二醇6小时后，血红素加氧酶-1增加了3.9倍（460 ng/kg）和5.4倍（4.6 μg/kg），HSP25/27增加了2.1倍（4.6 μg/kg），Hsp70增加了2.3倍（460 ng/kg）。免疫细胞化学显示，血红素加氧酶-1、HSP25/27和HSP70的诱导定位于雄性大鼠的脑动脉，可能位于血管平滑肌细胞中。在成年沙鼠双侧颈动脉短暂闭塞前20分钟，腹腔注射17-β-雌二醇。全脑缺血6小时后，与单纯缺血相比，17-β-雌二醇（460 ng/kg）使血红素加氧酶-1蛋白水平增加了2.4倍，HSP25/27水平增加了1.8倍。血红素加氧酶-1在纹状体少突胶质细胞和海马神经元中被诱导，HSP25/27水平在纹状体星形胶质细胞和海马神经元中增加。最后，蛋白质印迹分析证实雌激素诱导热休克因子-1，这为雌激素在脑和其他组织中诱导热休克蛋白提供了一种可能的机制。热休克蛋白的诱导可能是雌激素保护脑免受缺血和其他类型损伤的重要机制。
