Huang Ying, Huang Ya-Lin, Zhang Sun, Zhu Yi-Chun, Yao Tai
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China.
Brain Res. 2004 Nov 12;1026(2):254-60. doi: 10.1016/j.brainres.2004.08.038.
Increasing lines of evidence indicate that estrogen acts as a neuroprotective agent through a nongenomic mechanism. We tested the hypothesis that 17beta-estradiol could rapidly attenuate glutamate-induced calcium (Ca2+) overload in rat primary hippocampal neurons via a membrane receptor-dependent mechanism. The bulk cytosolic intracellular Ca2+ level was measured in neurons with fluorescent Ca2+ probe fluo3. Preexposure of primary cultured hippocampal neurons to 17beta-estradiol for 3 min attenuated intracellular Ca2+ increase induced by glutamate in a concentration-dependent manner. The action of 17beta-estradiol was reversible after washout. Administration of membrane-impermeable 17beta-estradiol conjugated to bovine serum albumin (E2-BSA) produced the same effect, suggesting possible involvement of cell membrane receptors. ICI 182,780, a specific estrogen receptor (ER) antagonist, blocked the neuronal response to 17beta-estradiol and estradiol BSA, indicating a role of specific ERs. The present study demonstrates that 17beta-estradiol acutely reduces glutamate-stimulated intracellular Ca2+ increase via ERs probably on the cell surface of the hippocampal neurons.
越来越多的证据表明，雌激素通过非基因组机制发挥神经保护作用。我们验证了以下假说：17β-雌二醇可通过膜受体依赖性机制迅速减轻谷氨酸诱导的大鼠原代海马神经元钙（Ca2+）超载。使用荧光Ca2+探针fluo3测量神经元中胞质内Ca2+的总体水平。将原代培养的海马神经元预先暴露于17β-雌二醇3分钟，可浓度依赖性地减轻谷氨酸诱导的细胞内Ca2+增加。洗脱后，17β-雌二醇的作用是可逆的。给予与牛血清白蛋白偶联的膜不可渗透的17β-雌二醇（E2-BSA）产生相同的效果，提示可能涉及细胞膜受体。特异性雌激素受体（ER）拮抗剂ICI 182,780可阻断神经元对17β-雌二醇和雌二醇BSA的反应，表明特异性ER的作用。本研究表明，17β-雌二醇可能通过海马神经元细胞表面的ER急性减少谷氨酸刺激引起的细胞内Ca2+增加。
