G-protein-coupled receptor 30-mediated antiapoptotic effect of estrogen on spinal motor neurons following injury and its underlying mechanisms.
G-protein-coupled receptor 30-mediated antiapoptotic effect of estrogen on spinal motor neurons following injury and its underlying mechanisms.
复制标题
DOI：
10.3892/mmr.2015.3601
复制
发表时间：
2015-08
影响因子：
3.4
通讯作者：
Feng H
中科院分区：
文献类型：
--
作者：
Chen J;Hu R;Ge H;Duanmu W;Li Y;Xue X;Hu S;Feng H
脊髓损伤可导致严重的运动神经元功能障碍。g蛋白偶联受体30 （GPR30）在脊髓前角运动神经元中的表达通过雌激素信号介导神经保护。本研究探讨了GPR30介导的雌激素在脊髓损伤后的抗凋亡作用及其机制。体外培养大鼠脊髓运动神经元，建立氧葡萄糖剥夺（OGD）细胞模型。采用MTT法观察雌激素、雌激素激动剂G1和雌激素抑制剂G15对运动神经元的影响。流式细胞术检测E2、G1和G15对OGD后脊髓运动神经元凋亡的影响。用流式细胞术检测磷脂酰肌醇3-激酶/蛋白激酶B （PI3K/Akt）抑制剂LY294002的作用。建立大鼠脊髓损伤模型。体内给药E2、G1和E2+LY294002。分别于伤后3、7、14、21、28 d采用BBB （Basso-Beattie-Bresnahan）评分标准进行运动功能评分。雌激素组和G1组细胞活性高于溶剂组，E2+G15组细胞活性低于E2组（P<0.05）。OGD后，凋亡细胞比例显著升高（P<0.05）。雌激素组细胞凋亡比例显著低于溶剂组，E2+G15、E2+LY294002组细胞凋亡比例显著高于E2组（P<0.05）。E2和G1处理导致正常细胞和ogd后细胞中P-Akt表达上调。E2和G1组大鼠BBB评分均高于安慰剂组（P<0.05）。E2+LY294002组BBB评分低于E2组（P<0.05）。因此，雌激素似乎通过GPR30对OGD后的脊髓运动神经元发挥保护作用。PI3K/Akt通路可能是参与GPR30介导的雌激素相关抗凋亡作用的通路之一。
Spinal cord injury (SCI) may result in severe dysfunction of motor neurons. G-protein-coupled receptor 30 (GPR30) expression in the motor neurons of the ventral horn of the spinal cord mediates neuroprotection through estrogen signaling. The present study explored the antiapoptotic effect of estrogen, mediated by GPR30 following SCI, and the mechanisms underlying this effect. Spinal motor neurons from rats were cultured in vitro in order to establish cell models of oxygen and glucose deprivation (OGD). The effects of estrogen, the estrogen agonist, G1, and the estrogen inhibitor, G15, on motor neurons were observed using MTT assays. The effects of E2, G1 and G15 on spinal motor neuron apoptosis following OGD, were detected using flow cytometry. The role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) inhibitor, LY294002, was also determined using flow cytometry. Rat SCI models were established. E2, G1 and E2+LY294002 were administered in vivo. Motor function was scored at 3, 7, 14, 21 and 28 d following injury, using Basso-Beattie-Bresnahan (BBB) standards. Cell activity in the estrogen and G1 groups was higher than that in the solvent group, whereas cell activity in the E2+G15 group was lower than that in the E2 group (P<0.05). Following OGD, the proportion of apoptotic cells significantly increased (P<0.05). The proportion in the estrogen group was significantly lower than that in the solvent group, whereas the proportion of apoptotic cells in the E2+G15 and E2+LY294002 groups was higher than that in the E2 group (P<0.05). Treatment with E2 and G1 led to upregulation of P-Akt expression in normal cells and post-OGD cells. The BBB scores of rats in the E2 and G1 groups were higher than those in the placebo group (P<0.05). The BBB scores of the E2+LY294002 group were lower than those of the E2 group (P<0.05). Estrogen thus appears to exert a protective effect on spinal motor neurons following OGD, via GPR30. The PI3K/Akt pathway may be one of those involved in the estrogen-related antiapoptotic effects mediated by GPR30.
登录
查看更多内容
影响因子：
82.9
作者：
Crowe, MJ;Bresnahan, JC;Beattie, MS
通讯作者：
Beattie, MS
DOI：
10.1007/bf02576273
发表时间：
1992-06-01
期刊：
RESEARCH IN EXPERIMENTAL MEDICINE
影响因子：
--
作者：
AKDEMIR, H;PASAOGLU, A;KURTSOY, A
通讯作者：
KURTSOY, A
影响因子：
3.1
作者：
Du, Dong-Shu;Ma, Xiao-Bo;Qiao, Wei-Li
通讯作者：
Qiao, Wei-Li
影响因子：
9
作者：
Macias, Carlos Aitor;Rosengart, Matthew R.;Angus, Derek C.
通讯作者：
Angus, Derek C.
胶质疤痕和神经再生：慢性脊髓损伤的组织学、功能和磁共振成像分析实验室研究
影响因子：
2.8
作者：
Hu, Rong;Zhou, Jianjun;Feng, Hua
通讯作者：
Feng, Hua