Wang Yajing, Wang Zhaoxia, Wang Lianyun, Zhou Ying, Zhao Yangxing, Liu Liming, Yao Chenjiang, Qiao Zhongdong
School of Medicine, Shanghai Jiao Tong University, 800 Dongchuan Rd., 200240 Shanghai, PR China.
Int Immunopharmacol. 2006 Jun;6(6):892-902. doi: 10.1016/j.intimp.2005.12.006. Epub 2006 Jan 23.
Although gonadal hormone mostly causes genotropic actions through the members of nuclear receptor family, it also can regulate these actions via membrane receptor. To explore the possibility of plasma membrane estrogen receptors (mER) mediating genotropic events, we have investigated estrogen's effect on nicotine-stimulated adhesion molecule expression and evaluated whether this effect depends on calcium, MAPK signal pathway. Fluorescence Spectroscopy analysis of Ca2+ from human umbilical vein endothelial cells (HUVECs) showed through mER, estrogen induced a rapid rise of intracellular free Ca2+ concentration and this rise could not be inhibited by tamoxifen (classic ER inhibitor). In the context of nicotine stimulating, however, estrogen attenuated phosphorylation of mitogen-activated protein kinase (MAPK) family members, extracellular signal regulated kinase 1/2 (ERK1/2), p38 but not c-Jun-N-terminal kinase (JNK) in HUVECs and this effect could not still be prevented by tamoxifen. In the meantime, estrogen also down-regulated surface/soluble vascular cell adhesion molecule (VCAM-1, sVCAM-1) and endothelial selectin (E-selectin, sE-selectin) levels, which was not abolished by tamoxifen either. Moreover, calcium chelator BAPTA, ERK1/2 inhibitor PD98059, p38 inhibitor SB203580 significantly reduced the production of nicotine-activated surface/soluble VCAM-1 and E-selectin and both of the remained levels were no longer regulated by estrogen. Our study here provides the information of decrease effect of mER-mediated estrogen through Ca2+ and ERK1/2, p38 MAPK signaling pathway on nicotine-stimulated expression of surface/soluble VCAM-1 and E-selectin in HUVECs.
尽管性腺激素大多通过核受体家族成员引起基因otropic作用，但它也可以通过膜受体调节这些作用。为了探索质膜雌激素受体（mER）介导基因otropic事件的可能性，我们研究了雌激素对尼古丁刺激的黏附分子表达的影响，并评估了这种影响是否依赖于钙、丝裂原活化蛋白激酶（MAPK）信号通路。对人脐静脉内皮细胞（HUVECs）进行的Ca2+荧光光谱分析表明，通过mER，雌激素诱导细胞内游离Ca2+浓度迅速升高，而这种升高不能被他莫昔芬（经典的ER抑制剂）抑制。然而，在尼古丁刺激的情况下，雌激素减弱了HUVECs中丝裂原活化蛋白激酶（MAPK）家族成员细胞外信号调节激酶1/2（ERK1/2）、p38的磷酸化，但不影响c-Jun氨基末端激酶（JNK），并且这种作用仍然不能被他莫昔芬阻止。同时，雌激素还下调了表面/可溶性血管细胞黏附分子（VCAM-1、sVCAM-1）和内皮选择素（E-选择素、sE-选择素）的水平，这也不能被他莫昔芬消除。此外，钙螯合剂BAPTA、ERK1/2抑制剂PD98059、p38抑制剂SB203580显著降低了尼古丁激活的表面/可溶性VCAM-1和E-选择素的产生，并且这两种剩余水平不再受雌激素调节。我们这里这项研究提供了信息，即mER介导的雌激素通过Ca2+以及ERK1/2、p38 MAPK信号通路对尼古丁刺激的HUVECs表面/可溶性VCAM-1和E-选择素表达具有降低作用。
