雌激素快速影响大鼠发育期海马NMDA受体活性的机制  

Mechanisms Underlying The Rapid Effects of Estrogen on NMDA Receptor Activity in Developmental Rat Hippocampus

作　　者：罗清清[1] 徐晓虹[1,2] 李涛[1] 叶银萍[1,2] 田栋[1] 陈蕾[1,2] 

机构地区：[1]浙江师范大学化学与生命科学学院,浙江金华321004 [2]浙江师范大学生态研究所,浙江金华321004

出　　处：《生物物理学报》2010年第10期919-928,共10页Acta Biophysica Sinica

基　　金：国家自然科学基金项目(30872087;30771783);浙江省自然科学基金重点项目(Z2090955)

摘　　要：为了探讨雌激素对发育期大鼠海马NMDA受体活性的快速影响,对出生后18d的雄性大鼠进行苯甲酸雌二醇皮下注射,1h后用WesternBlot检测海马NMDA受体NR1和NR2B亚基、雌激素β受体、ERK1/2蛋白的表达,以及NR2B和ERK1/2的磷酸化水平;并通过海马内给予雌激素受体拮抗剂ICI182,780和MEK1/2抑制剂U0126预处理,进一步分析苯甲酸雌二醇影响NR2B和ERK1/2磷酸化的作用机制。结果显示,苯甲酸雌二醇不影响NR1、NR2B、ERβ和ERK1/2的表达,但能快速增强NR2B和ERK1/2的磷酸化水平。雌激素受体拮抗剂ICI182,780和MEK1/2抑制剂U0126均能明显抑制苯甲酸雌二醇诱导的NR2B和ERK1/2磷酸化水平的增加。以上结果提示,雌激素可能通过雌激素受体的非基因组机制激活ERK/MAPK信号转导通路,快速诱导NMDA受体NR2B亚基磷酸化,激活NMDA受体。In the present study, we investigated the signaling mechanisms underlying the rapid effects of estrogen on the regulation of NMDA receptor activity in the developmental hippocampus of rats.Pups at the age of postnatal day 18 were injected subcutaneously with estradiol benzoate （EB）.After 1 h, western blot was used to determine the expressions of NMDA receptor subunits NR1, NR2B, estrogen receptor beta （ERβ） and ERK1/2.An estrogen receptor antagonist, ICI 182,780, or a MEK1/2 inhibitor, U0126, was used to examine the potential involvement of estrogen receptor and ERK/MAPK signaling transduction pathway in the effects of EB on the activity of NR2B.EB treatment did not affect the expressions of NR1, NR2B, ERβ and ERK1/2, but rapidly increased the levels of NR2B phosphorylation and ERK phosphorylation.Co-treatment of ICI 182,780 or U0126 with EB significantly attenuated EB-induced phosphorylations of NR2B and ERK.These data suggest that estrogen is able to rapidly activated ERK/MAPK signaling pathway to modulate the activation of NR2B in the developing hippocampus of rats via estrogen receptor.

关 键 词：雌激素 雌激素受体 NMDA受体磷酸化 ERK1/2 

分 类 号：Q735[生物学—分子生物学]