Biochemistry and Molecular Biology Laboratory, Centre of Advanced Study, Department of Zoology, Banaras Hindu University, Varanasi, 221 005, India.
Neurochem Res. 2012 Feb;37(2):448-53. doi: 10.1007/s11064-011-0631-y. Epub 2011 Oct 20.
Following the binding of estrogen to estrogen receptor (ER)β ligand binding domain (LBD) and its interaction with the target genes, a host of nuclear proteins is recruited to regulate the expression of specific genes(s). It is not known which proteins interact with ERβLBD and whether they vary with age and sex in the brain. Therefore, using pull down assay, immunoprecipitation and immunoblotting, we report that cell signaling molecules Trk A and Src interacted with ERβLBD, and showed alteration in the level of interaction and expression in the brain of AKR strain young (6 weeks), adult (25 weeks) and old (70 weeks) mice of both sexes. Trk A showed decreasing interaction with age, and lower expression in adult as compared to young and old males, whereas female mice exhibited decline in both interaction and expression as a function of age. On the other hand, Src interaction with ERβLBD decreased, but its expression increased with age in males, whereas the interaction and expression was lower in adult but higher in old as compared to young females. These findings suggest the implication of Trk A and Src in ERβ mediated brain functions and related disorders during aging.
雌激素与雌激素受体（ER）β配体结合域（LBD）结合并与其靶基因相互作用后，会募集大量核蛋白来调节特定基因的表达。目前尚不清楚哪些蛋白与 ERβLBD 相互作用，以及它们在大脑中是否随年龄和性别而变化。因此，我们通过下拉实验、免疫沉淀和免疫印迹实验报告称，细胞信号分子 Trk A 和 Src 与 ERβLBD 相互作用，并且在 AKR 品系年轻（6 周）、成年（25 周）和老年（70 周）雌雄小鼠的大脑中，其相互作用和表达水平发生了改变。Trk A 的相互作用随年龄的增长而降低，成年雄性小鼠的表达水平较年轻和老年雄性小鼠低，而雌性小鼠的相互作用和表达水平则随年龄的增长而降低。另一方面，Src 与 ERβLBD 的相互作用减少，但在雄性小鼠中随年龄的增长而增加，而成年雌性小鼠的相互作用和表达水平低于年轻雌性小鼠，但老年雌性小鼠的相互作用和表达水平高于年轻雌性小鼠。这些发现表明，Trk A 和 Src 参与了 ERβ 介导的大脑功能和与衰老相关的疾病。
