转录因子GATA结合蛋白3在家族性阿尔茨海默病发病机制中的作用

The study on the role of transcription factor GATA binding protein 3 in familial Alzheimer＇ s disease pathogenesis

目的 探讨家族性阿尔茨海默病（Alzheimer＇s disease,AD）相关的早老素1（presenilin-1,PS-1）V97L突变引起胰岛素降解酶（insulin degrading enzyme,IDE）降低的机制.方法 应用转录因子活性芯片技术检测转录因子活性的差异,再用Western b1ot法验证芯片结果.结果 芯片结合MatInspector软件分析发现,上调了5.5倍的转录因子GATA结合蛋白3（GATA binding protein 3,GATA-3）在IDE启动子上有结合位点,并对IDE起负性调控作用.Westem b1ot也证实稳定转染PS-1 V97L细胞系中GATA-3蛋白表达明显增高.结论 PS-1 V97L突变可能通过上调转录因子GATA-3抑制IDE的表达,影响β-淀粉样蛋白42含量进而参与AD的发生.

Objective To investigate the mechanisms of decreasing insulin degrading enzyme （IDE） level by mutation V97L in the gene presenilin 1 （PS-1）.Methods Transcription factor GATA binding protein 3 （GATA-3） activity was assessed by protein/DNA array and verified by Western blot in SH-SY5Y cells transfected by PS-1 mutation V97L.Results Protein/DNA array and Western blot revealed that there was increased transcript factor activity （5.5 times high） and protein level of GATA-3 in V97L-PS-1 transfected SH-SY5Y cells.Transcription factor GATA-3 can bind to the IDE promoter and negatively control the IDE transcription level.Conclusion PS-1 mutation V97L may regulate the transcription of IDE via GATA-3, and subsequently involve in deposition of Aβ42 and development of Alzheimer＇s disease.