Unspliced X-box-binding蛋白1 (XBP1)保护内皮细胞免受氧化应激与组蛋白脱乙酰酶3通过交互。
文章的细节
-
引用
复制到剪贴板 -
李马丁D, Y,杨J,王G, Margariti,江Z, Yu H, Zampetaki,胡锦涛Y,徐问,曾庆红L
Unspliced X-box-binding蛋白1 (XBP1)保护内皮细胞免受氧化应激与组蛋白脱乙酰酶3通过交互。
生物化学杂志。2014年10月31日;289 (44):30625 - 34。doi: 10.1074 / jbc.M114.571984。Epub 2014年9月4。
- PubMed ID
-
25190803 (在PubMed]
- 文摘
-
众所周知,动脉粥样硬化发生的地理位置在分支点扰动流易诱发斑块的发展通过引发氧化应激和炎症反应。在这项研究中,我们发现扰动流激活氧化反应通过调控的血红素加氧酶1 (HO-1) X-box-binding蛋白1 (XBP1)和组蛋白脱乙酰酶3 (HDAC3)端依赖的方式。扰动流与此同时上调unspliced XBP1 (XBP1u)和HDAC3 VEGF受体和PI3K / Akt-dependent方式。XBP1的存在是必要的老年病HDAC3蛋白质。超表达XBP1u和/或HDAC3 Akt1磷酸化,激活Nrf2蛋白质稳定和核易位和HO-1表达式。击倒XBP1u减少基础水平和扰动流Akt1磷酸化,Nrf2稳定,HO-1表达式。击倒的HDAC3切除XBP1u-mediated效果。哺乳动物雷帕霉素靶复杂2 (mTORC2)抑制剂,AZD2014,切除XBP1u HDAC3或干扰流量介导Akt1磷酸化,Nrf2核易位,HO-1表达式。放线菌素D和环己酰亚胺影响干扰流老年病的Nrf2蛋白质。击倒的Nrf2废除XBP1u HDAC3或干扰流HO-1老年病。 Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3, and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression.