Bynum James A, Wang Xinyu, Stavchansky Salomon A, Bowman Phillip D
U.S. Army Institute of Surgical Research, San Antonio, TX, USA.
Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
Gene Regul Syst Bio. 2017 Apr 7;11:1177625017701106. doi: 10.1177/1177625017701106. eCollection 2017.
1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), a synthetic derivative of oleanolic acid that exhibits antioxidant and anti-inflammatory activity in several animal and in vitro models, has been shown to be beneficial if given after injury. Although induction of heme oxygenase 1 appears to be a major effector of cytoprotection, the mechanism by which the overall effect is mediated is largely unknown. This study evaluated temporal gene expression profiles to better characterize the early transcriptional events and their relationship to the dynamics of the cytoprotective response in human umbilical vein endothelial cells (HUVEC) to CDDO-Im. Time-course gene expression profiling was performed on HUVEC treated with CDDO-Im for 0.5, 1, 3, 6, and 24 hours. More than 10 000 genes were statistically altered in their expression in at least 1 time point across the time course. Large alterations in immediate-early gene expression were readily detectable within 0.5 hour after administration of CDDO-Im.
1-[2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酰基]咪唑（CDDO-Im）是齐墩果酸的一种合成衍生物，在多种动物模型和体外模型中均表现出抗氧化和抗炎活性，研究表明在损伤后给予该物质有益。虽然血红素加氧酶1的诱导似乎是细胞保护的主要效应器，但介导整体效应的机制在很大程度上尚不清楚。本研究评估了时间基因表达谱，以更好地表征人脐静脉内皮细胞（HUVEC）对CDDO-Im的早期转录事件及其与细胞保护反应动力学的关系。对用CDDO-Im处理0.5、1、3、6和24小时的HUVEC进行时间进程基因表达谱分析。在整个时间进程中，至少有1个时间点上超过10000个基因的表达发生了统计学改变。在给予CDDO-Im后0.5小时内即可轻易检测到早期即刻基因表达的大幅变化。
