Time Course Expression Analysis of 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole Induction of Cytoprotection in Human Endothelial Cells

Abstract

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.

Deep insights into the response of human cervical carcinoma cells to a new cyano enone-bearing triterpenoid soloxolone methyl: a transcriptome analysis

“…Observed SM-induced up-regulation of KLF4 is in accordance with published data: it was shown that CDODA-Me and cyano enone-bearing derivative of betulinic acid induced KLF4 expression in colon cancer cells (1-5 μM (SW480, HT-29, HCT-15 cells (12 h)) and 5-10 μM (SW80, HT-29 cells (24 h)), respectively) [53, 126]. Along with KLF4 , other CESC-associated DEGs DUSP1 , EGR1 and FOS were found to be sensitive to treatment with cyano enone-bearing triterpenoids: up-regulation of these genes and their proteins were detected in HUVEC and VC1 cells treated by CDDO-Im (0.05-0.2 μM (0.5–6 h)) [66, 127, 128].…”

Cytoprotective Effects of Natural Compounds against Oxidative Stress

“…The possible mechanisms for CDDO-Im cytoprotection were attributed to the induction of HO-1, activation of Nrf2 signaling pathway in response to oxidative stress, and elevation of the expression of heat shock proteins [ 8 ]. A recent time-course study revealed gene expression pattern induced by CDDO-Im in human endothelial cells [ 13 ]. Genes that upregulated by this compound within an hour include early growth response gene 1, 2, and 3.…”

“…This activation of RAF1 leads to phosphorylation of the tyrosine and threonine residues of MAP2K1which then leads to activation and transduction of the MAPK/ERK pathway. Another crucial element of CDDO-Im analysis by Bynum et al [ 13 ] is the identification of the DUSP1 gene at the 0.5 hour point. There are several anti-inflammatory drugs that also act through the DUSP1 gene including glucocorticoids [ 65 ].…”