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Time Course and Network Analysis of 1‐[2‐Cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oyl]imidizole (CDDO‐IM) Induction of Cytoprotective Genes in Human Umbilical Vein Endothelial Cells (HUVEC) Against Oxidant Stress
Author(s) -
Wang Xinyu,
Bynum James,
Bowman Phillip D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1090.3
Subject(s) - hmox1 , microarray analysis techniques , gclm , gene , chemistry , heme oxygenase , junb , gene expression , aldehyde dehydrogenase , microbiology and biotechnology , biology , downregulation and upregulation , biochemistry , gclc , heme , enzyme
CDDO‐IM, a synthetic triterpenoid‐derived compound exhibits cytoprotective activity, possibly via transcriptional activation of the phase II response. To understand the genes responsible and signaling pathways involved in initiating and driving this effect we performed gene expression analysis with whole genome microarrays at 0.5, 1, 3, 6 and 24 h following treatment with a cytoprotective dose of 200 nM and compared it to 0.1% DMSO vehicle control. Microarray data were analyzed using BRB array tool that identified about 10,000 genes that were significantly altered following CDDO‐IM treatment. Submission of these genes altered in their expression by greater than two fold to Ingenuity Pathway Analysis (IPA) indicated several canonical pathways were importantly involved in cytoprotective function. Among them, nrf2‐mediated oxidative stress response genes known to activate the phase II response were some of the earliest to be upregulated. In addition, Genes for FOS and JUNB that form the AP‐1 transcription complex were expressed at high levels at 0.5 and 1 hr CDDO‐IM treatment as were the early growth response genes such as EGR1. Expression of these genes may drive the nrf2 pathway including the induction of heme oxygenase‐1, heat shock protein family DNAJ (Hsp40), glutamate‐cysteine ligase catalytic subunit, and NAD(P)H:quinone oxidoreductase after 3 and 6 hr CDDO‐IM treatment.