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Network Analysis of the Cytoprotective Effect of CDDO‐IM against Oxidant Stress in Human Umbilical Vein Endothelial Cells (HUVEC)
Author(s) -
Wang Xinyu,
Bynum James,
Stavchansky Salomon,
Bowman Phillip
Publication year - 2010
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.24.1_supplement.760.1
Subject(s) - cytoprotection , caffeic acid phenethyl ester , umbilical vein , chemistry , oxidative stress , angiogenesis , heme oxygenase , microbiology and biotechnology , signal transduction , biochemistry , survivin , caffeic acid , antioxidant , apoptosis , enzyme , cancer research , biology , heme , in vitro
1[2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oyl]imidazole (CDDO‐IM), a derivative of oleanolic acid, has been demonstrated to possess anti‐inflammatory activity and to prevent tumor progression in mice if present when tumor cells were administered. CDDO‐IM (kindly supplied by Dr. Michael Sporn, Dartmouth University) was compared to the phenolic cytoprotectant caffeic acid phenethyl ester (CAPE), and CDDO‐IM at 200 nM was more effective than CAPE at 20 μM in protecting HUVEC from oxidant stress produced by menadione. Since CDDO‐IM possesses no antioxidant activity we tested it for transcriptional activation with whole genome microarray and found that about 700 genes were up or down‐regulated by CDDO‐IM. In addition to up‐regulating heme oxygenase‐1, a well‐known cytoprotective gene, it also induced members of the heat shock protein family. Submission of genes altered in their expression by greater than two fold up‐regulation to Ingenuity Pathway Analysis (IPA) produced networks related to cellular development, growth and proliferation, cell signaling, and canonical pathways including NRF2‐mediated oxidative stress response and PPAR signaling indicating that cytoprotection involves multiple pathways in addition to the well described phase II enzyme induction.