Suppression of transcription factor Egr-1 by curcumin.
The transcription factor early growth response-1 gene product (Egr-1) is a member of the family of immediate early response genes and regulates a number of pathophysiologically relevant genes in vasculature that are involved in growth, differentiation, immune response, wound healing, and blood clotting. In the present study, we investigated the effect of curcumin, a natural plant phenolic compound known to exhibit anticarcinogenic, antioxidant, and antiinflammatory properties, on Egr-1 expression in endothelial cells and fibroblasts. Gel mobility shift assays showed that pretreatment of endothelial cells and fibroblasts with curcumin suppressed phorbol 12-myristate 13-acetate and serum-induced Egr-1 binding activity to the consensus Egr-1 binding site and also to the Egr-1 binding site present in the promoter of tissue factor gene. Western blot analysis revealed that curcumin inhibited phorbol 12-myristate 13-acetate-induced de novo synthesis of Egr-1 protein in endothelial cells. Suppression of Egr-1 protein expression in curcumin-treated cells stemmed from the suppression of Egr-1 mRNA. Northern blot analysis showed that curcumin inhibited serum and phorbol 12-myristate 13-acetate induced expression of tissue factor and urokinase-type plasminogen activator receptor mRNA in fibroblasts. Cumulatively, the data show that curcumin suppresses the induction of transcription factor Egr-1 and thereby modulates the expression of Egr-1-regulated genes in endothelial cells and fibroblasts.
Pendurthi
U R
UR
Department of Molecular Biology, The University of Texas Health Center at Tyler, 75708, USA. usha@uthct.edu
Rao
L V
LV
D001665:Binding Sites; D001769:Blood; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions; D051766:Early Growth Response Protein 1; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017874:Immediate-Early Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014157:Transcription Factors; D013925:Thromboplastin; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate