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Title: Corticosteroids induce cyclooxygenase 1 expression in cardiomyocytes: role of glucocorticoid receptor and Sp3 transcription factor.

Authors: Sun, Haipeng; Sheveleva, Elena; Chen, Qin M

Published In Mol Endocrinol, (2008 Sep)

Abstract: Cyclooxygenase (COX) encodes a rate-limiting enzyme in the biosynthesis of prostanoids. Although COX-1 is constitutively expressed in many tissues, we found that glucocorticoids cause elevated expression of COX-1 gene in cardiomyocytes. Corticosterone (CT) at physiologically relevant doses (0.05-1 microm) induces transcriptional activation of COX-1 gene as shown by nuclear run-on and promoter reporter assays. An antagonist of glucocorticoid receptor (GR), mifepristone, prevented CT from inducing COX-1. COX-1 gene promoter deletion and mutation studies indicate a role of Sp transcription factors in CT-induced COX-1 gene. EMSAs or chromatin immunoprecipitation assays suggest that GR and Sp3 transcription factor bind to the promoter of COX-1 gene. Coimmunoprecipitation assays found an association of GR with Sp3. Silencing Sp3 protein with small interfering RNA suppressed CT-induced COX-1 promoter activation. Our data suggest that activated GR interacts with Sp3 transcription factor in binding to COX-1 promoter to enhance COX-1 gene expression in cardiomyocytes.

PubMed ID: 18599619 Exiting the NIEHS site

MeSH Terms: Animals; Base Composition; Base Sequence; Cells, Cultured; Corticosterone/pharmacology*; Cyclooxygenase 1/genetics*; DNA/genetics; DNA/metabolism; Membrane Proteins/genetics*; Mifepristone/pharmacology; Myocytes, Cardiac/drug effects*; Myocytes, Cardiac/metabolism*; Promoter Regions, Genetic/drug effects; RNA, Small Interfering/genetics; Rats; Receptors, Glucocorticoid/antagonists & inhibitors; Receptors, Glucocorticoid/metabolism*; Sp3 Transcription Factor/metabolism*; Transcriptional Activation/drug effects

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