This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, H. Articles by Chen, Q. M. Search for Related Content PubMed PubMed Citation Articles by Sun, H. Articles by Chen, Q. M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB RU-486

Corticosteroids Induce Cyclooxygenase 1 Expression in Cardiomyocytes: Role of Glucocorticoid Receptor and Sp3 Transcription Factor

Interdisciplinary Graduate Program of Pharmacology and Toxicology (H.S.) and Department of Pharmacology (E.S., Q.M.C.), University of Arizona, Tucson, Arizona 85724

Address all correspondence and requests for reprints to: Qin M. Chen, Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, Arizona 85724. E-mail: qchen{at}email.arizona.edu.

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 µM) 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.

NURSA Molecule Pages Link:

Nuclear Receptors:   GR

Ligands:   Dexamethasone  |  RU486

This article has been cited by other articles:

				H. Sun, E. Sheveleva, B. Xu, H. Inoue, T. G. Bowden, and Q. M. Chen Corticosteroids induce COX-2 expression in cardiomyocytes: role of glucocorticoid receptor and C/EBP-{beta} Am J Physiol Cell Physiol, October 1, 2008; 295(4): C915 - C922. [Abstract] [Full Text] [PDF]