Corticosteroids induce cyclooxygenase 1 expression in cardiomyocytes

Role of glucocorticoid receptor and Sp3 transcription factor

Haipeng Sun, Elena Sheveleva, Qin Chen

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)2076-2084
Number of pages9
JournalMolecular Endocrinology
Volume22
Issue number9
DOIs
StatePublished - Sep 2008

Fingerprint

Sp3 Transcription Factor
Cyclooxygenase 1
Glucocorticoid Receptors
Cardiac Myocytes
Adrenal Cortex Hormones
Corticosterone
Genes
Sp Transcription Factors
Mifepristone
Sequence Deletion
Chromatin Immunoprecipitation
Gene Deletion
Prostaglandin-Endoperoxide Synthases
Small Interfering RNA
Transcriptional Activation
Glucocorticoids
Prostaglandins

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Corticosteroids induce cyclooxygenase 1 expression in cardiomyocytes : Role of glucocorticoid receptor and Sp3 transcription factor. / Sun, Haipeng; Sheveleva, Elena; Chen, Qin.

In: Molecular Endocrinology, Vol. 22, No. 9, 09.2008, p. 2076-2084.

Research output: Contribution to journalArticle

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