Inhibitors of GSK-3 prevent corticosterone from inducing COX-1 expression in cardiomyocytes

Haipeng Sun, Qin Chen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Our recent study has demonstrated that glucocorticoids (GCs) induce cyclooxygenase-1 (COX-1) gene expression in rat cardiomyocytes. While investigating the mechanism underlying corticosterone (CT) induced COX-1, we found that three structurally and mechanistically distinct GSK-3 inhibitors, LiCl, SB216763, and (2′Z,3′E)-6-Bromoindirubin-3′-oxime (BIO), inhibited COX-1 transcription and protein induction. A genetic approach of expressing wild type GSK-3β increased COX-1 promoter activity, which was abolished by LiCl. LiCl increased inhibitory GSK-3α/β phosphorylation at Ser21/Ser9, while BIO or SB216763 prevented stimulatory phosphorylation at Tyr279/Tyr216 of GSK-3α/β. GSK inhibitors failed to block nuclear translocation of glucocorticoid receptor (GR) or activation of glucocorticoid response element (GRE) by CT treatment. While Sp3 transcription factor mediates CT induced COX-1 expression, GSK inhibitors did not change the level of Sp3 protein or binding of Sp3 transcription factor to COX-1 promoter. The observed effect of GSK-3 inhibitors appears to be unique to COX-1 since LiCl or BIO does not prevent CT from inducing COX-2 gene. We conclude that GSK-3 inhibitors block CT from inducing COX-1 gene expression via a mechanism beyond GR and Sp3 transcription factor.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalCardiovascular Toxicology
Volume8
Issue number2
DOIs
StatePublished - Jun 2008

Fingerprint

Glycogen Synthase Kinase 3
Cyclooxygenase 1
Corticosterone
Cardiac Myocytes
Sp3 Transcription Factor
Phosphorylation
Glucocorticoid Receptors
Gene expression
Glucocorticoids
Gene Expression
Response Elements
Transcription
Protein Binding
Rats
Proteins
Genes
Chemical activation

Keywords

  • Corticosteroids
  • Cyclooxygenase
  • Glycogen synthase kinases
  • Pharmacological inhibitors
  • Transcription

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Cite this

Inhibitors of GSK-3 prevent corticosterone from inducing COX-1 expression in cardiomyocytes. / Sun, Haipeng; Chen, Qin.

In: Cardiovascular Toxicology, Vol. 8, No. 2, 06.2008, p. 93-100.

Research output: Contribution to journalArticle

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