RGD Reference Report - Inhibitors of GSK-3 prevent corticosterone from inducing COX-1 expression in cardiomyocytes. - Rat Genome Database

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

Authors: Sun, H  Chen, QM 
Citation: Sun H and Chen QM, Cardiovasc Toxicol. 2008 Summer;8(2):93-100. Epub 2008 Jun 27.
RGD ID: 2300226
Pubmed: PMID:18584335   (View Abstract at PubMed)
DOI: DOI:10.1007/s12012-008-9018-y   (Journal Full-text)

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-3beta increased COX-1 promoter activity, which was abolished by LiCl. LiCl increased inhibitory GSK-3alpha/beta phosphorylation at Ser21/Ser9, while BIO or SB216763 prevented stimulatory phosphorylation at Tyr279/Tyr216 of GSK-3alpha/beta. 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to corticosterone  IEP 2300226 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs1  (prostaglandin-endoperoxide synthase 1)


Additional Information