Dual Effects of Histone Deacetylase Inhibition by Trichostatin A on Endothelial Nitric Oxide Synthase Expression in Endothelial Cells.
From: Laboratory of Molecular Biology and Center for TMJ Disorders, Peking University School of Stomatology, Beijing 100081, China.
Biochemical and biophysical research communications
- Publish Date: Feb 2006
- ISSN: 0006-291X
- Volume: 340
- Issue: 1
- Pages: 29-34
- Medium: Print
- Language: English
- Citation (JAMA): Gan Yehua, Shen Ying H, Utama Budi, et al. Dual Effects of Histone Deacetylase Inhibition by Trichostatin A on Endothelial Nitric Oxide Synthase Expression in Endothelial Cells.. Biochem. Biophys. Res. Commun. Feb 2006;340:29-34
Abstract
Inhibition of histone deacetylases by trichostatin A (TSA) has pleiotropic effects on gene expression. We demonstrated that at low dose (0.1 microg) TSA increased the eNOS mRNA levels, which was followed by a time- and dose-dependent down-regulation. Cycloheximide, a protein synthesis inhibitor, completely abolished TSA-induced decrease in eNOS expression, indicating that new protein synthesis is required for the inhibiting effect. Mevastatin — an inhibitor HMG-CoA reductase and geranylgeranylation reaction dose-dependently antagonized TSA-induced reduction. This mevastatin-mediated antagonism was completely abolished by geranylgeranylpyrophosphate, suggesting that geranylgeranyl modification is needed to activate the eNOS mRNA destabilizing factor — a mechanism responsible for statin-mediated eNOS upregulation.
Mesh Headings (Keywords): Cells, Cultured, Dose-Response Relationship, Drug, Endothelial Cells, Gene Expression Regulation, Enzymologic, Histone Deacetylases, Humans, Hydroxamic Acids, Nitric Oxide Synthase Type III
Check for Full Text / PubMed Unique Identifier (PMID): 16338217
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