Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Editor

Personal info

View

About

Terms

Javascript disabled

Please enable Javascript support in your browser to use this application.

Instructions on how to enable JavaScript on different browsers can be found here: http://www.google.com/support/bin/answer.py?answer=23852.

[edit this page]

Martínez-González, J. et al.

3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition prevents endothelial NO synthase downregulation by atherogenic levels of native LDLs: balance between transcriptional and posttranscriptional regulation.

Atherogenic levels of native low density lipoproteins (nLDLs) decrease the bioavailability of endothelium-derived NO and downregulate endothelial NO synthase (eNOS) expression in cultured human endothelial cells. Here, we show that simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, within the therapeutic range (0.01 to 1 micromol/L) prevented the downregulation of eNOS mRNA and protein promoted by nLDL (180 mg cholesterol/dL, 48 hours) in human umbilical vein endothelial cells. This effect of simvastatin was completely reversed by mevalonate, the product of the reaction, and to a lesser extent by farnesol and geranyl geraniol. Simvastatin significantly stabilized eNOS mRNA in cells treated with nLDL during 48 hours (eNOS mRNA half-life approximately 11 hours in controls versus >24 hours in nLDL per 0.1 micromol/L simvastatin-treated cells). The downregulation of eNOS by nLDL was abrogated by cycloheximide, an inhibitor of protein synthesis, and by N-acetyl-leucyl-leucyl-norleucinal, a protease inhibitor that reduces the catabolism of sterol regulatory element binding proteins. Sterol deprivation increased the downregulation produced by nLDL on eNOS and sterol regulatory element binding protein-2 expression levels. However, no differential modulation of the retardation bands corresponding to the putative sterol-responsive element present in the eNOS promoter was detected by electrophoretic mobility shift assay. Our results suggest that nLDL promote eNOS downregulation operating at a transcriptional level, whereas simvastatin prevents such an effect through a posttranscriptional mechanism.[1]

References

3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition prevents endothelial NO synthase downregulation by atherogenic levels of native LDLs: balance between transcriptional and posttranscriptional regulation. Martínez-González, J., Raposo, B., Rodríguez, C., Badimon, L. Arterioscler. Thromb. Vasc. Biol. (2001) [Pubmed]

Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenes Open Access Licence Privacy Policy Terms of Use apsburg

The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.