Endothelial Cytosolic Proteins Bind to the 3′ Untranslated Region of Endothelial Nitric Oxide Synthase mRNA: Regulation by Tumor Necrosis Factor Alpha

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Abstract
Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 39 untranslated region (39 UTR). A U+C-rich segment in the 39 UTR is critical in complex formation with bovine aortic endothelial cell cytosolic proteins. Tumor necrosis factor alpha (TNF-alpha), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner. These data suggest that endothelial cytosolic proteins bind to the 39 UTR of eNOS mRNA. These proteins may play a role in TNF-alpha-induced eNOS mRNA destabilization.