Human-Antigen R (HuR) Expression in Hypertension
| Autor: | Stephan Klöss, Daniela Rodenbach, Reingart Bordel, Alexander Mülsch |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Electrophoresis
Male Aging medicine.medical_specialty RNA Stability Down-Regulation In Vitro Techniques Rats Inbred WKY ELAV-Like Protein 1 Downregulation and upregulation Rats Inbred SHR Internal medicine Internal Medicine medicine Animals Protein Isoforms RNA Messenger Receptor 3' Untranslated Regions Aorta Regulation of gene expression Messenger RNA Tissue Extracts business.industry Binding protein RNA-Binding Proteins RNA Recombinant Proteins Rats B vitamins Endocrinology ELAV Proteins Solubility Guanylate Cyclase Antigens Surface Chronic Disease Hypertension cardiovascular system Soluble guanylyl cyclase business |
| Zdroj: | Hypertension. 45:1200-1206 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/01.hyp.0000165674.58470.8f |
| Popis: | In aged spontaneously hypertensive rats (SHR), vasorelaxant responses to NO are attenuated compared with normotensive control rats (Wistar-Kyoto [WKY]) because of a decreased expression of the important NO receptor soluble guanylyl cyclase (sGC). Because the expression of sGC subunits α 1 and β 1 is controlled at the post-transcriptional level by the mRNA-binding protein human-antigen R (HuR), we now assessed whether or not altered expression of HuR could account for downregulation of sGCα 1 and sGCβ 1 in genetic hypertension. The expression of HuR (and sGCα 1 and sGCβ 1 ) in aortas from aged SHR was significantly decreased at the mRNA and protein level compared with age-matched WKY rats, whereas expression of HuR was not different in prehypertensive young (2 months of age) SHR and age-matched WKY rats. The mRNA-binding activity of HuR in native aortic protein extracts from aged SHR was markedly reduced compared with normotensive WKY rats, as detected by RNA electrophoretic mobility shift analysis, using biotin-labeled adenine and uracil (AU)–rich element (ARE)–containing RNA probes from the 3′-untranslated region of sGCα 1 and sGCβ 1 . In contrast, ARE-binding activity was not different between prehypertensive young SHR and young WKY rats. In vitro RNA degradation assays using the same AU-rich sGC mRNA probes revealed an accelerated sGCα 1 and sGCβ 1 mRNA decay in the presence of native protein extract from hypertensive SHR, which was less rapid with aortic protein from normotensive WKY rats. These findings suggest that in this animal model of genetic hypertension, the reduced expression of sGC subunits is mediated by downregulation of the sGC mRNA–stabilizing protein HuR. |
| Databáze: | OpenAIRE |
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