Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.27.1 (RNase)
16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for endothelin in malignant phase hypertension has been suggested on the basis of reported increases of circulating plasma immunoreactive endothelins in animal models. Recently, a hypertensive rat model that exhibits a genetically determined tendency for developing spontaneous onset malignant hypertension has been described. Expression of the three genes endothelin-1, endothelin-2, and endothelin-3 was quantified in the kidney by specific RNase protection assays in rats with established malignant hypertension, in rats with benign hypertension with and without a genetic susceptibility to malignant hypertension, and in normotensive Sprague-Dawley rats. Endothelin-1 mRNA levels were significantly elevated in the group with malignant hypertension compared with the other three groups. For determination of whether endothelin-1-mediated effects were crucial in the transition from benign to malignant phase hypertension, an oral nonspecific combined endothelin-A and endothelin-B receptor antagonist (bosentan) was given to hypertensive rats susceptible to malignant hypertension. No hypotensive effects were observed, and no significant difference in the incidence of malignant hypertension was observed between treated and control groups. In conclusion, although increased endothelin-1 mRNA expression was found in kidney tissue from rats developing malignant hypertension, blockade of endothelin-1-mediated effects did not prevent the transition from benign phase hypertension. Hence, increased renal endothelin-1 expression in this model of malignant hypertension does not appear to have a causative role and may simply reflect cellular damage and ischemia.
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PMID:Endothelin in the kidney in malignant phase hypertension. 749 Jan 50

Persistent infections of C6 rat astrocytoma cells with measles (subacute sclerosing panencephalitis [SSPE]) virus (C6/SSPE cells) or canine distemper virus (C6/CDV cells) cause a loss of endothelin-1 (ET-1) binding to its specific receptors (ETRA type) and subsequent ET-1-induced Ca2+ signaling. It was the aim of this study to investigate the underlying mechanism of this phenomenon in more detail. By using an RNase protection assay, it was found that ETRA mRNA disappears, whereas other cellular mRNA species, e.g., beta-actin mRNA, were not influenced. The data show that the loss of the ET-1 signaling pathway in C6/SSPE and C6/CDV cells is due to a receptor downregulation at the transcriptional level.
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PMID:Downregulation of endothelin receptor mRNA synthesis in C6 rat astrocytoma cells by persistent measles virus and canine distemper virus infections. 760 93

Circulating endothelin-1 concentrations are elevated in animal models of sepsis. The major actions of endothelin-1 appear to be as a local autocrine and paracrine factor, rather than as a circulating hormone, and plasma concentrations may not reflect local tissue concentrations. We therefore measured tissue expression of mRNA encoding pre-pro-endothelin-1 by RNase protection assays, as an indicator of local production of ET-1 in an in vivo rat model of endotoxaemia. The effects of dexamethasone pre-treatment were also examined. There was a tissue-specific increase in pre-pro-endothelin-1 mRNA in endotoxaemia, apparent at 6h after endotoxin challenge in heart and lung. No significant changes in expression were seen in kidney or skeletal muscle. Dexamethasone pre-treatment significantly attenuated the rise in pre-pro-endothelin-1 mRNA in heart at 6h. Therefore, we have demonstrated tissue-specific differences in the effect of endotoxin upon pre-pro-endothelin-1 mRNA expression and in sensitivity to dexamethasone. This could account for some of the inter-tissue differences seen in local vascular response to endotoxin.
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PMID:Tissue expression of endothelin-1 mRNA in endotoxaemia. 857 67

To elucidate the regulation of very-low density-lipoprotein (VLDL) receptor, we have studied its gene expression in the heart of spontaneously hypertensive rats-stroke prone (SHR-SP, an animal model for hypertension-induced cardiac hypertrophy) compared with Wistar-Kyoto rats. RNase protection assay showed that ventricular VLDL receptor mRNA falls to 41% of normal levels at 4 weeks when hypertension is not yet fully developed, and drops further to 14% at 13 weeks, when cardiac hypertrophy is established. Lipoprotein lipase mRNA decreases in parallel with VLDL receptor mRNA. In cultured neonatal rat ventricular cardiomyocytes, VLDL receptor mRNA decreases in parallel with the process of cardiocyte hypertrophy during the 24 hours after treatment with 10-8 mol/L endothelin-1, falling to 40% of the initial value. These results demonstrate that there is downregulation of VLDL receptor gene expression in cardiac hypertrophy both in vivo and in vitro and suggest that the regulation of the VLDL receptor is possibly linked with the switch in energy substrate from lipid to glucose known to occur in cardiac hypertrophy.
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PMID:Regulation of very-low-density lipoprotein receptor in hypertrophic rat heart. 860 9

The three cloned alpha1-adrenergic receptor (AR) subtypes, alpha1B, alpha1C, and alpha1D, can all couple to the same effector, phospholipase C, and the reason(s) for conservation of multiple subtypes remain uncertain. All three alpha1-ARs are expressed natively in cultured neonatal rat cardiac myocytes, where chronic exposure to the agonist catecholamine norepinephrine (NE) induces hypertrophic growth and gene transcription. We show here, using RNase protection, that the alpha1-AR subtype mRNAs respond in distinctly different ways during prolonged NE exposure (12 72 h). Alpha1B and alpha1D mRNA levels were repressed by NE, whereas alpha1C mRNA was induced. Changes in mRNA levels were mediated by an alpha1-AR, were not explained by altered mRNA stability, and were reflected in receptor proteins by [3H]prazosin binding. alpha1-AR-stimulated phosphoinositide hydrolysis and myocyte growth were not desensitized. Three other hypertrophic agonists in culture, endothelin-1, PGF2alpha, and phorbol 12-myristate 13-acetate, also induced alpha1C mRNA and repressed alpha1B mRNA. In myocytes from hearts with pressure overload hypertrophy, alpha1 mRNA changes were identical to those produced by NE in culture. These results provide the first example of a difference in regulation among alpha1-AR subtypes expressed natively in the same cell. Transcriptional induction of the alpha1C-AR could be a mechanism for sustained growth signaling through this receptor and is a common feature of a hypertrophic phenotype in cardiac myocytes.
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PMID:Alpha1-adrenergic receptor subtype mRNAs are differentially regulated by alpha1-adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo. Repression of alpha1B and alpha1D but induction of alpha1C. 862 54

The effects of mycoplasma infection on the biosynthesis of endothelin-1 (ET-1) in cultured human vascular endothelial cell lines were examined to understand regulatory mechanisms of ET-1 biosynthesis and causes of angiopathy due to mycoplasma infection. The growth of normal endothelial cells from the umbilical cord vein and of an immortal endothelial cell line transfected with prepro ET-1 cDNA was decreased, while the secretion of ET-1 into the culture medium was enhanced by mycoplasma infection. However, the rate of ET-1 production in these cell cultures was much higher at the growing phase than at the stationary phase. Immunocytochemical studies with anti-ET-1 antibody and an autoradiographic examination of the labeled nuclei with 3H-TdR revealed that mycoplasma infection induced an elevation of ET-1 production in both S and non-S phase cells. The expression of prepro ET-1 mRNA as examined by in situ hybridization and by RNase protection assay was not altered by mycoplasma infection. Thus, the biosynthesis of ET-1 in vascular endothelial cells may be regulated at the posttranscriptional level.
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PMID:Elevation of endothelin biosynthesis in human endothelial cells with mycoplasma infection. 882 94

The aim of the present study was to test the hypothesis that the vasoconstrictive peptide endothelin-1 is upregulated in ischemia and reperfusion in skeletal muscle. Sixty-eight Wistar rats were included in the series: 12 served as controls that did not undergo the procedure, 16 underwent sham operations, and 40 were subjected to a modified tourniquet ischemia for 3 hours and 20 minutes. Of the 40 rats, 16 were killed at the end of the ischemic period, 16 underwent reperfusion for 2 hours, and eight underwent reperfusion for 72 hours. Areas of necrosis were measured by morphometry in hematoxylin and eosin-stained cross sections of the anterior tibial muscles that had been reperfused for 72 hours. Sections from the controls, the muscles that had not been reperfused, and the reperfused muscles were immunostained for endothelin-1. Serum endothelin-1 levels in blood samples from the aorta were determined with a commercial enzyme immunoassay kit. The anterior tibial muscle was harvested for preproendothelin-1 mRNA analysis with RNase protection assay. The hematoxylin and eosin-stained sections showed extensive necrosis with an acellular core of no reperfusion. The muscular core demonstrated weak immunostaining for endothelin-1 in all sections, a subfascial narrow brim of fibers showed enhanced immunoreactivity at the end of ischemia, and all fibers outside the core stained by 2 hours after the start of reperfusion. After 72 hours of reperfusion, the fibers outside the core stained positive in a checkerboard-like pattern. There were no differences in serum endothelin-1 levels between the groups. Preproendothelin-1 mRNA analysis with RNase protection assay showed 2-fold upregulation at the end of ischemia and 4-fold upregulation after 2 hours of reperfusion (p = 0.001). This study supports the hypothesis that both ischemia and reperfusion upregulate endothelin-1 in skeletal muscle.
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PMID:Endothelin-1 is upregulated during skeletal muscle ischemia and reperfusion. 956 85

The potent vascular, cardiac, and renal actions of endothelin-1 (ET-1) suggest a role for this vasoconstrictor peptide in the pathophysiology of heart failure (HF). Recent studies have shown increased levels of ET-1 peptide accompanied by increased ETB receptor binding in the left ventricle during experimental HF. However, much less is known about the regulation of mRNA expression of these genes in HF. We compared the levels of mRNA expression for ET-1 and ET receptors (ETA and ETB) in the left ventricle of rats with HF induced by coronary artery ligation (n = 6) vs. sham-operated animals (n = 6). Levels of mRNA for ET-1 were determined by ribonuclease protection assay (RPA) using beta-actin as the internal control, whereas ET receptors were quantified by quantitative-competitive RT-PCR. Compared with sham animals, ET-1, ETA, and ETB receptor mRNA levels were markedly upregulated in the left ventricle by 6.6 +/- 1.8-fold (p < 0.01), 3.2 +/- 0.6-fold (p < 0.05), and 3.5 +/- 1.0-fold (p < 0.05), respectively. ET-1 mRNA levels were measured in two additional groups of rats (HF and sham; n = 6 each) treated for 4 weeks with the selective ETA receptor antagonist LU135252. This treatment had no significant effect on ET-1 mRNA expression in sham animals but reduced the upregulation of ET-1 expression in the HF group by 41 +/- 19% (p < 0.05). This study confirms the potential importance of ET-1 in HF and suggests that increased expression of ET-1 and ET receptors in the failing ventricle may contribute to alteration in basal cardiac contractility and myocardial remodeling.
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PMID:Coordinated upregulation of the cardiac endothelin system in a rat model of heart failure. 959 63

We studied target organ-protective effects of aracepril, an angiotensin-converting enzyme inhibitor, and the expression of endothelin-1 (ET-1) and nitric oxide synthase (NOS) mRNA. Aracepril (30 mg/kg) was administered orally to Izumo strain of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) for 8 weeks from 4 weeks of age and for 4 weeks from 8 weeks of age. The expression of ET-1 and endothelial NOS (eNOS) mRNA in the heart, aorta, kidneys, and brain cortex, and the expression of neuronal NOS (bNOS) mRNA in brain cortex, were analyzed by RT-PCR/Southern blotting or RNase protection analysis. Administration of aracepril markedly lowered blood pressure and decreased left ventricular weight in SHR-SP/Izm. Expression of ET-1 mRNA in the heart, kidneys, and brain was significantly enhanced in SHR/SP/Izm compared with that in WKY/Izm. Aracepril significantly decreased the expression of ET-1 mRNA, whereas there was no significant change of that in the aorta. Although expression of eNOS mRNA in the heart, aorta, and kidneys did not show any significant difference between the two strains of rats, administration of aracepril for 8 weeks significantly decreased the expression of eNOS and bNOS mRNA in brain tissue. These results suggested that aracepril may protect major target organs by modifying the expression of ET-1 and NOS mRNA, in addition to its hypotensive effect.
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PMID:Gene expression of endothelin-1 and endothelial-type nitric oxide synthase in cardiovascular tissues of stroke-prone spontaneously hypertensive rats/Izm: effects of the angiotensin-converting enzyme inhibitor aracepril. 959 94

The canine model of pacing-induced heart failure (HF) simulates human dilated cardiomyopathy and is characterized by severe hemodynamic perturbations. We have previously demonstrated increased plasma endothelin-1 (ET-1) and left ventricular (LV) tissue peptide levels in this model. However, the gene expression of ET-1 has not been studied. Accordingly, we compared preproET-1 mRNA in the lungs and LV in control normal dogs, dogs with severe HF after 3 weeks of rapid pacing (pHF), and pHF dogs chronically treated with an ETA antagonist, LU135252 (pHF-LU). PreproET-1 mRNA expression was determined by ribonuclease protection assay and quantified by densitometry. In paced dogs, mean pulmonary artery pressure (PA) and LV end-diastolic pressure (LVEDP) increased markedly from 16 +/- 4 and 8 +/- 3 mm Hg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mm Hg, respectively, at 3 weeks (both p < 0.001). Treatment with LU135252 attenuated the increase in PA and LVEDP by 30% and 19%, respectively (p < 0.05 for both). Compared to controls, preproET-1 mRNA expression in the LV and lungs was markedly increased in pHF. This was not changed in the LV but was reduced in the lungs by treatment with the ETA antagonist. Increased pulmonary and LV expression of preproET-1 suggests that ET-1 plays a role in mediating the pulmonary hypertension and LV dysfunction characteristic of this model.
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PMID:Increased cardiac and pulmonary endothelin-1 mRNA expression in canine pacing-induced heart failure. 959 2


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