Gene/Protein
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Enzyme
Compound
Pivot Concepts:
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Target Concepts:
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Query: EC:3.1.26.9 (
ribonuclease
)
6,589
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Coordinated upregulation of the cardiac endothelin system in a rat model of heart failure. 959 63
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.
...
PMID:Increased cardiac and pulmonary endothelin-1 mRNA expression in canine pacing-induced heart failure. 959 2
We hypothesize that poly (ADP-ribosyl)ation, that is, poly (ADP-ribose) polymerase (PARP)-dependent transfer of ADP-ribose moieties from NAD to nuclear proteins, plays a role in diabetic nephropathy. We evaluated whether PARP activation is present and whether two unrelated PARP inhibitors, 3-aminobenzamide (ABA) and 1,5-isoquinolinediol (ISO), counteract overexpression of
endothelin-1
(
ET-1
) and ET receptors in the renal cortex in short-term diabetes. The studies were performed in control rats and streptozotocin-diabetic rats treated with/without ABA or ISO (30 and 3 mg x kg(-1) x day(-1), intraperitoneally, for 2 weeks after 2 weeks of diabetes). Poly (ADP-ribose) immunoreactivity was increased in tubuli, but not glomeruli, of diabetic rats and this increase was corrected by ISO, whereas ABA had a weaker effect.
ET-1
concentration (ELISA) was increased in diabetic rats, and this elevation was blunted by ISO.
ET-1
, ET(A), and ET(B) mRNA (
ribonuclease
protection assay), but not ET-3 mRNA (RT/PCR), abundance was increased in diabetic rats, and three variables were, at least, partially corrected by ISO. ABA produced a trend towards normalization of
ET-1
concentration and
ET-1
, ET(A), and ET(B) mRNA abundance, but the differences with untreated diabetic group were not significant. Poly(ADP-ribosyl)ation is involved in diabetes-induced renal overexpression of
ET-1
and ET receptors. PARP inhibitors could provide a novel therapeutic approach for diabetic complications including nephropathy, and other diseases that involve the endothelin system.
...
PMID:Diabetes-induced overexpression of endothelin-1 and endothelin receptors in the rat renal cortex is mediated via poly(ADP-ribose) polymerase activation. 1282 90
Pulmonary hypertension associated with human immunodeficiency virus (HIV) infection also involves injury to the lung endothelium. However, the pathogenesis of HIV-induced pulmonary hypertension is not known; we hypothesized that HIV or secreted viral proteins could play a role in vascular injury and the increased frequency of pulmonary hypertension observed in HIV-infected patients. Here, we report that exposure of HIV-1 gp120 proteins to primary human lung microvascular endothelial cells causes apoptosis, as assessed by TUNEL assay, Annexin-V staining, and DNA laddering. Using
ribonuclease
protection assay and Western blotting we find that gp120-induced apoptosis of lung endothelial cells involves a down-regulation in Bcl-xl mRNA and proteins. In addition, gp120 significantly increases secretion of the potent vasoconstrictor
endothelin-1
by human lung endothelial cells. These data suggest that secreted HIV gp120 proteins induce lung endothelial cell injury and could contribute to the development of HIV-associated pulmonary hypertension.
...
PMID:Induction of apoptosis and endothelin-1 secretion in primary human lung endothelial cells by HIV-1 gp120 proteins. 1597 50
