Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Superoxide anions (O(*-)(2)) induce oxidative stress and reduce endothelial NO availability by peroxynitrite formation. In human endothelial cells gp91(phox) was identified as the limiting subunit of the forming NAD(P)H oxidase. Because endothelin-1 (ET-1) is considered as a pro-atherosclerotic stimulus, we analyzed the effect of ET-1 on gp91(phox) expression and O(*-)(2) generation in primary cultures of human umbilical vein endothelial cells (HUVECs). The gp91(phox) mRNA expression was quantified by standard calibrated competitive reverse transcriptase-polymerase chain reaction. ET-1 induces gp91(phox) mRNA expression in HUVEC (max. after 1 h). The induction of gp91(phox) expression was dose-dependent, reaching its maximum at 10 nmol/L ET-1. The increased gp91(phox) expression is mediated by endothelial receptor type B (ET(B)). Furthermore, ET-1 augments O(*-)(2) generation in human endothelial cells as measured by coelenterazine chemiluminescence. These data support a new mechanism: how ET-1 increases oxidative stress in the vessel wall leading to endothelial dysfunction and enhanced susceptibility to atherosclerosis.
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PMID:Endothelin-1 induces NAD(P)H oxidase in human endothelial cells. 1072 Apr 82

The endothelial cell-derived endothelin-1 (ET-1) is a potent mitogen for endothelial cells, vascular smooth muscle cells, and tumor cells. In this study, we analyzed the role of ET-1 on human umbilical vein endothelial cell (HUVEC) phenotype related to different stages of angiogenesis. ET-1 promoted HUVEC proliferation, migration, and invasion in a dose-dependent manner. The ET(B) receptor (ET(B)R) antagonist, BQ 788, blocked the angiogenic effects induced by ET-1, whereas the ET(A)R antagonist was less effective. ET-1 stimulated matrix metalloproteinase-2 mRNA expression and metalloproteinase-2 production, as determined by reverse transcriptase-polymerase chain reaction and gelatin zymography. Furthermore ET-1 was able to enhance HUVEC differentiation into cord vascular-like structures on Matrigel. When tested in combination with vascular endothelial growth factor (VEGF), ET-1 enhanced VEGF-induced angiogenic-related effects on endothelial cells in vitro. Finally, using the Matrigel plug neovascularization assay in vivo, ET-1 in combination with VEGF stimulated an angiogenic response comparable to that elicited by basic fibroblast growth factor. These findings demonstrated that ET-1 induces angiogenic responses in cultured endothelial cells through ET(B)R and that stimulates neovascularization in vivo in concert with VEGF. ET-1 and its receptors acting as angiogenic regulators might represent new targets for anti-angiogenic therapy.
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PMID:Endothelin-1 induces an angiogenic phenotype in cultured endothelial cells and stimulates neovascularization in vivo. 1107 29

We established a real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR) system for the analysis of rat endothelin-1 (ET-1) and vasoactive intestinal contractor (VIC)/ET-2 gene expression. We used this technique to examine the expression levels in rat in 16 different organs. ET-1 gene expression was observed in all organs examined, while VIC mRNA was detected in some organs such as heart, lung, ovary, stomach, and intestine. Ovary and intestine express both ET-1 and VIC mRNA at high levels, suggesting the importance of both peptides in these organs. In addition, we examined the gene expression levels in intestinal epithelial and mesenchymal tissues from rat fetuses at 16.5 and 19.5 days postcoitus (E16.5 and E19.5). We observed distinct differences in the temporal gene expression patterns for ET-1 and VIC in fetal intestinal epithelial tissue. In fetal mesenchymal tissue the expression level of ET-1 is significantly higher than that of VIC, and the levels of both genes remain unchanged over the time period observed. These findings suggest distinct biological roles and gene regulation mechanisms for ET-1 and VIC in intestinal epithelial and mesenchymal tissues.
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PMID:Quantitative analysis of endothelin-1 and vasoactive intestinal contractor/endothelin-2 gene expression in rats by real-time reverse transcriptase polymerase chain reaction. 1107 20

Although evidence has been accumulated to support a role of endothelin-1 (ET-1) in cardiac hypertrophy, details of the pathophysiological significance of ET-1 in cardiac hypertrophy remain to be elucidated. In the present study, we investigated the effects of the vasodilator hydralazine on the blood pressure, cardiac hypertrophy and ET-1 gene expression in various tissues of spontaneously hypertensive rats (SHR-SP/Izm). Hydralazine (20 mg/kg/day) was administered orally from the age of 4 weeks for 8 weeks. Tissues of the kidney, heart, aorta and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Administration of hydralazine resulted in a significant decrease in the blood pressure (156 +/- 1 mmHg vs 212 +/- 4 mmHg in controls) and an increase in the heart rate (470 +/- 20 bpm vs 402 +/- 23 bpm in controls). ET-1 mRNA expression was significantly decreased in the heart (x 1/2), kidney (x 1/4) and brain (x 1/2). There was no significant change of the cardiac weight (309 +/- 4 mg/100 g body weight vs 307 +/- 5 mg/100 g body weight in controls). The dissociation between ET-1 mRNA expression and cardiac hypertrophy in hydralazine-treated rats may suggest that the increased tissue ET-1 is not an indispensable factor of cardiac hypertrophy in hypertension. Sympathetic activation, as shown by the reactive tachycardia, may overcome the effects on the blood pressure and ET-1 expression.
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PMID:Hydralazine decreases blood pressure and endothelin-1 mRNA expression in tissues but not cardiac weight in SHR-SP/Izm rats. 1107 70

Recent studies revealed important roles for endothelin-1 (ET-1) in the pathogenesis of hypertension. Whether ET-1 could be a primary cause of hypertension or a secondary factor associated with hypertension, however, remains unknown. In this study, we determined plasma ET-1 levels and the expression of ET-1 mRNA in tissues of rats rendered hypertensive using distinct mechanisms: deoxycorticosterone acetate (DOCA)-salt hypertension: N(G)-nitro-L-arginine-methyl ester- (L-NAME) induced hypertension; and spontaneously hypertensive rats (SHR-SP). ET-1 mRNA expression level was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blotting. There was no significant difference in plasma ET-1 levels between the hypertensive rats and normotensive rats. By contrast, ET-1 mRNA level was significantly increased in various tissues including the adrenal, lung, kidney and brain of these hypertensive rats compared with control rats. Thus, ET-1 gene expression was ubiquitously augmented in tissues of hypertensive rats irrespective of the cause of the hypertension. The results suggest that the increase in ET-1 expression is not the primary cause of hypertension but a secondary outcome which may further exacerbate the hypertension.
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PMID:Augmented expression of tissue endothelin-1 messenger RNA is a common feature in hypertensive rats. 1107 75

Although smoking has been suggested to be involved in the development of cardiovascular diseases, details of the mechanism still need to be revealed. We investigated the effects of cigarette smoking on the tissue mRNA expression of endothelin-1 (ET-1). Male Wistar rats of 4 weeks of age were exposed to smoke from six cigarettes for 30 min (acute exposure) and six cigarettes for 30 min/day, 5 days a week for 6 months (chronic exposure). Half of the rats exposed to 6 months smoking were kept in clean-air conditions for a further 3 months to clear the effects. Tissue expression of ET-1 mRNA in the kidney, aorta, heart and lung was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. There was no significant difference in body and organ weight of the heart and kidney between the control and smoking group in either the acute or chronic experiment. In the acute-exposure experiment, expression of ET-1 mRNA was increased in the heart and lung, while that in the kidney and aorta was unchanged. In the chronic-exposure experiment, however, there was no significant difference in the expression of ET-1 mRNA in all the tissues between the smoking and control groups. These results suggest that cigarette smoking could cause cardiovascular and pulmonary diseases by modulating ET-1 mRNA expression in the tissues.
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PMID:Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissues in rats. 1107 76

We have demonstrated previously that endothelin-1 (ET-1) mRNA expression is increased in hypertensive rats. The aim of the study reported here was to elucidate the effects of the endothelin (ET) receptor antagonist on the hemodynamic and biochemical parameters in stroke-prone spontaneously hypertensive rats (SHRSPs/Izm). The endothelin-A- and -B- (ETA/ETB) receptor antagonist (TAK-044, Takeda Chemical Industries, Osaka, Japan) was administered subcutaneously at a dose of 10 mg/kg/day from the age of 8 weeks for 4 weeks. Blood samples and tissues of the kidney, heart and brain were obtained at the age of 12 weeks. Tissue expression of ET-1 mRNA was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. Treatment with TAK-044 resulted in a significant decrease in systolic blood pressure (SBP), blood urea nitrogen (BUN), serum creatinine concentration, plasma aldosterone level, heart weight, and kidney weight. In addition, ET-1 contents and mRNA expression level in the kidney, heart and brain were significantly decreased by the treatment with TAK-044. These results suggest that the ET receptor antagonist TAK-044 is able to attenuate ET-1 gene expression in addition to its specific antagonism of the biological actions of ET via the receptors.
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PMID:Hemodynamic and biochemical effects of endothelin-A- and -B-receptor antagonist TAK-044 in stroke-prone spontaneously hypertensive rats. 1107 13

Production and secretion of endothelin-1 (ET-1) by a human glioblastoma cell line, T98G, were studied by radioimmunoassay and Northern blot analysis. Immunoreactive ET was detected in the culture medium of T98G (17.6 +/- 0.6 fmol/10(5) cells/24 h, mean +/- SEM, n = 5). Reverse-phase high-performance liquid chromatography (HPLC) of immunoreactive ET in the culture medium extract showed a single peak eluting in the position of ET-1. Northern blot analysis showed expression of ET-1 mRNA in T98G cells. Treatment with interferon-gamma decreased the expression of ET-1. Treatment with TNFalpha or interleukin-1beta (IL-1beta) increased the expression of ET-1. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) showed expression of endothelin-A- and -B- (ET(A) and ET(B)) receptor mRNAs in T98G glioblastoma cells. These findings indicate that glioblastoma cells produce and secrete ET-1, and express ET receptor mRNAs. ET-1 secreted by glioblastoma cells may act locally on tumor cells, possibly as a growth modulator.
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PMID:Expression of endothelin-1 and endothelin receptors in cultured human glioblastoma cells. 1107 29

Little is known about the mechanism(s) underlying hyperpigmentation in lentigo senilis. We have previously reported that keratinocyte-derived endothelins are intrinsic paracrine mitogens and melanogens for human melanocytes and that they play an essential role in stimulating ultraviolet-B-induced melanogenesis. In this study, we have used immunohistochemistry and reverse transcriptase polymerase chain reaction analysis to clarify the role of the endothelin cascade, including endothelin production, processing by endothelin-converting enzyme, and expression of the endothelin B receptor, in the hyperpigmentary mechanism(s) involved in lentigo senilis. The number of tyrosinase immunopositive melanocytes in lentigo senilis lesional skin was increased 2-fold over the perilesional epidermis. Immunohistochemistry using antibodies to endothelin-1 demonstrated relatively stronger staining in the lesional epidermis than in the perilesional epidermis. Reverse transcriptase polymerase chain reaction analysis concomitantly demonstrated accentuated expression of transcripts for endothelin-1 and for the endothelin B receptor in lentigo senilis lesional skin, which was accompanied by a similar accentuated expression of tyrosinase mRNA compared with the perilesional control. The endothelin-1-inducible cytokine, tumor necrosis factor alpha, was consistently upregulated in the lentigo senilis lesional epidermis as determined at the transcriptional level and by immunostaining, whereas interleukin-1alpha was downregulated. In contrast, endothelin-converting enzyme 1alpha mRNA was not substantially increased in the lesional epidermis. These findings suggest that an accentuation of the epidermal endothelin cascade, especially with respect to expression of endothelin and the endothelin B receptor, plays an important role in the mechanism involved in the hyperpigmentation of lentigo senilis.
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PMID:The role of the epidermal endothelin cascade in the hyperpigmentation mechanism of lentigo senilis. 1128 25

Polymorphonuclear neutrophils (PMNs) are only regarded as being involved in the cleavage of exogenous big endothelin-1 (ET-1) to the active peptide. The aims of the present study were to investigate whether PMNs may themselves express mRNA for prepro-ET-1 (pp-ET-1, a long precursor of 212 amino acids) and to determine the capacity of several PMN stimulants to modulate mRNA expression and the release of ET-1 in culture medium. PMNs, isolated from seven healthy adult volunteers, were stimulated with lipopolysaccharide (LPS, 0.25-10 microg/ml), or LPS (1 microg/ml) + phorbol myristate acetate (PMA, 10 ng/ml) or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (f-MLP, 10(-5) M) or tumour necrosis factor-alpha (TNF-alpha, 50 IU/ml). They were found to express pp-ET-1 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Enzyme immunoassay (EIA) revealed low levels of ET-1 in the culture supernatants of PMNs stimulated for 3 h with LPS (10 microg/ml) and with LPS + PMA. Control unstimulated PMNs did not express pp-ET-1 mRNA. The local production of ET-1 by PMNs in vivo has significant implications in inflammatory diseases.
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PMID:Gene expression of endothelin-1 (ET-1) and release of mature peptide by activated human neutrophils. 1144 23


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