Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angitensin system (RAS) plays an important role as a growth factor in cardiac development. Angiotensin converting enzyme is involved in converting angiotensin I to angiotensin II (Ag-II). The effects of Ag-II are mediated by two primary receptors, type 1 (AT1) and type 2 (AT2). Ag-II stimulates transforming growth factor-beta1(TGF-beta1) and acts as a potent stimulant of myocyte growth and fetal contractile protein gene transcription. The aim of this study was to determine the expression of Ag-II receptor subtypes and TGF-beta1 in the hypoplastic heart of nitrofen-induced congenital diaphragmatic hernia (CDH). CDH was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5. The fetuses were divided into three groups: normal controls (n=16), nitrofen-treated without CDH (n=16), and nitrofen-induced CDH (n=16). Reverse transcriptase-polymerase chain reaction was performed to evaluate mRNA expression of AT1, AT2, and TGF-beta1. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin. AT1 and AT2 mRNA expressions were significantly decreased in CDH heart compared with controls (0.43+/-0.33 vs. 1.0+/-0.48 and 0.62+/-0.23 vs. 1.4+/-0.43, respectively). TGF-beta1 mRNA expressions were also significantly decreased in CDH heart compared with controls (0.38+/-0.17 vs. 0.72+/-0.26). No significant difference was found between the hearts of controls and nitrofen-treated rats without CDH. The decreased expression of AT1, AT2, and TGF-beta1 mRNA in the hypoplastic heart suggests that the downregulation of RAS may be involved in the pathogenesis of cardiac hypoplasia in nitrofen-induced CDH.
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PMID:Altered expression of angiotensin II receptor subtypes and transforming growth factor-beta in the heart of nitrofen-induced diaphragmatic hernia in rats. 1557 92

The present study determined the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT1-R) antagonist losartan on the internal anal sphincter pressures (IASP) in spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats (WKY). The SHR had significantly higher IASP (21.7 +/- 0.8 mm Hg) than the WKY (14.7 +/- 0.9 mm Hg), which was associated with the higher levels of angiotensin II (Ang II) in plasma (50.3 +/- 0.9 pg/ml) and in muscle bath perfusates (72.7 +/- 11.8 pg/ml) compared with the WKY (p < 0.05). Captopril and losartan decreased the IASP in SHR and WKY, but they were more potent in SHR. Captopril and losartan normalized the IASP in the SHR, whereas these agents may compromise rectoanal continence in the WKY. Reverse transcriptase-polymerase chain reaction and Western blots showed higher levels of angiotensinogen, renin, ACE, and AT1-R in the internal anal sphincter (IAS) of SHR. Ang II caused concentration-dependent contraction of IAS smooth muscle strips from WKY (pEC50 = 8.5 +/- 0.1) and SHR (pEC50 = 8.6 +/- 0.2). Losartan (100 nM) significantly (p < 0.05) inhibited this effect. From these data, we conclude that 1) hypertensive IAS in SHR is primarily the result of renin-angiotensin system up-regulation, 2) ACE inhibitors and AT(1)-R antagonists simply relieve the hypertensive IAS, and 3) the differential effect of these inhibitors in the hypertensive versus the normotensive IAS may explain the lack of incontinence as a side effect in hypertensive patients receiving ACE inhibitors and AT1-R antagonists.
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PMID:Angiotensin-converting enzyme and angiotensin II receptor subtype 1 inhibitors restitute hypertensive internal anal sphincter in the spontaneously hypertensive rats. 1664 68

The development of nitrate tolerance has been found to be associated with vascular production of superoxide anion (O2-*), generated mainly by the eNOS and NADPH oxidase pathways. The aim of our study was to investigate whether long-term angiotensin-converting enzyme inhibition by ramipril is able to protect against nitrate tolerance in the aortas of eNOS-deficient (eNOS-/-) mice and to assess the implication of the NADPH oxidase pathway. Therefore, 3 types of treatment were given to wild-type (WT) and eNOS-/- mice: group 1 received ramipril for 5 weeks and a co-treatment with ramirpil plus nitroglycerine (NTG) during the last 4 days, group 2 received only NTG, and group 3 served as control. Relaxations to NTG (0.1 nmol/L to 0.1 mmol/L) were determined on U44619, a thromboxane analogue, precontracted rings, and O2-* production were assessed on aorta homogenates with the lucigenin-enhanced chemiluminescence technique. Cyclic guanosine monophosphate and reverse-transcriptase-polymerase chain reaction analyses were performed on whole mouse aortas. In WT group 2, the concentration-effect curves to NTG were significantly shifted to the right: the pD2 was 6.16 +/- 0.17 (n = 6) vs 6.81 +/- 0.10 (n = 6) in WT group 3 (not exposed to NTG; P < 0.05) and O2-* production was enhanced from 100% +/- 11% (n = 9) to 191% +/- 21% (n = 6; P < 0.01). In contrast, in WT group 1, the rightward shift was abolished: the pD2 value was 6.73 +/- 0.13 (n = 6; NS vs group 3 WT) and O2-* production was 117% +/- 6% (n = 7; NS vs group 3 WT). In eNOS groups 1 and 3, similar data were observed: the pD2 values were 7.58 +/- 0.08 and 7.38 +/- 0.11 (NS) vs 6.89 +/- 0.20 in eNOS group 2 (n = 6; P < 0.01). In the WT mice aortas, ramipril treatment significantly increased the cyclic guanosine monophosphate levels (reflecting nitric oxide availability), which returned to control values after in vivo co-treatment with a bradykinin BK2 antagonist (Icatibant). In both strains, candesartan, an AT1 blocker, was also able to protect against the development of nitrate tolerance. Moreover, before NTG exposure, ramipril treatment decreased p22phox and gp91phox (essential NADPH oxidase subunits) mRNA expression in aortas from both mice strains. In conclusion, long-term ramipril treatment in mice protects against the development of nitrate tolerance by counteracting NTG-induced increase in O2 production, which involves a direct interaction with the NADPH oxidase pathway and seems to be completely independent of the eNOS pathway.
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PMID:Ramipril treatment protects against nitrate-induced oxidative stress in eNOS-/- mice: An implication of the NADPH oxidase pathway. 1689 13

This study was aimed at investigating the effects of Angiotensin (Ang) II stimulation on T lymphocytes mRNA expression of angiotensinogen (AGTN), angiotensin-converting enzyme (ACE) and AT1-receptor (R) and on ACE activity and Ang II content. The effects of Ang II stimulus were studied in lipopolysaccharide (LPS)-stimulated or not stimulated lymphocytes. mRNA expression for interferon-gamma (INF-gamma) was also studied to investigate whether a link between lymphocyte RAS and immunological function might occur. mRNAs for AGTN, ACE and AT1-R were obtained from peripheral blood of 18 healthy subjects and were quantified by real time quantitative transcriptase-polymerase chain reaction (PCR). ACE activity was assayed in cell pellets and supernatants by measuring the hippuric acid formation by high performance liquid chromatography (HPLC) and Ang II cell content was measured by radioimmunoassay (RIA) after HPLC separation. All determination were performed under baseline conditions and after the addition of 10(e- 13) M Ang II to LPS-stimulated or unstimulated lymphocytes. Ang II caused a significant upregulation of T subset lymphocytes gene expression of ACE and AT1-R and of INF gamma, and a marked increase in ACE activity and cell Ang II concentration. AGTN gene was never expressed. All these effects were further enhanced in T lymphocytes presitmulated by LPS and completely inhibited by Irbesartan. Our findings strongly support the evidence of a positive Ang II driven autocrine loop that upregulates cell RAS of isolated lymphocytes and activates the immuno response. The immuno-potentiating effect of Ang II, specifically shown in T subset, can be deleterious when local RAS are disregulated as in cardiovascular atherosclerotic disease.
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PMID:Angiotensin II upregulates renin-angiotensin system in human isolated T lymphocytes. 1872 52

Experiments were performed to elucidate the mechanism of action of a 7-day oral administration of the sulfur-containing angiotensin-converting enzyme (ACE) inhibitor 3-thienylalanine-ornithyl-proline (TOP; 10 mg/kg/d) on endothelial dysfunction and oxidative stress compared with that of captopril (control; 40 mg/kg/d) in spontaneously hypertensive rats. The differential expression of messenger RNA by real-time reverse-transcriptase-polymerase chain reaction and protein by Western blot analysis was assessed for the markers nicotinamide adenine dinucleotide phosphate oxidase, p22phox, endothelial nitric oxide (NO) synthase, and AT1 receptor. Furthermore, TOP-induced vascular relaxation was also investigated using rat aortic rings in an organ bath. TOP significantly downregulated both messenger RNA and protein expressions of p22phox and AT1 receptor; the latter facilitates vasoconstriction through angiotensin II. In addition, TOP upregulated endothelial NO synthase, thus enhancing the production of NO. Vascular studies revealed that TOP caused endothelium-dependent vasorelaxation. In conclusion, unlike the free sulfur in captopril, the thiophene ring in TOP may act as a better scavenger of free radicals. Therefore, TOP exerted more significant antihypertensive effects than captopril, not only through angiotensin-converting enzyme inhibition but also through more effective antioxidation, because the inherent thiophene moiety resulted in the enhanced production of NO.
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PMID:Sulfur-containing angiotensin-converting enzyme inhibitor 3-thienylalanine-ornithyl-proline activates endothelial function and expression of genes involved in Renin-Angiotensin system. 2323 42

The leaf blight caused by the genus Alternaria is one of the most epidemic diseases on watermelon, and A. tenuissima is the dominant pathogenic species in China. Mycoviruses are found ubiquitously in filamentous fungi, and an increasing number of novel mycoviruses infecting the genus Alternaria have been reported. In this study, a mycovirus from A. tenuissima strain SD-BZF-12 was identified and characterized, whose genome size was very similar with Alternaria alternata chrysovirus 1-N18 (AaCV1-N18). The dsRNA1- and dsRNA2-encoded proteins of the virus had 99 % identities with counterparts of AaCV1-N18; and the dsRNA3- and dsRNA4-encoded proteins of the virus showed the 80 % and 94 % sequence identities with proteins deduced from dsRNA4 and dsRNA3 of AaCV1-N18, respectively. Intriguingly, dsRNA5 of the virus encoded a truncated protein with 68 amino acids (aa) by comparing with 115 aa of AaCV1-N18 dsRNA5. Phylogenetic analysis of RNA-dependent RNA polymerase domain suggested that the virus clustered together with AaCV1-N18. Based on these characteristics, the mycovirus was identified to be a novel strain of AaCV1 and designated as AaCV1-AT1. In addition, no obvious differences were observed on colony morphology between AaCV1-AT1-infected and virus-cured strains of A. tenuissima; however, AaCV1-AT1 infection reduced colony growth rate and spore production ability on host fungus, and increased the median effective concentration of difenoconazole or tebuconazole on its host. This is the first report of AaCV1-AT1 associated with A. tenuissima.
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PMID:Molecular and biological characterization of a novel strain of Alternaria alternata chrysovirus 1 identified from the pathogen Alternaria tenuissima causing watermelon leaf blight. 3210 62


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