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

---

Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effector hormone of the renin-angiotensin system, angiotensin II, plays a major role in cardiovascular regulation. In rats, both angiotensin receptor subtypes, AT(1) and AT(2), are up-regulated after myocardial infarction but previous studies failed to identify the cell types which express the AT(2) receptor in the heart. To address this question we established a single-cell reverse transcriptase-polymerase chain reaction for AT(1) and AT(2) receptors to determine whether these receptor subtypes are expressed in adult rat cardiomyocytes before and 1 day after myocardial infarction. By laser-assisted cell picking, section profiles of single cells without genomic DNA contamination were isolated. After dividing samples into two identical aliquots, polymerase chain reaction amplification for AT(1) and AT(2) receptors was carried out and polymerase chain reaction products were subjected to gel electrophoresis. Compared to control (n = 4) and sham-operated animals (n = 4), the number of cardiomyocytes expressing the AT(1) receptor mRNA 1 day after myocardial infarction (n = 4) was not changed (42% and 33% versus 45%, respectively). On the other hand, AT(2) receptor mRNA was expressed in 8% and 13%, respectively, of cardiomyocytes gained from control (n = 4) and sham-operated animals (n = 4) and in 14% isolated after myocardial infarction (n = 4). These results demonstrate for the first time that the AT(2) receptor is expressed in adult cardiomyocytes in vivo. They further suggest that the previously observed up-regulation of cardiac AT(1) and AT(2) receptors after myocardial infarction involves cell types other than cardiomyocytes.
...
PMID:Expression of angiotensin AT(1) and AT(2) receptors in adult rat cardiomyocytes after myocardial infarction. A single-cell reverse transcriptase-polymerase chain reaction study. 1093 63

Soluble guanylyl cyclase activity and its stimulation by diethylamineNONOate was measured in aortae from hypertensive TGR(mREN2)27 rats (TGR) and Sprague-Dawley controls. Superoxide dismutase was added in vitro to evaluate the contribution of oxidative breakdown of nitric oxide (NO) by superoxide anions. Expression of soluble guanylyl cyclase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Basal and stimulated soluble guanylyl cyclase activity was significantly reduced in TGR rats, addition of superoxide dismutase had no effect. Expression of soluble guanylyl cyclase subunits was not different between strains. The independent contribution of hypertension and the overactive renin-angiotensin system to soluble guanylyl cyclase subsensitivity was assessed after normalization of TGR's blood pressure by the Ca(2+)-channel blocker amlodipine or the angiotensin converting enzyme-inhibitor enalapril. Soluble guanylyl cyclase activity in TGR was slightly increased by amlodipine and almost completely restored by enalapril. In conclusion, TGR showed desensitized vascular soluble guanylyl cyclase, depending on their overactive renin-angiotensin system.
...
PMID:Contribution of the renin-angiotensin system to subsensitivity of soluble guanylyl cyclase in TGR(mREN2)27 rats. 1096 40

Recently, the genes of components of the renin-angiotensin system (RAS), namely angiotensinogen (AGT), angiotensin converting enzyme and angiotensin II receptor have been described in adipose tissue. In animal models the angiotensinogen in adipose tissue has been implicated in the pathogenesis of metabolic alterations and hypertension associated with obesity. The aim of our study was to evaluate the AGT gene expression both in visceral and subcutaneous adipose tissue in obese patients and lean subjects. AGT mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR) using specific primers. AGT mRNA was expressed at variable levels in obese patients. It was significantly greater in visceral than in subcutaneous adipose tissue. Positive and significant correlation was found between the expression of AGT in visceral adipose tissue and BMI. These data suggest that angiotensinogen may be determinant of fat distribution and may be involved in the plurimetabolic syndrome of central obesity.
...
PMID:Gene expression of angiotensinogen in adipose tissue of obese patients. 1099 36

Renin secretion can be stimulated by ATP via purinergic P2Y receptors. ATP is a cotransmitter with norepinephrine and is released from the cytosol during cell damage. Such release could account for the de novo renin expression seen in the proximal tubule in renal disease and in myocardial infarct borders. Whereas most P2Y purinoceptor subtypes utilize phosphoinositide signal-transduction pathways, the effector mechanisms of the subtype P2Y(11) also involve increases in cAMP, a well-known renin secretagogue and stimulus to renin production. The present study tested the effect of ATP on human renin gene (REN) promoter activity and the role of P2Y(11). By means of reverse transcriptase-polymerase chain reaction, we found that renin-expressing Calu-6 cells express P2Y(11) mRNA. Expression was also detected in the brain, kidney, testis, muscle, liver, and spleen. We made a novel cell line (Calu-6/P2Y11) in which P2Y(11) cDNA, under the control of a strong promoter, was stably integrated into genomic DNA. These cells produced P2Y(11) mRNA during culture. Treatment of Calu-6/P2Y11 cells with 1 mmol/L ATP caused a 3-fold increase in renin mRNA and protein over 36 hours. Transient transfection of Calu-6/P2Y11 cells with constructs containing 896 bp of human REN 5'-flanking DNA linked to the luciferase reporter gene led to a 5.8+/-0.6-fold increase (mean+/-SEM) in reporter activity in response to ATP (P=0.0015). In contrast, UTP produced only a 1.4+/-0.1-fold increase (P=0.016). For ADP, it was 1.7+/-0.1-fold (P=0.011). The response profile was ATP>ADP>AMP=adenosine=0, consistent with a P2Y(11) effect. Mutation of the cAMP response element (CRE) located at -222 in the REN promoter DNA abolished the effect of ATP. Furthermore, ATP induced a rapid, time-dependent increase in the phosphorylation of CRE binding protein (CREB) and activating transcription factor-1. These data implicate a cAMP pathway in mediation of the P2Y(11) effect. In conclusion, we have made a novel cell line that overexpresses the P2Y(11) purinoceptor. Stimulation of these cells by ATP activates a cAMP signal-transduction pathway that phosphorylates CREB and stimulates renin promoter activity via the CRE at -222. The data raise the possibility of a contribution of ATP/P2Y(11) effects to sympathetic stimulation of renin, as well as to responses in renin seen after tissue damage, such as in kidney disease and myocardial infarction.
...
PMID:Capacity for purinergic control of renin promoter via P2Y(11) receptor and cAMP pathways. 1111 31

Ventricular pacing leads to a dilated myopathy in which cell death and myocyte hypertrophy predominate. Because angiotensin II (Ang II) stimulates myocyte growth and triggers apoptosis, we tested whether canine myocytes express the components of the renin-angiotensin system (RAS) and whether the local RAS is upregulated with heart failure. p53 modulates transcription of angiotensinogen (Aogen) and AT(1) receptors in myocytes, raising the possibility that enhanced p53 function in the decompensated heart potentiates Ang II synthesis and Ang II-mediated responses. Therefore, the presence of mRNA transcripts for Aogen, renin, angiotensin-converting enzyme, chymase, and AT(1) and AT(2) receptors was evaluated by reverse transcriptase-polymerase chain reaction in myocytes. Changes in the protein expression of these genes were then determined by Western blot in myocytes from control dogs and dogs affected by congestive heart failure. p53 binding to the promoter of Aogen and AT(1) receptor was also determined. Ang II in myocytes was measured by ELISA and by immunocytochemistry and confocal microscopy. Myocytes expressed mRNAs for all the constituents of RAS, and heart failure was characterized by increased p53 DNA binding to Aogen and AT(1). Additionally, protein levels of Aogen, renin, cathepsin D, angiotensin-converting enzyme, and AT(1) were markedly increased in paced myocytes. Conversely, chymase and AT(2) proteins were not altered. Ang II quantity and labeling of myocytes increased significantly with cardiac decompensation. In conclusion, dog myocytes synthesize Ang II, and activation of p53 function with ventricular pacing upregulates the myocyte RAS and the generation and secretion of Ang II. Ang II may promote myocyte growth and death, contributing to the development of heart failure.
...
PMID:Canine ventricular myocytes possess a renin-angiotensin system that is upregulated with heart failure. 1117 97

We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SBP in SHR. Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment. But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner.
...
PMID:Chronic treatment with amlodipine modulates adrenocortical angiotensin II receptors in spontaneously hypertensive rats. 1141 1

These studies investigated the question of whether the intrarenal renin-angiotensin system (RAS) is essential for transforming growth factor-beta1 (TGF-beta1) gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose in vitro. Antisense and sense angiotensinogen (ANG) cDNAs were stably transfected into rat immortalized renal proximal tubular cells (IRPTC). ANG secretion from rat IRPTC was quantified by a specific RIA for rat ANG. Cellular ANG, TGF-beta1, and collagen alpha1 (type IV) mRNA levels were determined by Northern blot analysis or by reverse transcriptase-PCR assay. Hypertrophy of IRPTC was analyzed by Western blotting of cellular p27(Kip1) protein, flow cytometry, and cellular protein assay. The results showed that stable transfer of antisense ANG cDNA into IRPTC suppressed the basal TGF-beta1 and collagen alpha1 (type IV) mRNA expression and blocked the stimulatory effect of high glucose (i.e., 25 mM) on TGF-beta1 and collagen alpha1 (type IV) mRNA expression and induction of IRPTC hypertrophy. In contrast, stable transfer of sense ANG cDNA into IRPTC had no significant effect on these parameters. These data demonstrate that local intrarenal RAS activation is essential for TGF-beta1 gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose.
...
PMID:Essential role(s) of the intrarenal renin-angiotensin system in transforming growth factor-beta1 gene expression and induction of hypertrophy of rat kidney proximal tubular cells in high glucose. 1180 57

To evaluate the expression of the renin-angiotensin system (RAS) genes in visceral (VAT) and subcutaneous adipose tissue (SAT) in normotensive subjects with different body mass index (BMI). Adipose tissue was obtained from 22 normotensive (12 normal weight and 10 overweight) patients during surgery for colecystectomy. Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein levels were measured by reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. The AGT mRNA and AT1 receptor mRNA levels were significantly higher in VAT than in SAT; AGT mRNA levels were higher, although not significantly, in overweight subjects in both SAT and VAT. There was no significant difference in ACE gene expression in the two tissues, and no expression of angiotensin II receptor type 2 (AT2). Finally, we failed to find mRNA for the renin gene in adipose tissue. The presence of AGT and ATI receptor in SAT and VAT was confirmed by Western blot analysis. Our study demonstrates the presence--and different levels of expression--of the various components of the RAS system (AGT, ATI, and ACE) in human SAT and VAT, and highlights the different role and regulation of the system in the two tissues. Its high expression in VAT suggests that its regulation and function are involved in all conditions where visceral adiposity is present.
...
PMID:Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. 1202 38

The physiological effects of angiotensin II (Ang II) are mediated through specific AT(1) and AT(2) receptors. Tissue distribution and affinity of these receptors have been explored in binding studies, reverse transcriptase-polymerase chain reaction and in situ hybridisation. Sequencing has also demonstrated gene polymorphisms for both AT(1) and AT(2) receptors. Numerous potent nonpeptide antagonists of angiotensin converting enzyme or of AT receptors have been developed, thus providing a precise analysis of the physiology of the renin-angiotensin system. AT(1) receptors are widely expressed throughout adult tissues, while AT(2) receptors are mainly expressed in the fetus. Receptor density on the cell surface is regulated by multiple hormonal, cytokine and metabolic factors, and is thus profoundly affected by various pathological conditions, especially in the myocardium, kidney and blood vessels. To date, the precise molecular basis for these modifications has not been fully explained, although it may rely in part upon AT receptor gene polymorphisms, which could thus constitute increased risk factors for cardiovascular disease. AT(1) and AT(2) receptor expression is therefore influenced by both age and environmental specifications and is likely to be increased by a diet rich in salt or cholesterol, thus justifying the use of Ang II receptor antagonists in morbidity-mortality studies in high-risk patients.
...
PMID:[Exploring AT(1) and AT(2) angiotensin II receptors in humans]. 1203 85

There is evidence that fetal growth restriction is associated with impaired nephrogenesis and reduced numbers of mature nephrons at birth. It has been proposed that such impairment of renal growth may contribute to increased blood pressure in later life. Although prostaglandins (PG) play a key role in kidney development, it is unknown whether a poor fetal substrate supply alters the synthesis or actions of PG within the fetal kidney. Using real-time reverse transcriptase PCR, we have measured the effect of chronic placental restriction (PR) on the renal expression of PG endoperoxide G/H synthase-2 (PGHS-2), PGE(2) receptors EP(2) and EP(4), and renin mRNA in the sheep fetus in late gestation. Restriction of placental growth reduced fetal body weight (PR: 3.2 +/- 0.2 kg, control: 4.8 +/- 0.2 kg) and total kidney weight (PR: 19.7 +/- 1.8 g, control: 25.1 +/- 1.3 g). Mean fetal arterial PO(2) was reduced by PR (PR: 15.03 +/- 0.67 mm Hg, control: 21.3 +/- 0.87 mm Hg). Renal PGHS-2 mRNA was increased in the PR group (PR: 2.26 +/- 0.38, control: 1.20 +/- 0.31) and was inversely related to mean fetal arterial PO(2) in the PR and control groups [PGHS-2: -0.17 (PO(2)) + 4.69, r(2) = 0.26]. PR also increased renal EP(2) (PR: 1.57 + 0.24, control: 0.82 + 0.13) but not EP(4) mRNA. Renin mRNA was directly related to renal EP(2) [renin = 0.37 (EP(2)) + 0.97, r(2) = 0.29] and EP(4), [renin = 0.75 (EP(4)) + 0.44, r(2) = 0.38] mRNA expression. Thus, the restriction of placental growth and associated chronic hypoxemia appear to increase the renal capacity to synthesize and respond to PG, which may play an important role in maintaining renin mRNA expression in the growth-restricted fetus.
...
PMID:Placental restriction increases the expression of prostaglandin endoperoxide G/H synthase-2 and EP2 mRNA in the fetal sheep kidney during late gestation. 1243 65


<< Previous 1 2 3 4 5 6 7 Next >>

---