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:3.4.23.15 (renin)
35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we try to determine the influence of renal nerve activity on renal function, plasma renin activity (PRA), and the corresponding expression of renin and angiotensinogen genes in the kidney. In pentobarbitone-anesthetized rats, the left renal nerves were stimulated (15 V, 0.2 ms) at frequencies to reduce left renal blood flow by 15, 30, and 45%. There were corresponding reductions in glomerular filtration rate from 12 to 52% and absolute and fractional sodium excretions from 20 to 75%. PRA levels in control rats were 10.8 +/- 1.5 and were increased to 65.9 +/- 9.1, 144.2 +/- 19.7, and 277.2 +/- 22.0 ng angiotensin I.h-1.ml-1 after 1 h at each of the three levels of nerve stimulation. Renal renin mRNA was similar in innervated and denervated kidneys and was not affected by the lowest level of nerve stimulation; however, neurally induced decreases in blood flow to 30 and 45% increased renin mRNA levels by 3.0- and 3.4-fold (both P < 0.05), respectively. Angiotensinogen mRNA levels were higher (P < 0.05) in kidneys subjected to the lowest level of nerve stimulation, but when renal blood flow was reduced by 30 and 45%, expression of this gene was unchanged. Stimulation of the renal nerves in the presence of the beta 1-adrenoceptor antagonist atenolol only doubled PRA at the highest rates of stimulation. Neither renal renin nor angiotensinogen mRNA were changed during neurally mediated reductions in renal blood flow of 15 or 30% after administration of atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of renal nerves on expression of renin and angiotensinogen genes in rat kidneys. 814 Dec 81

Angiotensinogen is the substrate for the enzyme renin. In addition to the well-characterized low molecular weight forms of angiotensinogen, a high molecular weight form (HMrA) comprises about 15 per cent of the total angiotensinogen in plasma of pregnant women. In the current study the different forms of angiotensinogen were quantitated in different regions of the placenta. The highest concentration of total angiotensinogen was found in the chorion laeve followed by the amnion. It was found that HMrA was the major form of angiotensinogen in all regions of the placenta, accounting for 72, 67, 63, and 59 per cent of the total angiotensinogen in the chorion laeve, chorion plate, amnion, and chorion frondosum, respectively. There was a significant correlation between the distribution of total renin and HMrA. This data in conjugation with previous data indicate that HMrA should be considered a significant component of the renin angiotensin system in the human pregnant state. It is suggested that HMrA may be a component of a tissue specific renin angiotensin system that occurs in the placenta.
...
PMID:Regional distribution of the angiotensinogens in human placentae. 815 90

Activation of antinatriuretic systems such as the renin-angiotensin system, is of major importance in the pathogenesis of sodium retention in cirrhosis. In this study, we studied the intrarenal renin-angiotensin system by measuring renin and angiotensinogen mRNA expression in the kidney of rats subjected to long-term bile duct ligation in a phase before the development of ascites, when sodium retention is already present. Experiments were performed in sham-operated and bile duct-ligated rats 3 wk after surgery. Balance studies showed lower sodium excretion and greater sodium retention in the bile duct-ligated rats compared with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Angiotensin I/ml/hr in the bile duct-ligated group vs. 4.20 +/- 0.74 in the controls) and plasma renin concentration were not different between the two groups. However, plasma renin substrate was significantly decreased in bile duct-ligated animals. Total kidney renin mRNA was significantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densitometric units vs. 0.44 +/- 0.04 in the controls), as determined on Northern-blot analysis and densitometric quantitation. Angiotensinogen mRNA expression in the kidneys of bile duct-ligated rats was significantly decreased (0.09 +/- 0.01 densitometric units) compared with that of the controls (0.21 +/- 0.03). These results indicate that sodium-retaining, nonascitic bile duct-ligated rats show abnormalities of the intrarenal renin angiotensin system that precede changes in plasma renin activity. Our data suggest that the intrarenal renin angiotensin system may participate in the initiation of the renal pathophysiological abnormalities present in bile duct-ligated rats.
...
PMID:Renin and angiotensinogen mRNA expression in the kidneys of rats subjected to long-term bile duct ligation. 818 73

Angiotensinogen is a glycoprotein synthesized mainly in hepatocytes and secreted into the circulation. Angiotensinogen is cleaved by the enzyme renin to produce angiotensin I, which is further converted into a vasoconstricting peptide, angiotensin II, the biologically active peptide of the renin angiotensin system. The concentration of angiotensinogen is rate-limiting in the production of angiotensin I and therefore plays an important role in the regulation of angiotensin II production. The development of recombinant DNA technology has introduced new directions for the study of the angiotensinogen molecule. The human, rat and mouse angiotensinogen gene contains five exons interrupted by four intervening sequences and spans 12 kb approximately. In its 5' flanking region multiple regulating elements, as well as the major control elements, are present. The cloning and sequencing of the angiotensinogen cDNA demonstrates the similarity of angiotensinogen to various serine protease inhibitors produced by the liver and was the beginning of studies looking for new physiological roles of angiotensinogen, in addition to the substrate for renin. The circulating levels of angiotensinogen are altered in many different physiological and pathological states. High levels of this protein are seen in hypercorticism, inflammation, pregnancy, and contraceptive therapy, and low levels are associated with adrenal insufficiency and converting enzyme inhibition. These variations are mostly due to modifications of the hepatic biosynthesis under the control of hormonal factors such as glucocorticoid, estrogen, thyroid hormone, insulin and angiotensin II. In addition, it has been found that these changes in the hepatic biosynthesis are due mainly to changes in the angiotensinogen gene expression.
...
PMID:[Structure and regulation of the expression of the angiotensinogen gene]. 823 38

Cardiovascular renin-angiotensin system plays an important roll in physiological and pathological status. Its autocrine and paracrine functions are to regulate vascular tone, cardiac contractility and to regulate cardiac and vascular growth. It is well known that systemic hypertension induces cardiac hypertrophy, and it can be prevented by antihypertensive drugs. But its mechanism is still unclear. In our study all antihypertensive drugs could prevent left ventricular hypertrophy of genetic hypertension model SHR. Left ventricular Angiotensinogen m-RNA expression of SHR was 2 fold higher than WKY's. All antihypertensive drugs could also prevent left ventricular angiotensinogen m-RNA expression. It is suggested that mechanism of left ventricular hypertrophy which is induced by systemic hypertension is related with cardiac angiotensinogen m-RNA expression. And it can be modulated by any kind of antihypertensive drug treatments.
...
PMID:[Expression and function of cardiovascular local renin-angiotensin system]. 832 Aug 34

The cloning of renin, angiotensinogen and angiotensin converting enzyme genes have established a widespread presence of these components of the renin-angiotensin system in multiple tissues. New sites of gene expression and peptide products in different tissues has provided strong evidence for the production of angiotensin independently of the endocrine blood borne system. In addition, the cloning of the angiotensin receptor (AT1) gene has confirmed the widespread distribution of angiotensin and suggested new functions for the peptide. This review of various tissues shows the variation in gene expression between tissues and angiotensin levels, and the fragmentary state of our knowledge in this area. As yet we cannot state that the gene expression of the substrates, enzymes and peptide products are involved in a single cell synthesis. This is not so much evidence against a paracrine function for tissue angiotensin, as lack of detailed, accurate intracellular information. The low abundance of renin in brain, spleen, lung and thymus compared to kidney, adrenal, heart, testes, and submandibular gland may suggest that there are both tissue renin-angiotensin systems (RAS) and nonrenin-angiotensin systems (NRAS). The NRAS could function through cleavage of angiotensinogen by serine proteinases such as tonin and cathepsin G to form Ang II directly. Although much angiotensinogen is extracellular and could therefore be a site of synthesis outside of the cell, intracellular angiotensinogen in a NRAS process could produce Ang II intracellularly without requiring extracellular conversion of Ang I to Ang II by ACE. In summary, renin mRNA is found in high concentrations in kidney, adrenal and testes and decreasing lower concentrations in ovary, liver, brain, spleen, lung and thymus. Angiotensinogen mRNA is found in the following tissues in descending order of abundance: liver, fat cells, brain (glial cells), kidney, ovary, adrenal gland, heart, lung, large intestine and stomach. It is debatable whether angiotensinogen and renin mRNA are expressed in blood vessels. The evidence that is lacking for a paracrine function of angiotensin is a complete description of the intracellular molecular synthesis and release of Ang II from single cells of promising tissues. Such tissues, SMG, ovary, testes, adrenal, pituitary and brain (neurons and glia) are potent sources of RAS components for future studies. Although the evidence for a paracrine function of angiotensin II is incomplete, it is an important concept for progressing toward the understanding of tissue peptide physiology and the significance of their gene regulation.
...
PMID:Levels of angiotensin and molecular biology of the tissue renin angiotensin systems. 842 6

Recent studies in both experimental animals and man have demonstrated the unique efficacy of converting enzyme inhibitors to prevent or attenuate ventricular remodeling after myocardial infarction. Concomitantly, evidence for a trophic role of the renin-angiotensin system (RAS), as well as for the existence of an intracardiac tissue-resident RAS, has been presented, raising the question whether altered regulation of this cardiac RAS may be associated with the process of ventricular remodeling. We conducted the present study to examine whether cardiac angiotensinogen gene expression is altered after myocardial infarction. Experiments were performed in rats 5 and 25 days after ligation of the left coronary artery or sham operation. Coronary artery ligation resulted in relative infarct sizes averaging 29% and 36% of total left ventricular mass at 5 and 25 days and in marked elevations of left ventricular end-diastolic pressure (LVEDP). Angiotensinogen mRNA levels, measured by solution hybridization assay and confirmed in a second, independent experimental group by RNAse protection assay, were significantly elevated in the non-infarcted portion of the left ventricle at 5 days after infarction when compared to the sham group (22.1 + 3.3 vs. 13.4 +/- 2.0 fg/microgram total RNA; ratio of densitometric absorbance for angiotensinogen/beta-actin: 0.356 +/- 0.041 vs. 0.156 +/- 0.02), and showed a significant correlation with infarct size (r = 0.93). At 25 days, angiotensinogen gene expression had returned to control values. Similarly, no significant differences in angiotensinogen mRNA levels between animals with and without infarction were found in other cardiac tissues (atria, right ventricle). Plasma renin activity was significantly increased over baseline in the infarct group at 5, but not at 25 days. Our results demonstrate that acute hemodynamic embarrassment early after LV infarction is associated with augmented angiotensinogen gene expression. The potential significance of this finding is discussed.
...
PMID:Selective activation of cardiac angiotensinogen gene expression in post-infarction ventricular remodeling in the rat. 847 23

Oral therapy with natural or synthetic estrogens, like ethinylestradiol, suffers from low, suboptimally defined bioavailability and excess hepatic estrogen actions. N,N-alkylated and non-alkylated sulfamates of ethinylestradiol, estradiol and estrone overcome these deficiencies. Ovariectomized Wistar rats (n = 6-7/group) were orally treated for 7 days, and killed on day 8, plasma was gained on days 0, 4, and 8. Systemic estrogenicity was quantified by assessment of uterine weight, vaginal cornification, and measurement of gonadotropins by homologous RIA. Estrogenicity in the liver was analysed. Angiotensinogen was estimated by RIA of angiotensin-1 after incubation of EDTA-plasma with porcine renin. Total and high-density cholesterol were measured by enzymatic methods. Preliminary biotransformation studies were performed after oral administration of 10 micrograms, 5 microCi [2,4,6,7-3H]estradiol sulfamate. Ethinylestradiol led to distinct elevation of angiotensin-1 and dramatic depression of cholesterol fractions, reflecting hepatic estrogen effects, already at doses with marginal systemic effects. Estradiol and estrone had systemic and hepatic estrogenic activity at much higher doses only. Estrogen sulfamates had systemic estrogen activity 10-90-fold above that of their parent estrogen. Non-alkylated sulfamates of given estrogens were more active than N-alkylated ones. Elevation of systemic estrogen activity was always combined with a dramatic reduction of hepatic estrogenicity. Estradiol sulfamate had a 90-fold elevated systemic estrogen activity vs estradiol, but lacked hepatic activity including the 30-fold dose inducing vaginal response. Three hours after administration no unchanged estradiol sulfamate was detectable in plasma. Rather peaks, probably representing estradiol and estrone, were found. Estrogen sulfamates are considered prodrugs of their parent estrogen, which do not interact with any liver function during the first-pass. They represent a new strategy of oral hormone administration. Their main potential seems to be the systemic generation of natural estrogens when used in oral contraceptives.
...
PMID:Sulfamates of various estrogens are prodrugs with increased systemic and reduced hepatic estrogenicity at oral application. 854 Dec 36

Angiotensinogen encodes the only known precursor of angiotensin II, a critical regulator of the cardiovascular system. Transcriptional control of angiotensinogen in hepatocytes is an important regulator of circulating angiotensinogen concentrations. Angiotensinogen transcription is increased by the inflammatory cytokine tumor necrosis factor (TNF)-alpha by a nuclear factor-kappaB-like protein binding to an inducible enhancer called the acute-phase response element. By gel mobility shift assays, we observe two specific acute-phase response element-binding complexes, C1 and C2. The abundance of C2 is not changed by TNF treatment. In contrast, C1 is faintly detected in untreated cells, and its abundance increases by fivefold after stimulation. We identify the nuclear factor-kappaB subunits in these complexes using subunit-specific antibodies in the gel mobility "supershift" assay. The transcriptionally inert nuclear factor-kappaB DNA-binding subunit NF-kappaB1 is present in both control and stimulated hepatocyte nuclei. Its abundance changes weakly upon TNF stimulation. In contrast, the potent transactivating protein Rel A is not found in unstimulated hepatocyte nuclei and is recruited by TNF-alpha into the C1 DNA-binding complex. Overexpression of Rel A results in acute-phase response element transcription. Cotransfection of a chimeric GAL4-Rel A protein with GAL4 DNA-binding sites is a strategy that allows for selective study of Rel A. The GAL4:Rel A chimera is a TNF-alpha-inducible transactivator. Deletion of the amino-terminal 254 amino acids of Rel A produces a constitutive activator (that is no longer TNF-alpha inducible). The cytokine induction of Rel A, then, is mediated through its amino-terminal 254 amino acids. We conclude that Rel A:NF-kappaB1 is a crucial cytokine-inducible transcription factor complex regulating angiotensinogen gene synthesis in hepatocytes and may be involved in controlling the activity of the renin-angiotensin system.
...
PMID:Tumor necrosis factor activates angiotensinogen gene expression by the Rel A transactivator. 861 56

Common molecular variants of the angiotensinogen gene have been associated with human hypertension. The rare Tyr to Cys change at residue 248 of mature angiotensinogen was identified in one pedigree. Heterozygous individuals (Y248C) had a 40% decrease in plasma angiotensinogen concentration and a 35% reduction of the angiotensin I production rate. Recombinant wild-type (Tyr-248) and mutant (Cys-248) proteins were stably expressed in Chinese hamster ovary cells. Angiotensinogen monoclonal antibodies revealed marked differences in the epitope recognition of the mutant protein and allowed the demonstration of its presence in plasma of Y248C individuals. Similar kinetic constants of angiotensin I production with human renin were observed for both proteins. Western blot analysis showed similar heterogeneities; however, a 3-kDa increase in molecular mass for the Cys-248 protein was observed after immunopurification. Metabolic labeling of the intracellular Cys-248 protein showed a 61-kDa band in addition to the 55.5- and 58-kDa bands observed for the Tyr-248 protein, with all bands being sensitive to endoglycosidase H. In addition, pulse-chase studies revealed a slower intracellular processing for the Cys-248 protein. In conclusion, the Cys-248 mutation alters the structure, glycosylation, and secretion of angiotensinogen in Chinese hamster ovary cells and is accompanied by a decrease in plasma angiotensinogen concentration in Y248C individuals.
...
PMID:The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein. 862 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---