Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. 214 33

Cloned cDNA sequences for human preangiotensinogen have been isolated from a human liver cDNA library by hybridization with a restriction fragment derived from a previously cloned cDNA for rat preangiotensinogen. Analyses by nucleotide sequence determination, S1 nuclease mapping, and RNA blot hybridization indicate that human preangiotensinogen is encoded by two mRNAs that differ only in the length of the 3'-untranslated region. The deduced amino acid sequence shows that the mature angiotensinogen consists of 452 amino acid residues with the angiotensin sequence at its amino-terminal portion. Two potential initiation sites have been discussed. These are the methionine codon located at the position exactly corresponding to the initiation site of rat preangiotensinogen mRNA and an additional methionine codon positioned nearest the 5' end of the mRNA. The amino acid sequences starting at either of the initiation sites and preceding the angiotensin sequence constitute a large number of hydrophobic amino acid residues, thus representing the signal peptide characteristic of the secretory proteins. Human and rat preangiotensinogens show that 63.6% of the amino acid positions of the two proteins are identical. However, the amino-terminal portions directly distal to angiotensin I diverge markedly between the two proteins and differ in their possible glycosylation sites. These structural differences may contribute to the known species specificity exhibited by renin.
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PMID:Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. 608 75

Recent studies have documented the presence of a complete renin-angiotensin system in the proximal tubule of the kidney: however, little is known about the regulation of renin in this proximal tubular system. Therefore, we performed the present studies to learn whether the behavior of the renin system in cultured proximal tubule is similar to that of the juxtaglomerular renin system. Basal renin secretion from rabbit proximal tubular cells in primary culture was low and not affected by isoproterenol (10(-5) mol/L), diltiazem (10(-5) mol/L), or a zero-calcium bath (O nmol/L). Only the calcium ionophore A23187 (10(-4) mol/L) significantly reduced renin secretion in these cells (from 2.44 +/- 0.37 to 1.14 +/- O.08 ng angiotensin I/mg protein per hour, P<.05). When the proximal tubular cells were lysed so the effects of the test agents on intracellular renin content could be assessed, isoproterenol caused a significant twofold (107 percent) increase (from 2.02 +/- 0.56 to 4.18 +/- 0.81 ng angiotensin I/mg protein per hour, P<.05), whereas diltiazem, A23187, and zero- and high-calcium baths did not produce a significant change. The effects of these agents on renin mRNA were examined in rabbit and rat proximal tubular cells in primary culture with the use of an S1 nuclease protection assay. Densitometry analysis of renin mRNA and either GAPDH mRNA (rat) or alpha-actin (rabbit) showed no significant alterations in renin mRNA abundance. In summary, these results confirm the presence of renin mRNA in cultured proximal tubular cells and suggest that a low-level, constitutive secretion of renin occurs in this system that is decreased by A23187. Moreover, the results also suggest that proximal tubular renin is regulated, albeit differently from the juxtaglomerular renin system. Finally, short-term increments in proximal tubular renin occur without a change in renin mRNA.
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PMID:Renin regulation in cultured proximal tubular cells. 864 45

The cis elements mediating activation of the tyrosine hydroxylase gene by angiotensin II were examined by transfecting tyrosine hydroxylase promoter-luciferase constructs into cultured bone adrenal medullary cells. Angiotensin II-responsive elements are located within -54/+25-bp and -269/-55-bp promoter regions and were identified, respectively, as cyclic AMP (CRE)- and 12-O-tetradecanoylphorbol 13-acetate responsive element (TRE)-like sequences. Unlike CRE, TRE also supports basal promoter activity. Mutations of TRE or CRE that reduced angiotensin II stimulation abolished in vitro binding of nuclear proteins to those elements, suggesting that proteins forming CRE- and TRE-inducible complexes may mediate angiotensin II stimulation. The TRE is adjacent to a dyad symmetry element. Those two sites form a common regulatory unit in which the dyad symmetry element acts as a repressor of the TRE site. Isolated dyad symmetry element did not bind nuclear proteins in vitro. In supercoiled DNA it exhibited S1 nuclease sensitivity and was recognized by a DNA cruciform-specific antibody consistent with the extrusion of a cruciform structure that overlaps with the TRE. A mutation that abolished formation of the cruciform correlated with a loss of repressor activity. We propose a novel model of tyrosine hydroxylase gene regulation in which functions of the TRE are modulated via structural transition in the adjacent DNA.
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PMID:The roles of CRE, TRE, and TRE-adjacent S1 nuclease sensitive element in the regulation of tyrosine hydroxylase gene promoter activity by angiotensin II. 866 99