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

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overlapping genomic clones containing the entire sequence of the human angiotensin I-converting enzyme (ACE) gene were isolated from a lamda phage human DNA library. This gene spans 21 kilobases (kb) and comprises 26 exons, ranging in size from 88 to 481 base pairs. Intron-exon boundaries were sequenced and the relative positions of the exons were mapped. The two different mRNAs transcribed from the ACE gene were assigned to their respective exons. The large endothelial type ACE mRNA (4.3 kb long) is transcribed from exon 1 to exon 26, excluding exon 13. The 3-kb long testicular ACE mRNA is transcribed from exon 13 to exon 26. Exon 13 encodes for the 67 amino acids of the NH2-terminal region of the testicular ACE, whereas downstream exons encode a sequence common to both isozymes. The gene duplication suggested by the internal homology of the endothelial ACE mRNA is now confirmed by the presence of two homologous clusters of eight exons (exons 4-11 and exons 17-24) having similar sizes and codon phases at exon-intron boundaries. The presence of two alternate promoters was investigated by ribonuclease protection assays. The different 5' ends of the two ACE transcripts revealed a promoter for the endothelial ACE mRNA in the 5'-flanking region of the first exon and a promoter for the testicular ACE mRNA situated in intron 12.
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PMID:Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene. 165 27

Angiotensin-converting enzyme (ACE) is a zinc-containing dipeptidyl carboxypeptidase that catalyzes the conversion of angiotensin I to the potent vasoconstrictor angiotensin II. By analyzing cDNA and genomic DNA, we have constructed a consensus sequence encoding the testis isozyme of mouse ACE. Testis ACE cDNA contains 2,435 base pairs and encodes a protein of 732 amino acids. The N-terminal 66 amino acids are unique to the testis isozyme, while the remaining 666 are identical to the carboxyl half of mouse somatic ACE. The overall conservation of amino acid sequence between the testis isozymes of the mouse, rabbit, and human is 78 to 84%. The conservation of amino acids for the N-terminal domain uniquely expressed within the testis is 63 to 67% between these species. Primer extension and RNase protection experiments show that RNA transcription of the testis ACE isozyme begins 16 or 17 bases upstream from the translation start site. A sequence element resembling a TATA box is found 25 bases 5' of the transcription start site. To create its unique isozyme of ACE, the testis begins mRNA transcription in the middle of the exonic-intronic structure of somatic ACE, within a sequence treated as an intron by somatic tissues. Testis ACE is not the result of alternative RNA splicing but seems due to the start of transcription at a unique site within the ACE gene.
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PMID:Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene. 216 36

Serum levels of various hydrolytic enzymes in prostatic cancer patients with or without bone metastasis were compared with those in patients with prostatic hypertrophy and in the control subjects. The enzymes tested included 11 aminopeptidases, 2 endopeptidases, dipeptidyl carboxypeptidase, esterase, acetyl cholinesterase, and RNase. Although most of the enzymatic levels tended to be decreased in the cancer patients without bone metastasis, they tended to be increased in those with metastasis as well as in the patients with prostatic hypertrophy. Thus, bone metastasis is an important factor affecting the serum levels of hydrolytic enzymes in cancer patients. Of the enzymes tested, RNase was unique in that its serum levels were significantly increased regardless of the existence of bone metastasis. This enzyme may become a marker of malignancy.
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PMID:Different tendencies of changes in hydrolytic enzyme activities in sera from prostatic cancer patients with or without bone metastasis. 608 28

The effects of different steroids on the expression of angiotensin AT1 receptors by the human hepatoma cell line, PLC-PRF-5 was studied. Dexamethasone and aldosterone decreased the specific binding of [3H]angiotensin II to intact PLC-PRF-5 cells by 57 +/- 4% and 54 +/- 2%, respectively, compared to control, untreated cells. EC50 values for dexamethasone, cortisol and aldosterone were 1.8 +/- 0.6, 40 +/- 6, and 310 +/- 20 nM, respectively, suggesting that these effects were mediated via a glucocorticoid receptor. Scatchard analysis revealed that dexamethasone decreased the number of angiotensin AT1 receptors expressed (50 +/- 4% relative to control) with no change in receptor affinity. Treating cells with dexamethasone in the presence of either an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist did not prevent the reduction in angiotensin AT1 receptor expression, ruling out a mechanism involving a dexamethasone induced increase in endogenous angiotensin II production. A ribonuclease protection assay established that the steady state level of angiotensin AT1 receptor mRNA in dexamethasone treated cells was reduced to 34.7 +/- 8.4% of untreated cells. The decrease in the number of angiotensin AT1 receptors expressed on the cell surface after treatment with dexamethasone therefore seems likely to reflect the decreased steady state level of the mRNA coding for this receptor.
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PMID:Glucocorticoids regulate the expression of angiotensin AT1 receptors, in the human hepatoma cell line, PLC-PRF-5. 777 81

We have recently found that vascular natriuretic peptide (NP)-A receptor mRNA is upregulated in genetically hypertensive (SHR-SP/Izm) and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In the present study, we examined the effects of antihypertensive treatments on aortic NP-A receptor mRNA expression in these hypertensive rats using ribonuclease protection assay. Oral administration of an angiotensin converting enzyme inhibitor, derapril, but not a calcium channel blocker, manidipine, produced a significant decrease of the NP-A receptor mRNA level after 4 weeks, while both antihypertensive agents showed similar hypotensive effects. Plasma renin was high in SHR-SP/Izm and low in DOCA-salt rats. These results suggest that the vascular renin-angiotensin system rather than the blood pressure has an important role in the regulation of the vascular NP-A receptor.
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PMID:Angiotensin converting enzyme inhibitor but not calcium blocker down-regulates gene expression of vascular natriuretic peptide receptor in hypertensive rats. 781 Dec 41

To examine the regulation of angiotensin receptors in vascular smooth muscle cells, we studied the effects of antihypertensive drugs on angiotensin type 1A (AT1A) receptor gene expression in aortic smooth muscle cells (ASMCs) from spontaneously hypertensive rats (SHRs) using both ribonuclease protection assay and reverse-transcription polymerase chain reaction. An increase in AT1A receptor gene expression in ASMCs of SHRs was induced by treatment with an angiotensin converting enzyme inhibitor (enalapril) for 2 weeks and 4 weeks, but not by other types of antihypertensive drugs such as alpha-blocker (doxazosin), alpha, beta-blocker (arotinolol), Ca antagonist (nicardipine) or vascular smooth muscle relaxant (hydralazine). Since all antihypertensive drugs lowered the blood pressure of the rats almost equally, our results suggest that AT1A receptor gene expression in ASMCs of SHRs may be regulated by the vascular renin-angiotensin system.
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PMID:Angiotensin-converting enzyme inhibitor increases angiotensin type 1A receptor gene expression in aortic smooth muscle cells of spontaneously hypertensive rats. 815 34

We previously demonstrated that angiotensin converting enzyme (ACE) inhibitor normalizes the up-regulated gene expression of vascular natriuretic peptide type A (NP-A) receptor in hypertensive rats. To elucidate the mechanism, we examined the effect of angiotensin II receptor (AT1) antagonist (TCV-116) and bradykinin receptor (B2) antagonist (Hoe 140) on the NP-A receptor mRNA level in the aorta of genetically hypertensive rats (SHR-SP/Izm) using ribonuclease protection assay. The effect of ACE inhibitor on the NP-A receptor mRNA level was completely abolished by a concomitant administration of Hoe 140, while TCV-116 did not show any significant effect on the NP-A receptor mRNA level. These results suggest that bradykinin plays an important role in the regulation of the vascular NP-A receptor gene expression.
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PMID:Angiotensin converting enzyme inhibitor normalizes vascular natriuretic peptide type A receptor gene expression via bradykinin-dependent mechanism in hypertensive rats. 857 74

The renin-angiotensin system (RAS) has been implicated in the development of hypertensive glomerulosclerosis. However, there are no experimental findings clearly demonstrating activation of glomerular RAS in hypertensive nephropathy. Using the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model of hypertensive glomerulosclerosis, we examined the relationship between the sequential changes in urinary albumin excretion (UAE), renal morphology, and glomerular mRNA expression for transforming growth factor-beta (TGF-beta) and fibronectin (FN) and glomerular mRNA levels for RAS components, and determined the effects of the angiotensin II (Ang II) type 1 (AT-1) receptor antagonist (candesartan) and equihypotensive hydralazine on these parameters. In SHRSP, UAE was normal at nine weeks of age and increased by 12 weeks. Plasma renin activity, plasma Ang II concentration, and angiotensin converting enzyme (ACE) activity were not higher in 9- and 12-week-old SHRSP than in WKY. RNase protection assay revealed higher glomerular mRNA levels for angiotensinogen, ACE, and AT-1a and AT-1b receptors in 9-, 12-, and 14-week-old SHRSP than in WKY. The glomerular mRNA levels for TGF-beta and FN in SHRSP were increased from nine weeks of age. SHRSP had a greater glomerulosclerosis index (GSI) at 24 weeks of age than did WKY. Administration of candesartan for two weeks, but not of hydralazine, markedly reduced UAE and normalized mRNA levels for TGF-beta, FN, and RAS components. Candesartan administration for 12 weeks virtually prevented the progression of glomerulosclerosis in rats. We conclude that in SHRSP, RAS activation and increased sensitivity to Ang II in glomeruli play important roles in the progression of glomerulosclerosis.
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PMID:Candesartan prevents the progression of glomerulosclerosis in genetic hypertensive rats. 940 67

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 +/- 18% increase above basal levels, 185 +/- 18 versus 128 +/- 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II. Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY. These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.
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PMID:Increased mRNA expression of cardiac renin-angiotensin system and collagen synthesis in spontaneously hypertensive rats. 954 81

Plasma angiotensin I-converting enzyme (ACE) levels are different between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKYHD) rat. This interstrain variability in plasma ACE levels is independent of blood pressure and is genetically linked to the ACE gene. The present study explored the hypothesis of an interstrain variability of tissue ACE activity and ACE gene expression levels. Tissue ACE levels were studied by enzymic activity measurement in the membrane fraction, and ACE mRNA levels were quantified by solution hybridization-ribonuclease protection assay. In lung, heart, kidney, and duodenum, membrane-bound ACE activity and ACE mRNA amount were significantly higher in WKYHD rats compared with SHRSPHD rats. No difference was observed in the testis where a specific isoform of the enzyme is produced. Our results suggest that in addition to determine differential plasma ACE levels between the WKYHD and SHRSPHD strains, the interstrain genetic variability also determines differential ACE mRNA and membrane-bound enzyme levels in somatic tissues. This likely reflects a difference in the ACE gene expression due to genetically determined regulatory mechanisms operative in all somatic tissues.
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PMID:Interstrain differences in angiotensin I-converting enzyme mRNA and activity levels. Comparison between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. 1036 81


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