Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A collagen network, composed largely of type I and III fibrillar collagens, is found in the extracellular space of the myocardium. This network has multiple functions which includes a preservation of tissue architecture and chamber geometry. Given its tensile strength, collagen is a major determinant of tissue stiffness. Its disproportionate accumulation, in the form of either a reactive or a reparative fibrosis, further increases stiffness. A degradation of collagen tethers, on the other hand, is an anatomic requisite for a distortion in tissue architecture and a reduction in stiffness that can lead to chamber dilatation, wall thinning, and even rupture of the myocardium. Collagen turnover in the myocardium is dynamic. When synthesis exceeds degradation, an adverse accumulation of collagen appears to distort tissue structure. This is true for either the hypertrophied and/or nonhypertrophied ventricle. Factors that contribute to the appearance of myocardial fibrosis are largely different from those that promote cardiac myocyte growth. Included amongst these fibrogenic factors are effector hormones of the reinin-angiotensin-aldosterone system (RAAS). Studies conducted both in intact animals (relative to dietary sodium intake) and in cultured adult cardiac fibroblasts have pointed toward the association between collagen accumulation and chronic elevations in circulating angiotensin II and aldosterone. A tissue hormonal system involving angiotensin II, endothelins and bradykinin, may likewise regulate fibrogenesis. In this regard, angiotensin converting enzyme is found in connective tissue of the normal heart, including the matrix of heart valves and the adventitia of the intramural coronary arteries, and fibrous tissue that forms following infarction or with chronic RAAS activation. The importance of ACE in the regulation of local angiotensin II and bradykinin levels and their contribution to collagen turnover is a fruitful area of research with important clinical implications. The myocardium also contains a proteolytic system, including collagenase. The characteristics and regulation of matrix metalloproteinases and their tissue inhibitors in various cardiovascular disease states requires further investigation.
J Mol Cell Cardiol 1994 Mar
PMID:Collagen network of the myocardium: function, structural remodeling and regulatory mechanisms. 802 11

Angiotensin-converting enzyme (ACE; EC 3.4.15.1) may participate in respiratory inflammatory diseases by regulating levels of inflammatory peptides such as bradykinin. The presence of ACE in the human nasal mucosa and in nasal secretions was determined by immunohistochemistry, measures of enzyme activity, and immunoblot. ACE activity was significantly more abundant in the membrane-rich fraction than in the soluble cytosolic fraction of nasal mucosal extracts (74.18 +/- 24.50 versus 3.99 +/- 1.83 pmol/min/mg protein, respectively, P < 0.01 by an enkephalin degradation assay; 89.16 +/- 16.17 versus 2.30 +/- 0.89 mU/mg protein, P < 0.01 by colorimetric assessment of Bz-Gly-Gly-Gly degradation). Topical application of histamine stimulated secretion of ACE activity into nasal lavage fluid (2.90 +/- 0.88 versus 1.53 +/- 0.45 U/liter after saline provocation, P < 0.05 by Bz-Gly-Gly-Gly assay). Allergen challenge also induced nasal secretion of ACE. In both histamine and allergen challenges, ACE release correlated closely with that of the vascular proteins IgG and albumin. Methacholine, a stimulant of glandular secretions, failed to augment ACE levels above baseline. ACE-immunoreactive material was localized by the immunogold technique with silver enhancement to the glycocalyx, between epithelial cells, and to interstitial, extracellular sites in the superficial lamina propria, with the highest intensity of staining immediately beneath the basement membrane. Some ACE was detectable in the mucus material of gland and duct lumens but not in gland cells themselves. Endothelial cells and some interstitial mononuclear cells also stained for ACE. ACE was identified by immunoblotting as a 150 kD band on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1994 Aug
PMID:Angiotensin-converting enzyme in the human nasal mucosa. 804 77

The coronary vascular effect of atrial natriuretic peptide is controversial: Coronary vasodilator as well as constrictor effects have been reported. The controversy may originate from interference of atrial natriuretic peptide with the renin-angiotensin system and/or tachyphylaxis of the effect of atrial natriuretic peptide. The effect of alpha-human atrial natriuretic peptide bolus application on changes of coronary flow was examined in the isolated, constant-pressure perfused rat heart. Six groups were considered: (1) control group; groups in which the renin-angiotensin system was modulated by pretreatment with continuous infusion of: (2) angiotensin II, (3) the angiotensin converting enzyme inhibitor captopril (4) the angiotensin II receptor blocker saralasin; and groups in which tachyphylaxis was examined by pretreatment with ANP, (5) as continuous infusion and (6) as bolus application. First, in control hearts, dose-response curves were obtained for single ANP dosages of 1-100 nmol. The effect of high dosages (40 and 100 nmol) was biphasic, with an initial vasodilator and subsequent long-lasting vasoconstrictor component. Hearts in which coronary flow was reduced by approximately 18% through continuous angiotensin II infusion showed an enhanced early vasodilator response after ANP administration, whereas the vasoconstrictor effect was no longer observable. Angiotensin converting enzyme inhibition and angiotensin II receptor blockade reduced the vasodilator effect of ANP. In addition, saralasin nearly abolished ANP-induced vasoconstriction, whereas vasoconstriction was unaltered by pretreatment with captopril. Captopril or saralasin alone did not change coronary flow, heart rate and left ventricular developed pressure. In groups (5) and (6). ANP bolus application showed significantly reduced vasomotor activity. We conclude that in the isolated rat heart. ANP has a biphasic effect with early vasodilation and late vasoconstriction. Both effects can be modulated by inhibition of the renin-angiotensin system at different levels indicating that vasomotor ANP effects result from interaction of ANP with the local renin-angiotensin system. ANP effects can be markedly reduced by tachyphylaxis.
J Mol Cell Cardiol 1994 Apr
PMID:Interrelation of coronary effects of atrial natriuretic peptide and the renin-angiotensin system in the isolated perfused rat heart. 807 8

We evaluated, firstly, the sensitivity to cardiac ischemic ATP breakdown during the development of hypertension and cardiac hypertrophy in Spontaneously Hypertensive Rats (SHR) v Wistar Kyoto (WKY) controls, and secondly, the effects of short-term (8 days) and prolonged (3 months) antihypertensive treatment with the angiotensin converting enzyme inhibitor enalapril on hypertrophy and sensitivity to global ischemia. In isolated perfused hearts, ischemia was induced by a stepwise lowering of the perfusion pressure and the appearance of the ATP breakdown products (purines) in the coronary effluent was assessed as a measure of ischemia. Hearts from 2.5- and 4-month-old SHR started to release purines at a higher perfusion pressure than hearts of WKY, associated with a higher maximum concentration in the coronary effluent. This increased ischemic ATP breakdown in 2.5- and 4-month-old SHR could be attributed to a decreased flow at a given perfusion pressure, because of a two-fold increase in coronary vascular resistance (CVR). In contrast, the maximal purine concentration in the coronary effluent in hearts of 7-month-old SHR was reduced compared to the younger SHR and only slightly higher than 7-month-old WKY, despite a persistent increase in CVR. Enalapril normalized the blood pressure, but only prolonged treatment, significantly prevented and regressed cardiac hypertrophy, and reduced CVR. Whereas enalapril did not influence ATP breakdown in WKY, in SHR both short- and long-term treatment normalized it to the pattern observed in WKY. We conclude that during the early phase of cardiac hypertrophy the hearts of SHR become more sensitive to ischemic ATP breakdown solely because of an increase in CVR, whereas during the established hypertrophic phase, the hearts appear to adapt metabolically, resulting in normalized purine release. Enalapril normalized the transient increase in sensitivity to ischemic ATP breakdown during the development of hypertension in SHR, independent of effects on cardiac hypertrophy, apparently by improving coronary flow at low perfusion pressures.
J Mol Cell Cardiol 1994 May
PMID:Age-related increase in sensitivity for ischemic ATP breakdown in hypertrophic hearts of SHR normalized by enalapril. 807 19

Utilization of highly enriched preparations of steroidogenic Leydig cells have proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. However, recent work indicates that isolated Leydig cells are often subjected to oxygen (O2) toxicity when cultured at ambient (19%) oxygen concentrations. Because intracellular antioxidants play an important role in protecting cells against oxygen toxicity, we have investigated the intracellular antioxidant defense system of isolated Leydig cells. The cellular levels of several antioxidants including catalase, glucose-6-phosphate dehydrogenase (G-6-PDH), superoxide dismutase (SOD) of the Cu/Zn & Mn variety, glutathione peroxidase, glutathione reductase and total glutathione were quantitated using enriched populations of Leydig cells isolated from adult male guinea pig testes. Compared to whole testicular homogenates, Leydig cells contained significantly (P < 0.01) less G-6-PDH, total SOD, glutathione reductase and total glutathione, but significantly (P < 0.001) more glutathione peroxidase. Compared to hepatic values previously reported in the guinea pig, Leydig cells contain nearly 400 times less catalase, about 14 times less glutathione peroxidase and almost 11 times less glutathione reductase. Since G-6-PDH and glutathione reductase are both necessary to regenerate reduced glutathione (GSH) which couples with glutathione peroxidase to breakdown hydrogen peroxide (H2O2) under normal conditions, it is plausible that the oxygen toxicity observed in isolated Leydig cells is due to the intracellular accumulation of H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1993 Sep 08
PMID:The antioxidant defense system of isolated guinea pig Leydig cells. 810 85

To investigate the contribution of the cardiac renin-angiotensin system to ventricular dilatation after myocardial infarction, we examined the effects of 3-week treatments with an angiotensin converting enzyme inhibitor, delapril, and a selective angiotensin II type 1 (AT1) receptor antagonist, TCV-116, on haemodynamics and ventricular angiotensin II contents in myocardial-infarcted rats. TCV-116 reduced mean aortic pressure, and prevented the increase of right and left ventricular weight, left ventricular end-diastolic pressure and volume of myocardial-infarcted rats, to a similar extent to delapril. Thus, AT1 receptor-mediated action of angiotensin II plays a central role in the development of ventricular dilatation. Angiotensin II contents in the right and non-infarcted left ventricles (6.0 +/- 1.0 and 5.9 +/- 0.7 pg/g tissue, respectively, mean +/- S.E.M.) of myocardial-infarcted rats were not different from those of sham-operated rats. However, angiotensin II contents in the infarcted scar (21.7 +/- 3.5 pg/g) of myocardial-infarcted rats were 4.2-fold higher than those in the left ventricle of sham-operated rats. Delapril reduced angiotensin II contents in the right and non-infarcted left ventricles, and the scar by 48, 81 and 60%, respectively, but did not reduce plasma angiotensin II in myocardial-infarcted rats. TCV-116 also decreased angiotensin II in the right and non-infarcted left ventricles by 57 and 56%, respectively, while increased plasma angiotensin II by 4.3-fold. Thus, the prevention of ventricular dilatation by these two agents was associated with the decrease in ventricular angiotensin II contents. These observations suggest that the cardiac renin-angiotensin system rather than the circulating system may play an important role in ventricular dilatation after myocardial infarction.
J Mol Cell Cardiol 1993 Nov
PMID:Contribution of cardiac renin-angiotensin system to ventricular remodelling in myocardial-infarcted rats. 830 70

We present the application of free energy perturbation theory/molecular dynamics to predict the consequence of replacing each of the seven peptide bonds in the potent HIV protease inhibitor JG365: ACE (acetyl)-Ser-Leu-Asn-HEA (hydroxyethylamine analog of Phe-Pro)-Ile-Val-NME (N-methyl) by ethylene or fluoroethylene isosteres. Replacing two of these bonds may well lead to significantly tighter binding; replacing two others is predicted to significantly diminish the binding affinity. Also, for three of the peptide bonds fluoroethylene replacements could lead to increased binding of free energies of the inhibitors. Our results should be considered as predictive since there are, as yet, no experimental results on such peptide replacements as enzyme inhibitors.
J Comput Aided Mol Des 1993 Jun
PMID:Peptide mimetics as enzyme inhibitors: use of free energy perturbation calculations to evaluate isosteric replacement for amide bonds in a potent HIV protease inhibitor. 837 26

The gene encoding the testis isozyme of angiotensin-converting enzyme (testis ACE) is one example of the many genes expressed uniquely during spermatogenesis. This protein is expressed by developing germ cells late in their development and results from the activation of a sperm-specific promoter that is located within intron 12 of the gene encoding the somatic isozyme of ACE. In vitro transcription, DNase footprinting, gel shift assays, and transgenic mouse studies have been used to define the minimal testes ACE promoter and to characterize DNA-protein interactions mediating germ cell-specific expression. These studies show that proper cell- and stage-specific expression of testis ACE requires only a small portion of the immediate upstream sequence extending to -91. A critical motif within this core promoter is a cyclic AMP-responsive element sequence that interacts with a testis-specific transactivating factor. Since this putative cyclic AMP-responsive element has been conserved within the testis ACE promoters of different species and is found at the same site in other genes that are expressed specifically in the testis, it may provide a common mechanism for the recognition of sperm-specific promoters.
Mol Cell Biol 1993 Jan
PMID:Sperm-specific expression of angiotensin-converting enzyme (ACE) is mediated by a 91-base-pair promoter containing a CRE-like element. 838 Feb 20

Cardiac hypertrophy in rats was produced by aortic banding for 6 weeks and regression of hypertrophy in these experimental animals was induced by administration of angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) for 6 weeks. The left ventricular muscle mass and systolic pressure were decrease upon treating the hypertrophied rats with enalapril. This drug also decreased the number of alpha 1-adrenoceptors in hypertrophied myocardium without any changes in beta-adrenoceptors. The regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril for 10 weeks was not associated with any alterations in alpha 1-adrenoceptors in hypertrophied myocardium, but was decreased in beta-adrenoceptors. Effects of enalapril on extracellular matrix in the myocardium was also observed in regression of hypertrophy in which the type III collagen mRNA expression and collagen contents were reduced in comparison with those of hypertrophied myocardium. These results indicate that regression of cardiac hypertrophy is not always associated with a decrease in the number of alpha 1-adrenergic receptors and that the beneficial effects of enalapril in the hypertrophied heart in aortic banding animals may be of some specific nature.
Mol Cell Biochem 1993 Feb 17
PMID:Effect of angiotensin converting enzyme inhibitor on regression in cardiac hypertrophy. 838

Angiotensin I converting enzyme (ACE) is a dipeptidyl carboxypeptidase synthesized by endothelial cells from many vascular beds as well as by extravascular tissues. Two forms of ACE have been characterized, a pulmonary form and a testicular form. Previously, in the gastrointestinal tract, we localized ACE in the rabbit gastric fundic tissue. In the present study, Northern blot analysis demonstrated the expression of a 5 kb ACE mRNA in fundic mucosa, identical in size to pulmonary ACE mRNA. In order to confirm the epithelial origin of this ACE, we have purified fundic epithelial cells by a flow cytometry technique by which endothelial cells were excluded and the population was enriched in intermediate and chief cells. Using reverse transcription and polymerase chain reaction with specific oligonucleotides, we have amplified from the enriched fundic epithelial cell RNA a 874 bp fragment, the restriction map of which is identical to that of rabbit lung. These findings demonstrate that in gastric mucosa ACE is expressed in fundic epithelial cells and seems to be similar to the pulmonary form.
Mol Cell Endocrinol 1993 Apr
PMID:Expression of angiotensin I converting enzyme mRNA in rabbit gastric epithelial cells. 839 87


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