Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a prospective study, Type III procollagen N-terminal peptide was measured in the sera of 38 subjects with biopsy-proven pulmonary sarcoidosis at 6-month intervals over a period of 5 yr. The subjects were divided into four groups according to their radiologic presentation and clinical course: Group A (n = 10) subjects with sarcoidosis Type I without radiologic progression over 5 yr; Group B (n = 5) subjects with sarcoidosis Type I with radiologic progression to Stage II or III; Group C (n = 9) subjects with sarcoidosis Types II and III without progression over 5 yr; and Group D (n = 14) subjects with sarcoidosis Types II and III with radiologic progression. Lung function tests (FVC, FEV1, and DLCO), chest roentgenograms, and measurements of serum angiotensin converting enzyme (S-ACE) were performed concurrently with the S-PCP-III levels. Significantly higher levels of S-PCP-III were found in group B (Type I, progressive) (18.2 +/- 1.09 ng/ml) and in group D (Type II/III, progressive) (13.9 +/- 1.2 ng/ml) compared with those of Group A (Type I, stable) (9.1 +/- 1.09 ng/ml) and Group C (Type II/III, stable) (7.6 +/- 1.1 ng/ml) or normal volunteers (9.4 +/- 4 ng/ml) (p less than 0.001 for all comparisons). Changes in S-PCP-III levels tended to parallel the clinical course, and steroid treatment resulted in a significant decrease in S-PCP-III concentrations (p less than 0.001). In contrast, serum angiotensin converting enzyme (S-ACE) levels did not correlate with either the clinical course or radiologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum procollagen III peptide levels in subjects with sarcoidosis. A 5-year follow-up study. 131 May 76

Changes in our concepts of angiotensin I converting enzyme are reviewed briefly. The actions of this enzyme go beyond liberating angiotensin II from angiotensin I or inactivating bradykinin. Its very wide distribution in the body and its activity in vitro indicate involvement in the metabolism of other biologically active peptides. The recent molecular cloning of the human enzyme confirmed the existence of a hydrophobic C-terminal peptide that forms the short transmembrane domain of this plasma membrane-bound enzyme. The much longer external portion contains two homologous active site domains but probably only one functional active center. Finally, in spite of the great progress made in studying angiotensin converting enzyme, there are many challenging problems waiting to be solved.
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PMID:Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. 217 Feb 73

Type III procollagen N-terminal peptide was not detectable in bronchoalveolar lavage fluid from healthy volunteers but was present in fluid from the majority of patients with pulmonary sarcoidosis (N = 110); the mean concentration was 0.6 micrograms/liter returned fluid, range less than or equal to 0.2 to 19.5 or, expressed in relation to the amount of albumin recovered, 9.5 mg/gm albumin (range less than or equal to 1 to 45). The serum concentrations in the patients with sarcoidosis were normal. Significant inverse correlations were found between lavage fluid procollagen peptide and vital capacity (p less than 0.001), forced expiratory volume (p less than 0.01), and diffusion capacity (p less than 0.01). Lavage fluid procollagen peptide was also related to pulmonary radiological findings (p less than 0.001) and serum levels of angiotensin converting enzyme (p less than 0.001). These findings support the hypothesis that procollagen peptide in lavage fluid is a potential marker of activated pulmonary fibroblasts or an expanded fibroblast mass associated with interstitial lung fibrosis.
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PMID:Procollagen III peptide in bronchoalveolar lavage fluid. A potential marker of altered collagen synthesis reflecting pulmonary disease in sarcoidosis. 302 50

Laminin is a noncollagenous component of the extracellular matrix in the alveolar wall and may play a role in the development of fibrotic lung disease. Serum levels of laminin fragment P1 as well as procollagen III peptide were determined in 28 patients with pulmonary sarcoidosis and 10 healthy controls using specific radioimmunoassays. The patients' results were compared with the clinical appearance, lung function values (vital capacity, total lung capacity, FEV1, transfer coefficient (KCO), and alveolar-arterial oxygen difference during exercise) and serum concentrations of angiotensin converting enzyme and soluble interleukin 2 receptor. Laminin levels in patients were significantly higher than in controls but always remained within normal limits. Although there was a tendency towards higher values in patients with active disease and with radiographic involvement, no significant correlation was found between laminin concentration and clinical, functional or biochemical data. In contrast, procollagen III N-terminal peptide concentrations were elevated in 19 of 28 patients and showed a weak but significant inverse correlation with parameters of restriction with significantly higher values in patients with active disease. In conclusion, serum levels of laminin fragment P1 are not elevated in pulmonary sarcoidosis and do not correlate with other parameters of the disease. Yet serum levels of procollagen III N-terminal peptide were associated with the degree of parenchymal involvement as expressed by functional disturbance and with active disease.
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PMID:Laminin fragment P1 in the sera of patients with pulmonary sarcoidosis. 889 82

Angiotensin I-converting enzyme (ACE, kininase II) has 2 active domains (N and C) in a single peptide chain. Because we found its N-domain more stable than its C-domain, we investigated the effect of the amino-terminus of human ACE on the C-domain with a molecular construct expressed in Chinese hamster ovary cells (CHO) cells and transiently in HEK293 cells. This active N-deleted ACE contained only the first 141 amino acids of the human N-domain but not its active center and was linked to the active C-domain containing the transmembrane and cytosolic portions of ACE. The CHO cells were also transfected with human B(2) bradykinin receptor. ACE inhibitors (5 nmol/L or 1 micromol/L) augmented bradykinin (100 nmol/L) effects, elevated B(2) receptor numbers, and resensitized the receptor desensitized by agonist as measured by arachidonic acid release or [Ca(2+)](i) mobilization. Arachidonic acid release was mediated by pertussis toxin-sensitive G alpha(i), and [Ca(2+)](i) mobilization was mediated by pertussis-insensitive G alpha(q) protein receptor complex. The properties of the construct were compared with wild-type ACE and separate N- and C-domains. The N-deleted ACE differed from wild-type in activation by Cl(-) and [SO(4)](2-) ions, hydrolysis ratios of substrates (both short synthetic and endogenous peptides) and heat stability. Thus, the N-terminal peptide of ACE affected the characteristics of the C-domain active center. ACE inhibitors acting on N-deleted ACE, which had only a single C-domain active center anchored to plasma membrane, induced cross-talk between the enzyme and the B(2) receptor (eg, the inhibitors resensitized the receptor) independent of blocking bradykinin inactivation.
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PMID:Effects of the N-terminal sequence of ACE on the properties of its C-domain. 1090 22

Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure.
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PMID:Treatment of congestive heart failure: interfering the aldosterone-cardiac extracellular matrix relationship. 1171 28

Heart failure, the common end-point of many cardiac diseases, is a major contributor to mortality and morbidity and contributes considerably to health care costs. Current treatment regimens include beta-adrenergic antagonists, angiotensin converting enzyme inhibitors, and inotropic agents are used by some patients. Studies in experimental animals have demonstrated that inhibition of signaling pathways downstream of the heterotrimeric G protein Gq reduce ventricular hypertrophy and protects from the development of heart failure. However, targets identified, to date, have been limited by a lack of tissue specificity. In cardiomyocytes, Gq activates only one splice variant of one subtype of phospholipase Cbeta, specifically phospholipase Cbeta1b (PLCbeta1b) and PLCbeta1b is responsible for Gq mediated hypertrophic and apoptotic responses. PLCbeta1b targets to the sarcolemma via its unique C-terminal sequence and its activation can be inhibited by expressing the C-terminal sequence to compete for sarcolemmal binding. Inhibition of PLCbeta1b by the C-terminal peptide reduces hypertrophic responses in cardiomyocytes. We present the evidence that inhibition of the sarcolemmal association of PLCbeta1b provides a cardiac-specific target for the development of drugs to reduce pathological cardiac hypertrophy and thereby to reduce the burden of heart failure.
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PMID:Potential treatment of cardiac hypertrophy and heart failure by inhibiting the sarcolemmal binding of phospholipase Cbeta1b. 2042 66