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

An endogenous ACE activator has been revealed. Neutrophil-enriched human leucocyte preparations released in isotonic media a relatively thermostable factor, capable of increasing the angiotensin-converting enzyme activity 1.6-2.0-fold. Activator would not pass through a 30 kDa cutoff membrane. Data on the presence of the activator in vivo were obtained in studies of protein-free serum fractions of patients with a hereditary CI-esterase inhibitor deficiency. It was suggested that the neutrophil-released ACE activator could have a role in the modulation of the inflammatory response.
Biochem Mol Biol Int 1993 Jul
PMID:Angiotensin-converting enzyme activator from purified human neutrophils. 840 24

The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of the descending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasystoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system does not play a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was found in vitro as well as in vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radical scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established.
Mol Cell Biochem 1993 Feb 17
PMID:Cardioprotective actions of wild garlic (allium ursinum) in ischemia and reperfusion. 845 76

The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/- 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass.
J Mol Cell Cardiol 1993 Feb
PMID:Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure. 847 26

Human PDH complex deficiency is an extremely heterogeneous disease in its presentation and clinical course. In an investigation at the level of the gene into ten cases of PDH complex (E1) deficiency, we found that all had mutations in the coding sequence of the X-linked E1 alpha gene while the E1 beta coding sequence was normal. Six of these patients (three males, three females) had missense mutations resulting in a changed amino acid residue in the E1 alpha subunit at positions amino acid 148 (in two siblings), 170, 202, 234 and 263 of the mature protein. Two of the females had one normal E1 alpha gene and one with a deletion at the sites of tandem repeats of AGTAAGA and TAT respectively. The two remaining females also had one normal E1 alpha gene and one with an insertion. Both insertions, one of 2 bp and one of 4 bp, occurred in DNA hotspots normally associated with deletions. Only two of these ten mutations have been reported in other patients previously. In the five cases (including the two siblings) where parent DNA was available, only in one case could the same mutation be found in the patient as well as the maternal genomic DNA.
Hum Mol Genet 1993 Apr
PMID:Mutations in the X-linked E1 alpha subunit of pyruvate dehydrogenase leading to deficiency of the pyruvate dehydrogenase complex. 850 6

A protein, Bm91, which was first identified as a protective vaccine antigen from the tick Boophilus microplus, has regions of very strong amino acid sequence similarity to mammalian carboxydipeptidases or angiotensin converting enzymes (ACE; E.C. 3.4.15.1). This protein is now shown to share many biochemical and enzymatic properties with mammalian carboxydipeptidases. It is enzymatically active in a conventional assay for ACE using hippuryl-Gly-Gly as substrate. The hydrolysis of the C-terminal nonapeptide of the insulin B chain proceeds by sequential removal of carboxy-terminal dipeptides. The similarities extend to the dependence of activity on pH and added salt. Bm91 is inhibited by two well-characterized inhibitors of the mammalian enzymes, the drug Captopril and a nonapeptide, and the inhibition occurs in similar concentration ranges to those effective with the mammalian enzymes. However, the natural substrates of the tick enzyme are unknown. Angiotensin I itself is a poor substrate and the enzyme's natural substrates are likely to be one or more of the pharmacologically active peptides occurring in insects and arthropods.
Insect Biochem Mol Biol 1995 Oct
PMID:Carboxydipeptidase from Boophilus microplus: a "concealed" antigen with similarity to angiotensin-converting enzyme. 854 86

Although pharmacological therapy with angiotensin converting enzyme (ACE) inhibitors has proved to be effective in patients with heart failure (HF), the experimental basis of this effect has not yet been addressed. In the present study, animals with HF were treated with an oral administration of 10 mg/kg/day captopril, 10 mg/kg/day enalapril and 3 mg/kg/day trandolapril from the 2nd to 12th week after the operation. HF was induced by permanent occlusion of the left coronary artery of the rat at 2 mm from its origin. Treatment of the HF rats with the ACE inhibitors enhanced the decrease in mean arterial blood pressure, attenuated the rise in left ventricular end-diastolic pressure, an indirect marker of preload, and diminished the reduction in cardiac output and stroke volume indices of the HF animal. Treatment also reversed the reduction in ATP, creatine phosphate, creatine and the mitochondrial oxygen consumption rate of the viable left and right ventricles of the HF animal. The improvement of the cardiac output index and high-energy phosphate levels of the HF rat by the ACE inhibitors was associated with the recovery of the mitochondrial oxygen consumption rate. In sham-operated animals, treatment with the ACE inhibitors reduced mean arterial pressure and left ventricular systolic pressure, but not metabolic variables concerning myocardial energy metabolism. The present results provide evidence that ACE inhibitor therapy improves cardiac function and myocardial energy metabolism of experimental animals with chronic heart failure. The mechanism underlying the benefit of long-term treatment with ACE inhibitors is probably attributable to recovery or preservation of the mitochondrial function and reduction in preload.
J Mol Cell Cardiol 1995 Oct
PMID:Effects of long-term therapy with ACE inhibitors, captopril, enalapril and trandolapril, on myocardial energy metabolism in rats with heart failure following myocardial infarction. 857 37

The effects of L-carnitine on 14CO2 release from [1-14C]pyruvate oxidation (an index of pyruvate dehydrogenase activity, PDH), [2-14C]pyruvate, and [6-14C]glucose oxidation (indices of the acetyl-CoA flux through citric acid cycle), and [U-14C]glucose (an index of both PDH activity and the flux of acetyl-CoA through the citric acid cycle), were studied using isolated rat cardiac myocytes. L-carnitine increased the release of 14CO2 from [1-14C]pyruvate, and decreased that of [2-14C]pyruvate in a time and concentration-dependent manner. At a concentration of 2.5 mM, L-carnitine produced a 50% increase of CO2 release from [1-14C]pyruvate and a 50% decrease from [2-14C]pyruvate oxidation. L-carnitine also increased CO2 release from [1-14C]pyruvate oxidation by 35%, and decreased that of [2-14C]pyruvate oxidation 30%, in isolated rat heart mitochondria. The fatty acid oxidation inhibitor, etomoxir, stimulated the release of CO2 from both [1-14]pyruvate and [2-14C]pyruvate. These results were supported by the effects of L-carnitine on the CO2 release from [6-14C]- and [U-14C]glucose oxidation. L-carnitine (5 mM) decreased the CO2 release from [6-14C]glucose by 37%, while etomoxir (50 microM) increased its release by 24%. L-carnitine had no effect on the oxidation of [U-14C]glucose. L-carnitine increased palmitate oxidation in a time- and concentration-dependent manner in myocytes. Also, it increased the rate of efflux of acetylcarnitine generated from pyruvate in myocytes. These results suggest that L-carnitine stimulates pyruvate dehydrogenase complex activity and enhances non-oxidative glucose metabolism by increasing the mitochondrial acetylcarnitine efflux in the absence of exogenous fatty acids.
J Mol Cell Cardiol 1995 Nov
PMID:Stimulation of non-oxidative glucose utilization by L-carnitine in isolated myocytes. 859 97

Factors that influence the development of the normal pulmonary vasculature are poorly understood. Since increased local production of angiotensin II (AII) by angiotensin converting enzyme (ACE) has been implicated in the medial hypertrophy of systemic and pulmonary hypertension, we questioned whether ACE and angiotensin receptor expression may influence the muscularization of the normal pulmonary vasculature during development. The approach employed measurement of lung ACE activity, assessment of local ACE expression by immunohistochemistry, and angiotensin type 1 receptor (AT1) expression by in situ hybridization in rat lungs ranging from 15 days of intrauterine life (term = 21 d) to adulthood. The temporal and spatial pattern of ACE expression was compared with that of the endothelial marker, von Willebrand factor (vWF), and the smooth muscle cell markers, alpha smooth muscle actin and smooth muscle myosin. ACE activity was first detected in lung homogenates on day 17 of gestation (1 +/- 0.2 mU/mg) and increased progressively to term (27.7 +/- 3.2 mU/mg). However, the greatest increase in lung ACE activity to adult levels (379 +/- 25.2 mU/mg) occurred between 2 and 4 wk of postnatal life. Immunohistochemistry demonstrated vWF expression by vascular endothelium throughout the lung as early as day 15 of gestation. In contrast, ACE expression was observed in the endothelium of only hilar pulmonary arteries on day 15 of gestation, and thereafter was noted to be expressed in endothelial cells of progressively more distal arteries, such that by term, endothelial cells of all muscularized arteries expressed ACE. Alveolar capillary ACE expression was not detected until day 20 of gestation, and increased dramatically after birth. Smooth muscle actin expression in lung arteries closely paralleled the expression of endothelial ACE. AT1 receptor mRNA was first expressed in the peripheral lung on day 17 of gestation by non-epithelial undifferentiated mesenchyme. In contrast, AT1 mRNA signal was much reduced in differentiated smooth muscle. We speculate that ACE expression in the fetal lung circulation may influence the muscularization of fetal pulmonary arteries by the interaction of locally produced angiotensin II with the AT1 receptor.
Am J Respir Cell Mol Biol 1996 Jun
PMID:Developmental regulation of angiotensin converting enzyme and angiotensin type 1 receptor in the rat pulmonary circulation. 865 81

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, DNA, protein and myosin isoform pattern in sham and hypertrophied rats. AAC increased the mean arterial pressure (MAP) and systolic blood pressure (SBP), and resulted in increased left ventricle/body weight ratio, LV thickness, RNA and protein content, however total DNA was not changed. The expression of fetal isogene, beta-myosin heavy chain (beta-MHC), was markedly enhanced where as alpha-MHC was reduced. High-dose captopril (100 mg/kg p.o.,) significantly prevented the increase in haemodynamics, development of LVH, LV remodeling, increase in total protein, RNA and antithetical expression of myosin isoforms. Hydralazine (15 mg/kg p.o.,), did not modulate hypertrophic changes and low-dose captopril (1.5 mg/kg p.o.,) which has not produced any marked fall in MAP and SBP also modulated favourably the development of LVH and its biochemical markers. Thus, the prevention of the development of LVH and induction of beta-MHC by non-hypotensive doses of captopril may be related to the blockade of intracardiac production of angiotensin II rather than circulating system. These results suggest that cardiac RAS may play an important role in pressure overload induced LVH.
Mol Cell Biochem 1996 Feb 09
PMID:Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction. 871 33

1. Angiotensin II is a well-known vasopressive octapeptide that is the principal end-product of the renin-angiotensin system. In addition to its tonic effect on vascular smooth muscle cells, it also stimulates aldosterone secretion from the adrenals and promotes sodium reabsorption through renal tubular cells. 2. These physiological functions have been appreciated for some time, but as details of the molecular and cell biology of the angiotensin response mechanism become understood, it is increasingly apparent that the hormone has a much broader repertoire. Its functional variability is made possible by (i) different enzymatic routes for its generation, (ii) different receptors distributed in different tissues, (iii) different mechanisms for receptor regulation, and (iv) different signal transduction pathways. 3. This insight is the direct consequence of advances in pharmacology that led first to inhibitors of angiotensin converting enzyme and later to angiotensin II receptor antagonists. This review looks at the current status of angiotensin biochemistry and physiology and provides a basis for anticipation of future developments.
Cell Mol Neurobiol 1995 Dec
PMID:Angiotensin II: biosynthesis, molecular recognition, and signal transduction. 871 34


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