Angiotensin I-converting enzyme inhibitory peptides in red-mold rice made by Monascus purpureus

The ACE inhibitory activity in red-mold rice extracts, prepared from 24 strains of the genus Monascus, was measured. The most effective strain for ACE inhibition was Monascus purpureus IFO 4489 (IC₅₀ = 0.71 mg/ml). Although the antihypertensive substance γ-amino butyric acid was detected in the red-mold rice (85.2 mg/kg), it did not contribute to ACE inhibition. Four ACE inhibitory peptides were isolated from the extract and identified as Ile-Tyr (IC₅₀ = 4.0 μM), Val-Val-Tyr (22.0 μM), Val-Phe (49.7 μM) and Val-Trp (3.1 μM) by protein sequencing. The ACE inhibitory activity of these peptides was almost completely preserved after successive in vitro digestion by pepsin, chymotrypsin and trypsin. These results suggest that red-mold rice made by M. purpureus could be useful in alleviating hypertension.     

Characterization and activity of angiotensin-converting enzyme in Holstein semen

The study was designed to perform immunodetection in spermatozoa and seminal plasma, immunolocalization in spermatozoa, and evaluation of the enzymatic activity of angiotensin-converting enzyme (ACE) in the semen of Holstein bulls. We used ejaculates from five bulls as part of a regular collection of semen. The monoclonal anti-ACE antibody recognized a single protein band with 100 kDa in detergent extract prepared from sperm and in seminal plasma. ACE enzymatic activity in sperm was 43.7, 21.3, 45.6, 60.0, and 57.7 mU/mL in bulls 1, 2, 3, 4, and 5, respectively, and 0.3, 2.3, 3.0, 2.3, and 2.6 mU/mL in seminal plasma of the same bulls, respectively. The average percentages of sperm with acrosome reactions after treatment with heparin were 28.3%, 28.6%, 35.2%, 25.0%, and 32.3%, respectively. These values were higher than the percentages of acrosome reactions in controls and the captopril group (P<0.05), although no difference was seen between the captopril and control groups (P>0.05). After 4h of incubation, motility in the control group (32.9%) was significantly higher than that in the heparin (15.7%) and captopril (12.1%) groups. No difference was found in motility after the capacitation assay in the heparin and captopril groups (P>0.05). In conclusion, ACE was immunologically localized in the acrosome of the spermatozoa of Holstein bull, the specific enzymatic activity of ACE in detergent-extracted spermatozoa and seminal plasma was inhibited by captopril, and this ACE inhibitor reduced the percentage of sperm with progressive motility and acrosome reactions after capacitation in vitro.     

Angiotensin-converting enzyme and anorexia nervosa

Angiotensin-converting enzyme (ACE) activity was measured in 10 patients with anorexia nervosa, 6 with hyperthyroid Graves' disease, and 7 with primary hypothyroidism. Patients with anorexia nervosa had a low serum ACE activity (9.8 +/- 2.2 IU/l), as compared to findings in normal subjects (13.4 +/- 3.5 IU/l) (P less than 0.05). Patients with hyperthyroid Graves' disease had high serum ACE activity (23.7 +/- 5.8 IU/l), as compared to levels in normal subjects (P less than 0.01), and patients with primary hypothyroidism tended to have low serum ACE activity (10.1 +/- 1.8 IU/l), compared to the normal subjects (P less than 0.1). Following weight gain (before; 71.3 +/- 10.2% of ideal body weight, after; 88.7 +/- 5.6% of ideal body weight), serum ACE activity in patients with anorexia nervosa reverted to within the normal range (13.8 +/- 3.5 IU/l), and serum T3 concentration was restored to the normal range (before; 0.7 +/- 0.2 ng/ml, after; 1.1 +/- 0.3 ng/ml). In these patients, ACE activity correlated with the per cent of ideal body weight (P less than 0.05). These data suggest that, in underweight subjects with anorexia nervosa, decreased serum ACE activities may relate to emaciation.     

Apoptosis of Hepatocellular Carcinoma Cells Induced by Nanoencapsulated Polysaccharides Extracted from Antrodia Camphorata

Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G₁ phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells.     

ACE activity during the hypotension produced by standardized aqueous extract of Cecropia glaziovii Sneth: A comparative study to captopril effects in rats

To evaluate the effect of the standardized aqueous extract (AE) of Cecropia glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1) activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive control on the same animals. The effects on the blood pressure were recorded directly from the femoral artery (single dose), or indirectly by the tail cuff method (repeated doses) in conscious rats. The plasma ACE activity was determined spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The arterial blood pressure, heart rate and plasma ACE activity were not significantly modified within 24 h after a single dose administration of AE. Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and heart rate was increased by 10-20% from 30 min to 24 h after drug administration. ACE activity after captopril presented a dual response: an immediate inhibition peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To correlate the drug effects upon repeated administration of either compound, normotensive rats were separated in three groups: animals with high ACE (48.8+/-2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/-0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg after 14 days. The hypotension was reversed upon washout 60 days afterwards. Likely, repeated captopril administration decreased blood pressure by 20 mm Hg throughout treatment in all groups. After 30 days treatment with AE (0.5 g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group. After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h in all groups. It is concluded that the hypotension produced by prolonged treatment with AE of C. glaziovii is unrelated to ACE inhibition.     

Optimization of submerged culture conditions for the production of angiotensin converting enzyme inhibitor from <Emphasis Type="Italic">Flammulina velutipes</Emphasis>

The angiotensin-converting enzyme (ACE) inhibitory effect was tested in the culture broth from submerged mycelial cultures of 20 basidiomycetes. The ACE inhibitory effect of culture broth from Flammulina velutipes strain 414 was the highest (52.8%), followed by Lentinus edodes strains 2 (44.4%) and 16 (41.3%). Nutritional requirements for the production of ACE inhibitory substance from F. velutipes were studied. Sucrose, ammonium acetate, and glutamic acid were chosen for the maximum production of ACE inhibitory substance. The optimal medium composition was (g/l): sucrose 20, ammonium acetate 5, glutamic acid 2, KH₂PO₄ 3, MgSO₄·7H₂O 0.8, and yeast extract 0.5. Under optimal culture conditions, the ACE inhibitory effect was more than 80%. Received 04 May 2002/ Accepted in revised form 11 June 2002     

植物雅龙果叶抑制ACE活性的研究

为研究植物雅龙果叶子降血压活性,利用HPLC对其50％丙酮．水提取物、正丁醇和水萃取部分及其从正丁醇萃取部分中分离得到的两种单一化合物进行了ACE抑制活性的检测。结果表明上述样品均具有一定的抑制ACE活性,50％丙酮-水提取物、正丁醇萃取部分以及芦丁和咖啡酸的EC50值分别为53、30、4．1、2．2mg／mL。     

Angiotensin I-converting enzyme inhibitory peptides isolated from tofuyo fermented soybean food

Angiotensin I-converting enzyme (ACE) inhibitory activity was observed in a tofuyo (fermented soybean food) extract with an IC(50) value of 1.77 mg/ml. Two ACE inhibitors were isolated to homogeneity from the extract by adsorption and gel filtration column chromatography, and by reverse-phase high-performance liquid chromatography (HPLC). The purified substances reacted with 2,4,6-trinitrobenzensulfonic acid sodium salt. The amino acid sequences of these inhibitors determined by Edman degradation were Ile-Phe-Leu (IC(50), 44.8 microM) and Trp-Leu (IC(50), 29.9 microM). The Ile-Phe-Leu sequence is found in the alpha- and beta-subunits of beta-conglycinin, while the Trp-Leu sequence is in the B-, B1A- and BX-subunits of glycinin from soybean. Both of the peptides are non-competitive inhibitors. The inhibitory activity of Trp-Leu was completely preserved after a treatment with pepsin, chymotrypsin or trypsin. Even after successive digestion by these gastrointestinal proteases, the activity remained at 29% of the original value.     

Angiotensin-converting enzyme activity in ovine bronchial vasculature.

Angiotensin-converting enzyme (ACE) plays a major role in the metabolism of bradykinin, angiotensin, and neuropeptides, which are all implicated in inflammatory airway diseases. The activity of ACE, which is localized on the luminal surface of endothelial cells (EC), has been well documented in pulmonary EC; however, few data exist regarding the relative activity of ACE in the airway vasculature. Therefore, we measured ACE activity in cultured EC from the sheep bronchial artery and bronchial mucosa (microvascular) and compared it with pulmonary artery EC. The baseline level of total ACE activity (cellular plus secreted) was significantly greater in bronchial microvascular EC (1.24 +/- 0.24 mU/106 cells) compared with bronchial artery EC (0.59 +/- 0.15 mU/106 cells; P < 0.05) and comparable to pulmonary artery EC (1.12 +/- 0.14 mU/106 cells; P > 0.05). Measured ACE activity secreted into culture medium for each cell type was 64-74% of total activity and did not differ among the three EC types (P = 0.17). Hydrocortisone (10 microg/ml; 48-72 h) treatment resulted in a significant increase in ACE activity in bronchial EC. Likewise, TNF-alpha (0.1 ng/ml) treatment markedly increased ACE activity in all cell lysates (P < 0.05). We confirmed the importance of ACE activity in vivo since, at the highest dose of bradykinin studied (10-8 M), bronchial artery pressure at constant flow showed a greater decrease after captopril treatment (36% before vs. 60% after; P = 0.05). These results demonstrate high ACE expression of the bronchial microvasculature and suggest an important regulatory role for ACE in the metabolism of kinin peptides known to contribute to airway pathology.     

一株高ACE抑制活性乳杆菌的筛选鉴定、培养条件优化及其基因组分析

【背景】乳杆菌是人体肠道益生菌,其发酵乳中可检测到血管紧张素转换酶(Angiotensin converting enzyme,ACE)抑制肽。海洋蕴藏着丰富的微生物种质资源,分布着大量的乳杆菌。【目的】从高通量测序结果中发现渤海沉积物中分布着乳杆菌资源。为了进一步开发具有ACE抑制活性的海洋乳杆菌资源,提高乳杆菌发酵乳的ACE抑制活性,筛选瑞士乳杆菌(Lactobacillus helveticus)并对其特性进行研究。【方法】采用高通量测序技术从渤海沉积物中检测乳杆菌,并对其进行富集分离,对筛选出的乳杆菌进行16S rRNA基因鉴定和全基因组测序分析,测定该菌发酵乳的ACE抑制活性,并采用正交实验优化发酵条件。【结果】渤海沉积物中含有乳杆菌并成功筛选出一株瑞士乳杆菌GY-3,其发酵乳具有较高的ACE抑制活性。该菌在发酵温度37°C,接种量3%,且在脱脂乳培养基中添加1.0%葡萄糖,0.6%大豆蛋白胨,1.0%酵母浸粉,0.04%MnSO_4·4H_2O时,抑制活性最高,可达79.52%。通过对该菌基因组进行测序研究,发现其产ACE抑制肽涉及蛋白酶系统、多肽转运系统和肽酶系统。【结论】为扩大海洋源产ACE抑制肽的乳杆菌种质资源、开发高产ACE抑制活性的发酵菌株奠定了基础,进一步研究了如何提高乳杆菌产ACE抑制肽的水平,并对其基因组进行了研究,为今后生物学特性和ACE抑制活性机理的研究奠定了基础,并对降血压相关产品的开发具有重要意义。     

Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice

Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2^-/-) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2^-/- mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2^-/- mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2^-/- mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2^-/- mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury.     

Endogenous inhibitor of angiotensin converting enzyme in the rat heart

We have identified a substance in the rat heart which inhibits ACE. This substance was characterized to be a sulfhydryl (SH) protein, the SH moiety being essential for the inhibitory activity. The inhibitory activity disappeared when the extract was boiled, or the ultrafiltrate(mol.wt.less than 10,000) was used, or when the extract was pretreated with the SH-blocking agent 5,5'-dithiobis-(2-nitro benzoic acid) at 0.5mM or the SH oxidizing agent diamide at 1mM. This substance was fractionated with Thiopropyl Sepharose affinity chromatography, precipitation with 40% ammonium sulfate saturation and high performance liquid chromatography. The mode of inhibition was competitive. In the presence of 20 micrograms/ml of this substance, the contraction of rat aortic strips induced by 5 x 10(-8)M ANG I was inhibited by 60%. This endogenous inhibitor of ACE may modulate the activity of ACE in the heart, in response to alterations in the oxidation-reduction balance in the tissue.     

Modulation of angiotensin-converting enzyme in cultured human vascular endothelial cells

Summary Previous work has suggested that not all immunoreactive angiotensin-converting enzyme (ACE) in tissues or cells is in a biologically active state. We have explored this possibility in cultured human umbilical vein endothelial cells (HUVEC), one of the most widely studied in vitro endothelial cell systems. Our approach included characterization of the effect of increasing passage number on ACE activity and expression of immunoreactive ACE at the single cell level, the subcellular compartmentalization of active ACE, and the effect of phorbol ester (PMA) treatment. We found that both ACE activity and expression of ACE antigen were downregulated by cultivation (30% of ACE-positive cells at seventh passage vs. 90% in primary culture). ACE downregulation is specific (number of CD31-positive cells did not change with cultivation) and correlated with downregulation of factor VIII-antigen. The percentage of ACE-positive cells in permeabilized HUVEC at third passage was almost twice that in nonpermeabilized HUVEC (90% vs. 50%), indicating that HUVEC contain intracellular immunoreactive ACE. ACE activity, however, was similar when measured in intact cells and in cell lysates. Moreover, diazonium salt of sulfanilic acid (DASA), a membrane-impermeable ACE inhibitor, inhibited ACE activity in intact cells and in cell lysates at the same extent, thus implying that intracellular ACE is inactive. PMA (100 nM) treatment increased the percentage of ACE-positive cells at third passage from 57 to 96%. ACE activity was increased 3-fold in cell and 1.5-fold in the culture medium of PMA-treated cells. Analysis of ACE activity in intact monolayers and cell lysates of control and PMA-treated cells revealed that all enzymatically active ACE in PMA-treated cells is localized on the plasma membrane and acts as an ectoenzyme. We conclude that expression of ACE by HUVEC is downregulated by repeated passage in culture but can be restored by PMA treatment. In addition, ACE expression is heterogeneous between neighboring cells, and total immunoreactive ACE protein associated with HUVEC includes an inactive pool of the enzyme.     

Genotoxicity of fractionated organic material in airborne particles from São Paulo, Brazil

Particulate matter less than 10 microns aerodynamic diameter (PM10) is associated with adverse health effects including increased respiratory problems and mortality. PM10 is also associated with increases in cancer in some urban areas. Identification of toxic compounds in PM10 is a step toward estimating exposure to these compounds and evaluating their public health risk. However, the toxic compounds on PM10 are part of a highly complex mixture of compounds that makes chemical characterization difficult. Before this study, there has been little investigation of genotoxic compounds in particulate matter from Latin American cities. Here, both bioassay (mutagenicity) and chemical analyses were conducted with organic solvent extracts of PM10 collected from S?o Paulo, a major Brazilian city. Sequential extraction in dichloromethane (DCM) followed by acetone (ACE) yielded 20.3% and 10.2% of the total mass, respectively. Non-polar and moderately polar organic material solubilized in DCM. ACE extracted more polar organic species and some inorganic ions. Both extracts were fractionated separately using cyanopropyl-bonded silica chromatography with organic solvents of increasing polarity. The mass distribution among the fractions was measured. The mutagenic activity of the fractions was assayed using the microsuspension procedure with the Salmonella typhimurium tester strain TA98, with and without addition of metabolic enzymes (S9). The DCM extract had about four times higher mutagenic activity than the ACE extract. In general, addition of S9 resulted in an increase in mutagenicity of DCM fractions, but a decrease for the ACE extract. Most of the activity was concentrated in fractions in the mid-range of polarity within both the DCM and ACE extracts. The fractions were analyzed by gas chromatography with mass selective detection (GC/MS) without derivatization. The most mutagenic fractions in the DCM extract contained ketones, aldehydes, and quinolines. The most mutagenic ACE fraction had ketones, carboxylic acids, and aldehydes.     

Dietary Weight Loss Decreases Serum Angiotensin-Converting Enzyme Activity in Obese Adults

Objective: To study the effect of dietary weight loss, postural change, and an oral glucose load on serum angiotensin-converting enzyme (ACE) activity in obese adults. Research Methods and Procedures: Sixteen obese adult men and women with a mean body mass index of 35.7 ± 4.3 kg/m² were studied after 1 week on a maintenance energy lead-in diet and after 5 weeks on an identical but 40% reduced-energy diet provided by the General Clinical Research Center (GCRC). ACE activity was measured spectrophotometrically. Plasma renin activity and serum aldosterone were measured by radioimmunoassay. Results: All subjects lost weight, with a mean decrease in body weight of 7.0 ± 2.1 kg or 6 ± 3% of initial body weight (p < 0.00001). Systolic and diastolic blood pressure, supine plasma renin activity, and serum aldosterone levels decreased with weight loss (p < 0.05). Supine ACE activity decreased 23 ± 12% with weight loss (p < 0.00001). Standing ACE activity, which was significantly higher than supine ACE activity before and after weight loss (p < 0.05), also decreased 18 ± 17% with weight loss (p = 0.0007). A 75-g oral glucose load had no effect on serum ACE activity over a 3-hour period. Discussion: In obese adults, serum ACE activity declines with modest weight loss, increases with postural change, and is unaffected by an oral glucose load.     

Enhancement of neutral endopeptidase activity in SK-N-SH cells by green tea extract

Green tea extract (EFLA85942) is able to induce specifically the neutral endopeptidase (NEP) activity and to inhibit the proliferation of SK-N-SH cells; the angiotensin-converting enzyme (ACE) activity is not influenced under the same conditions. The treatment of the cells with arabinosylcytosine and green tea extract results in a strong enhancement of cellular NEP activity whereas cellular ACE activity was not changed significantly, indicating a green tea extract-specific regulation of NEP expression. Because of its role in the degradation of amyloid beta peptides this enzyme induction of NEP by long term treatment with green tea extract may have a beneficial effect regarding the prevention of forming amyloid plaques.     

Lipopolysaccharides decrease angiotensin converting enzyme activity expressed by cultured human endothelial cells.

Angiotensin converting enzyme (ACE) is present on endothelial cells and plays a role in regulating blood pressure in vivo by converting angiotensin I to angiotensin II and metabolizing bradykinin. Since ACE activity is decreased in vivo in sepsis, the ability of lipopolysaccharide (LPS) to suppress endothelial cell ACE activity was tested by culturing human umbilical vein endothelial cells (HUVEC) for 0-72 hr with or without LPS and then measuring ACE activity. ACE activity in intact HUVEC monolayers incubated with LPS (10 micrograms/ml) decreased markedly with time and was inhibited by 33%, 71%, and 76% after 24 hr, 48 hr, and 72 hr, respectively, when compared with control, untreated cells. The inhibitory effect of LPS was partially reversible upon removal of the LPS and further incubation in the absence of LPS. The LPS-induced decrease in ACE activity was dependent on the concentrations of LPS (IC50 = 15 ng/ml at 24 hr) and was detectable at LPS concentrations as low as 1 ng/ml. That LPS decreased the Vmax of ACE in the absence of cytotoxicity and without a change in Km suggests that LPS decreased the amount of ACE present on the HUVEC cell membrane. While some LPS serotypes (Escherichia coli 0111:B4 and 055:B5, S. minnesota) were more potent inhibitors of ACE activity than others (E. coli 026:B6 and S. marcescens), all LPS serotypes tested were inhibitory. These finding suggest that LPS decreases endothelial ACE activity in septic patients; in turn, this decrease in ACE activity may decrease angiotensin II production and bradykinin catabolism and thus play a role in the pathogenesis of septic shock.     

Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene

We utilized mice with homozygous disruption of angiotensin-converting enzyme (ACE) (-/-), mice with heterozygous deletion of ACE (+/-), and wild-type mice (+/+) to test the hypothesis that genetic variation in ACE modulates tissue and plasma angiotensin (ANG) II concentrations. With the use of ANG I as substrate, kidney, heart, and lung ACE activity was reduced 80% in -/- mice compared with +/+ mice. However, ANG II concentrations and ANG II-to-ANG I ratios in the kidney, heart, and lung did not differ among genotypes. In contrast, plasma ANG II concentrations in -/- mice were <2 fmol/ml, whereas plasma ANG I concentrations were extremely high (765 fmol/ml). Chymase activity was increased 14-fold in the kidney (P < 0.05) and 1.5-fold in the heart (P < 0.05) of -/- versus +/+ mice but did not differ among genotypes in the lung. ANG II formation from enzymes other than ACE and chymase contributed <2% of total ANG II formation in all genotypes. These data suggest that ACE is essential to ANG II formation in the vascular space, whereas chymase may provide an important mechanism in maintaining steady-state ANG II levels in tissue.     

Metabolism and subcellular localization of angiotensin converting enzyme in cultured human monocytes

The enhancement of monocyte ACE activity during culture by autologous T-lymphocytes was shown to be due to a stimulation of the rate of ACE synthesis. The rate of synthesis increased from 0.020 mU/10(6) monocytes/hr in monocytes cultured alone to 0.063 mU/10(6) monocytes/hr in monocytes co-cultured with T-lymphocytes. The presence of T-lymphocytes during culture did not alter the rate of ACE degradation observed in monocytes cultured alone. The ACE induced in monocytes by T-lymphocytes appears to be an ecto-enzyme. Brief exposure to diazosulfanilic acid (10(-3) M) and papain (250 micrograms/ml) reduced ACE activity 89% and 66%, respectively, without appreciably altering the activity of the cytosolic enzyme, lactate dehydrogenase.