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)

Xenobiotics metabolized in rat pulmonary tissue are often selectively cytotoxic to individual lung cell populations. A non-homogeneous distribution of xenobiotic biotransformation enzymes, e.g., cytochrome P-450 (P-450)- and glutathione (GSH)-associated enzymes, in rat lung tissue may underlie this observed cell-selective pneumotoxicity. To evaluate this hypothesis, the relative activities of P-450- and GSH-associated enzymes were measured in sonicated, freshly isolated preparations containing enriched complements of individual toxicant-sensitive lung cell types, including non-ciliated bronchiolar epithelial (Clara) cells (24% pure), alveolar type II cells (86% pure) and pulmonary endothelial cells (identified by membrane-associated angiotensin converting enzyme activity). Lung cell fractions were isolated by centrifugal elutriation from male F344 rats that 48 h earlier received a single i.p. injection of either P-450-inducer beta-naphthoflavone (50 mg beta-NF/kg body weight) or corn oil vehicle. The enriched Clara cell fraction possessed (per 10(6) cells) greater P-450 and reduced GSH contents and higher enzyme activities (i.e., NADPH- and NADH cytochrome c reductases, benzyloxy (BROD)-, pentoxy (PROD)- and etoxyresorufin (EROD)-O-dealkylases, GSH transferase, GSH peroxidase, GSH reductase and NADPH quinone oxidoreductase) than either the enriched type II cell or endothelial cell preparations. However, the relative biochemical activities for the enriched fractions (Clara greater than type II greater than endothelial) generally reflected respective sonicate cellular protein content. Treatment of rats with beta-NF resulted in: (a) an induction in EROD activity in the enriched preparations of type II cells, Clara cells and endothelial cells (125-, 89- and 35-fold, respectively); (b) higher NADPH quinone oxidoreductase activities, which were increased to the greatest degree (3-fold) in the enriched type II cell fraction and (c) a small elevation in GSH transferase activity measured in the enriched Clara cell fraction. Although the enriched rat lung cell preparations possessed unique biochemical profiles for constitutive and beta-NF-inducible P-450- and GSH-associated enzymes, additional studies with higher purity preparations (e.g., Clara cells) will be required to more fully evaluate the relationship between relative cellular complements of xenobiotic biotransformation enzymes and pneumotoxicant susceptibility.
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PMID:Cytochrome P-450- and glutathione-associated enzyme activities in freshly isolated enriched lung cell fractions from beta-naphthoflavone-treated male F344 rats. 160 25

Changes in the levels of aldosterone synthase cytochrome P-450, a recently identified enzyme in rat adrenals, were studied in response to the renin-angiotensin system and K stimuli. As examined by an immunoblot technique, the zona glomerulosa mitochondria from rats fed on a low Na-normal K diet (8.6 mmol Na+ and 207 mmol K+/kg of diet) or a low Na-high K (0.2 M KCl in drinking water) diet for 4-10 days contained significantly higher amounts of aldosterone synthase cytochrome P-450 than those from rats fed on a normal diet (86 mmol Na+ and 207 mmol K+/kg of diet). Activities of the enzyme were also found to increase by about 10-fold on day 10. In concert with these changes, both plasma renin activity and plasma aldosterone concentration increased, indicating that the renin-angiotensin system was activated in these rats. Feeding with a normal Na-high K diet also induced significantly higher levels of both amount and activity of aldosterone synthase cytochrome P-450 together with an elevated serum K concentration on day 4, though they all decreased to near the control level on the following days. On the other hand, when enalapril malate, an angiotensin I-converting enzyme inhibitor, was administered to the low Na-normal K rats, the increases in the amount and activity of the enzyme as well as in plasma aldosterone concentration were suppressed altogether. However, the enalapril administration to the low Na-high K rats suppressed the increases only partially. These results indicate that the aldosterone synthase cytochrome P-450 is an ultimate target of the regulation of aldosterone biosynthesis by angiotensin II and K.
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PMID:Regulation of aldosterone synthase cytochrome P-450 in rat adrenals by angiotensin II and potassium. 201 65

Autoantibodies are important diagnostic markers for autoimmune type chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). At least three subgroups of AI-CAH can be distinguished serologically. Antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and liver membrane autoantibodies (LMA) characterize classical autoimmune type 'lupoid' hepatitis, while liver kidney microsomal (LKM) antibodies identify a second, and antibodies to a soluble liver antigen (anti-SLA), a third subgroup of AI-CAH. Patients with autoimmune type CAH in contrast to patients with virus-induced liver diseases profit from immunosuppressive therapy. PBC is characterized by disease-specific subtypes of antimitochondrial antibodies (AMA). Technical developments, like immunoblotting and molecular cloning, led to a better definition and characterization of autoantibody-antigen systems. Molecular cloning has been successfully applied to identify the main 70 kDa mitochondrial antigen in PBC. This and other mitochondrial autoantigens have been identified as enzymes: E2 component of pyruvate dehydrogenase (PDH-E2) and its component X, branched chain alpha-keto acid dehydrogenase (BCKD-E2), and 2-oxoglutarate dehydrogenase. LKM-1 antigen has been identified as cytochrome P-450 db1, a drug metabolizing enzyme with a known genetic polymorphism. These cloned hepatic autoantigens share some characteristics with other autoantigens: they are enzymes, autoantibodies react with active sites of these enzymes and the autoepitopes are highly conserved. After the identification of these autoepitopes, specific and sensitive diagnostic reagents will become available. B and T cell epitope mapping will help to elucidate whether these autoantibodies are just clinically valuable diagnostic markers or whether they contribute to the immunopathogenesis or help to identify the aetiological agents.
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PMID:Autoantibodies and antigens in liver diseases--updated. 268 96

Chlorophenols, mainly used as biocides, are compounds with a wide spectrum of toxic effects including teratogenic and carcinogenic actions. In this study, the effects of 2,4-dichlorophenol (2,4-DCP) on hepatic microsomal cytochrome P-450, NADPH-cytochrome c reductase activity, liver ascorbic acid (AA) and glutathione (GSH) content were studied in guinea-pigs with a low (2 mg/day/animal) or a high (50 mg/day/animal) ascorbic acid intake. The high AA intake significantly increased liver AA and GSH levels. There was a clear-cut correlation between liver AA and GSH levels. Administration of 2,4-DCP significantly decreased cytochrome P-450 and NADPH-cytochrome c reductase activity in hepatic microsomes isolated from guinea-pigs with the low AA intake. Such a reduction was not observed in intoxicated guinea-pigs with the high AA intake. The results suggest that AA can play a protective role in 2,4-DCP toxicity.
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PMID:The influence of ascorbic acid on the hepatic cytochrome P-450, and glutathione in guinea-pigs exposed to 2,4-dichlorophenol. 886 64

It is known that coadministration of a statin and certain drugs that inhibit cytochrome P-450 may inhibit catabolism of statin, resulting in an increased concentration of statin in the blood and consequently, increased risk of certain side effects, e.g. myopathy. The aim of this study was to establish, for the first time, how many patients in Croatia concomitantly take statins with other drugs, and which drugs. Also, the aim was to determine how often statins are administered concomitantly with cytochrome P-450 inhibitors, and how many patients taking statin are therefore at increased risk of interactions and/or side effects. The data were collected from general practitioners' health records all over Croatia during July and August 2004. The data for patients who were prescribed any statin between June 1, 2003 and June 1, 2004 were analysed. The records of 882 patients were analysed, 446 (50.6%) women, 422 (47.8%) men and 14 (1.6%) of unidentified sex. The average age of women on statin was 65 years and of men 60 years. Of 882 patients, 772 patients (82%) were taking at least one more drug concurrently with statin. Of that number, 24% of patients concomitantly were taking one more drug, 20% two more drugs, 16% three more drugs, 10% four more drugs, 8% five more drugs and 3% six more drugs. The average number of other drugs prescribed together with statin was 2.1 +/- 1.59 in men and 2.2 +/- 1.71 in women. The average age of patients who were taking another drug together with a statin did not significantly differ from that of patients receiving only statin. There were regional differences in the number of drugs prescribed together with a statin. In Osijek, the average number of drugs prescribed with a statin was 2.4 +/- 1.80, in Zagreb 2.2 +/- 1.64, in Rijeka 2.0 +/- 1.60, and in Split 1.8 +/- 1.44. The number of drugs prescribed with a statin in rural areas was 2.0 +/- 1.58, in urban areas 2.1 +/- 1.63 and in semi-urban areas 2.8 +/- 1.85. The therapeutic groups of drugs that are most frequently prescribed with a statin in Croatia are ACE inhibitors and their fixed combinations (32%), beta-receptor blockers and their fixed combinations (23%), selective calcium channel blockers (18%), anxiolytics (18%), vasodilators and organic nitrates (16%), antirheumatic drugs (11%), oral antidiabetics (11%), vitamin K antagonists, analgesics-antipyretics, diuretics (10%), antibiotics (8%), and angiotensin II antagonists and their fixed combinations (5%). All other drugs accounted for less than 5%. Four percent of the patients take cytochrome P-450 inhibitors concomitantly with a statin. The most frequently used drug is verapamil, combination of verapamil and trandolapril, clarithromycin and diltiazem. Consequently, 3% of men and 5% of women are at increased risk of side effects. This sex difference is, however, not statistically significant. Patients between 70 and 74 years of age taking statins are in Croatia at the highest risk of interactions because 8% of them take concomitantly cytochrome P 450 inhibitors.
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PMID:[Concomitant use of statins and cytochrome P 450 inhibitors in Croatia]. 1619 55

20-Hydroxyeicosatetraenoic acid (20-HETE) is an important metabolite of cytochrome P-450 pathway of arachidonic acid (AA). It has been demonstrated recently that 20-HETE played a significant role in physiology and pathophysiology process of vascular endothelium (EC). 20-HETE exerted oxidative stress and pro-inflammation effect through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and nuclear factor-kappaB (NF-kappaB) pathway; it took part in the modulation of vascular dilation and constriction by mediating dissociation of endothelial nitric oxide synthase (eNOS) and inducing angiotensin converting enzyme in EC; it also promoted the proliferation of EC and angiogenesis. However, the domestic study about 20-HETE is rare. Therefore, the present paper reviewed the recent international studies of 20-HETE on EC.
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PMID:[Progress of studies in 20-hydroxyeicosatetraenoic acid on vascular endothelium]. 2367 92